Phase I AZD2281/Cisplatin in Advanced Solid Tumour participants

Study identifier:D0810C00021

ClinicalTrials.gov identifier:NCT00782574

EudraCT identifier:2008-000062-24

CTIS identifier:N/A

Study Complete

Official Title

A Phase I Open label, Multi centre study of AZD2281 Administered Orally in combination With Cisplatin, to assess the Safety and Tolerability in Patients with Advanced Solid Tumours

Medical condition

Advanced Solid Tumors

Phase

Phase 1

Healthy volunteers

Study drug

AZD2281, Cisplatin

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 99 Years

Date

Study Start Date: 12 Nov 2008

Primary Completion Date: 01 Feb 2012

Study Completion Date: 07 Dec 2023

Study design

Allocation: Non-randomized
Endpoint Classification: Safety
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment

Verification:

Verified 01 Dec 2024 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Location

Research Site

Barcelona, Spain, 8035

Location

Research Site

Boston, MA, United States, 02215

Location

Research Site

Boston, MA, United States, 02114

Location

Research Site

Boston, MA, United States, 02115

Arms	Assigned Interventions
Experimental: Cohort 1: Continuous Dosing Participants will receive oral olaparib capsule 50 mg once on Study Day 1 and thereafter will receive combination therapy of oral olaparib capsule 50 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants will continue receiving oral olaparib 50 mg BID until Day 21 of the cycle. Participants will continue receiving combination therapy until Cycle 6 or until they receive benefit and are free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants will continue receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants receive benefit or not met disease progression or any other discontinuation criteria.	Drug: AZD2281 Participants will receive oral olaparib capsule as stated in arm description. Other Name: Olaparib; Lynparza Drug: Cisplatin Participants will receive IV infusion of cisplatin as stated in arm description.
Experimental: Cohort 2: Continuous Dosing Participants will receive oral olaparib capsule 100 mg once on Study Day 1 and thereafter will receive combination therapy of oral olaparib capsule 100 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants will continue receiving oral olaparib 100 mg BID until Day 21 of the cycle. Participants will continue receiving combination therapy until Cycle 6 or until they receive benefit and are free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants will continue receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants receive benefit or not met disease progression or any other discontinuation criteria.	Drug: AZD2281 Participants will receive oral olaparib capsule as stated in arm description. Other Name: Olaparib; Lynparza Drug: Cisplatin Participants will receive IV infusion of cisplatin as stated in arm description.
Experimental: Cohort 3: Continuous Dosing Participants will receive oral olaparib capsule 200 mg once on Study Day 1 and thereafter will receive combination therapy of oral olaparib capsule 200 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants will continue receiving oral olaparib 200 mg BID until Day 21 of the cycle. Participants will continue receiving combination therapy until Cycle 6 or until they receive benefit and are free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants will continue receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants receive benefit or not met disease progression or any other discontinuation criteria.	Drug: AZD2281 Participants will receive oral olaparib capsule as stated in arm description. Other Name: Olaparib; Lynparza Drug: Cisplatin Participants will receive IV infusion of cisplatin as stated in arm description.
Experimental: Cohort 4: Intermittent Dosing Participants will receive oral olaparib capsule 100 mg BID on Days 1 to 10 and IV cisplatin infusion 75 mg/m^2 on Day 1 of 21-day cycle. Participants will continue receiving combination therapy until Cycle 6 or until they receive benefit and are free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants will continue receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants receive benefit or not met disease progression or any other discontinuation criteria.	Drug: AZD2281 Participants will receive oral olaparib capsule as stated in arm description. Other Name: Olaparib; Lynparza Drug: Cisplatin Participants will receive IV infusion of cisplatin as stated in arm description.
Experimental: Cohort 5: Intermittent Dosing Participants will receive oral olaparib capsule 50 mg BID on Days 1 to 10 and IV cisplatin infusion 75 mg/m^2 on Day 1 of 21-day cycle. Participants will continue receiving combination therapy until Cycle 6 or until they receive benefit and are free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants will continue receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants receive benefit or not met disease progression or any other discontinuation criteria.	Drug: AZD2281 Participants will receive oral olaparib capsule as stated in arm description. Other Name: Olaparib; Lynparza Drug: Cisplatin Participants will receive IV infusion of cisplatin as stated in arm description.
Experimental: Cohort 6: Intermittent Dosing Participants will receive oral olaparib capsule 50 mg BID on Days 1 to 10 and IV cisplatin infusion 60 mg/m^2 on Day 1 of 21-day cycle. Participants will continue receiving combination therapy until Cycle 6 or until they receive benefit and are free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants will continue receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants receive benefit or not met disease progression or any other discontinuation criteria.	Drug: AZD2281 Participants will receive oral olaparib capsule as stated in arm description. Other Name: Olaparib; Lynparza Drug: Cisplatin Participants will receive IV infusion of cisplatin as stated in arm description.

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was conducted at 4 sites in 2 countries (the United States and Spain).

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 59 participants were enrolled in the study, out of which only 54 participants received treatment. Out of 59 enrolled, four participants were incorrectly enrolled and one participant was excluded due to the investigator’s decision.

Reporting Groups

	Description
Cohort 1: Continuous Dosing	Participants received oral olaparib capsule 50 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 50 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 50 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 2: Continuous Dosing	Participants received oral olaparib capsule 100 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 100 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 100 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 3: Continuous Dosing	Participants received oral olaparib capsule 200 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 200 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 200 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 4: Intermittent Dosing	Participants received oral olaparib capsule 100 mg BID on Days 1 to 10 and IV cisplatin infusion 75 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 5: Intermittent Dosing	Participants received oral olaparib capsule 50 mg BID on Days 1 to 10 and IV cisplatin infusion 75 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 6: Intermittent Dosing	Participants received oral olaparib capsule 50 mg BID on Days 1 to 10 and IV cisplatin infusion 60 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.

Participant Flow: Overall Study

	Cohort 1: Continuous Dosing	Cohort 2: Continuous Dosing	Cohort 3: Continuous Dosing	Cohort 4: Intermittent Dosing	Cohort 5: Intermittent Dosing	Cohort 6: Intermittent Dosing
STARTED	3	13	6	14	6	12
COMPLETED	0	0	0	0	0	0
NOT COMPLETED	3	13	6	14	6	12
Not specified	0	0	0	1	0	0
Condition under investigation worsened	1	11	4	12	5	6
Adverse Event	0	2	2	0	0	0
Ongoing study at data cutoff	2	0	0	1	1	6

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Full analysis set included all participants who received at least one dose of study drug.

Reporting Groups

	Description
Cohort 1: Continuous Dosing	Participants received oral olaparib capsule 50 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 50 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 50 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 2: Continuous Dosing	Participants received oral olaparib capsule 100 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 100 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 100 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 3: Continuous Dosing	Participants received oral olaparib capsule 200 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 200 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 200 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 4: Intermittent Dosing	Participants received oral olaparib capsule 100 mg BID on Days 1 to 10 and IV cisplatin infusion 75 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 5: Intermittent Dosing	Participants received oral olaparib capsule 50 mg BID on Days 1 to 10 and IV cisplatin infusion 75 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 6: Intermittent Dosing	Participants received oral olaparib capsule 50 mg BID on Days 1 to 10 and IV cisplatin infusion 60 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.

Baseline Measures

	Cohort 1: Continuous Dosing	Cohort 2: Continuous Dosing	Cohort 3: Continuous Dosing	Cohort 4: Intermittent Dosing	Cohort 5: Intermittent Dosing	Cohort 6: Intermittent Dosing	Total
Number of Participants [units: Participants]	3	13	6	14	6	12	54
Age Continuous [units: Years] Mean ± Standard Deviation	50.7 ± 12.0	49.2 ± 10.8	53.2 ± 14.9	47.7 ± 9.3	49.7 ± 9.6	48.3 ± 11.0	49.2 ± 10.5
Sex: Female, Male [units: Participants]
Female	3	13	6	14	6	10	52
Male	0	0	0	0	0	2	2
Race (NIH/OMB) [units: Participants]
American Indian or Alaska Native	0	0	0	0	0	0	0
Asian	0	1	0	0	0	0	1
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0
Black or African American	0	0	0	0	0	0	0
White	3	12	6	14	6	12	53
More than one race	0	0	0	0	0	0	0
Unknown or Not Reported	0	0	0	0	0	0	0
Ethnicity (NIH/OMB) [units: Participants]
Hispanic or Latino	0	0	0	0	0	0	0
Not Hispanic or Latino	0	0	0	0	0	0	0
Unknown or Not Reported	3	13	6	14	6	12	54

Outcome Measures

1. Primary Outcome Measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) [ Time Frame: Day 1 through Day 1181 (maximum observed duration) ]

Measure Type	Primary
Measure Name	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Measure Description	An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Time Frame	Day 1 through Day 1181 (maximum observed duration)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety analysis set included all participants who received at least one dose of olaparib.

Reporting Groups

	Description
Cohort 1: Continuous Dosing	Participants received oral olaparib capsule 50 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 50 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 50 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 2: Continuous Dosing	Participants received oral olaparib capsule 100 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 100 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 100 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 3: Continuous Dosing	Participants received oral olaparib capsule 200 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 200 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 200 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 4: Intermittent Dosing	Participants received oral olaparib capsule 100 mg BID on Days 1 to 10 and IV cisplatin infusion 75 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 5: Intermittent Dosing	Participants received oral olaparib capsule 50 mg BID on Days 1 to 10 and IV cisplatin infusion 75 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 6: Intermittent Dosing	Participants received oral olaparib capsule 50 mg BID on Days 1 to 10 and IV cisplatin infusion 60 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.

Measured Values

	Cohort 1: Continuous Dosing	Cohort 2: Continuous Dosing	Cohort 3: Continuous Dosing	Cohort 4: Intermittent Dosing	Cohort 5: Intermittent Dosing	Cohort 6: Intermittent Dosing
Number of Participants Analyzed [units:participants]	3	13	6	14	6	12
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) [units: Participants]
TEAEs	3	13	6	14	6	12
TESAEs	0	3	2	2	4	5

No statistical analysis provided for Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

2. Primary Outcome Measure: Number of Participants With Clinically Significant Abnormalities in Vital Signs [ Time Frame: Day 1 through Day 1181 (maximum observed duration) ]

Measure Type	Primary
Measure Name	Number of Participants With Clinically Significant Abnormalities in Vital Signs
Measure Description	Number of participants with clinically significant abnormalities in vital signs are reported. Clinically significant abnormal vital signs are defined as any significant abnormal finding in the vital sign parameters (blood pressure, pulse rate, and body temperature).
Time Frame	Day 1 through Day 1181 (maximum observed duration)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety analysis set included all participants who received at least one dose of olaparib.

Reporting Groups

	Description
Cohort 1: Continuous Dosing	Participants received oral olaparib capsule 50 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 50 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 50 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 2: Continuous Dosing	Participants received oral olaparib capsule 100 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 100 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 100 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 3: Continuous Dosing	Participants received oral olaparib capsule 200 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 200 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 200 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 4: Intermittent Dosing	Participants received oral olaparib capsule 100 mg BID on Days 1 to 10 and IV cisplatin infusion 75 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 5: Intermittent Dosing	Participants received oral olaparib capsule 50 mg BID on Days 1 to 10 and IV cisplatin infusion 75 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 6: Intermittent Dosing	Participants received oral olaparib capsule 50 mg BID on Days 1 to 10 and IV cisplatin infusion 60 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.

Measured Values

	Cohort 1: Continuous Dosing	Cohort 2: Continuous Dosing	Cohort 3: Continuous Dosing	Cohort 4: Intermittent Dosing	Cohort 5: Intermittent Dosing	Cohort 6: Intermittent Dosing
Number of Participants Analyzed [units:participants]	3	13	6	14	6	12
Number of Participants With Clinically Significant Abnormalities in Vital Signs [units: Participants]	0	0	0	0	0	0

No statistical analysis provided for Number of Participants With Clinically Significant Abnormalities in Vital Signs

3. Primary Outcome Measure: Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs [ Time Frame: Day 1 through Day 1181 (maximum observed duration) ]

Measure Type	Primary
Measure Name	Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs
Measure Description	Number of participants with abnormal ECG reported as TEAEs are reported.
Time Frame	Day 1 through Day 1181 (maximum observed duration)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety analysis set included all participants who received at least one dose of olaparib.

Reporting Groups

	Description
Cohort 1: Continuous Dosing	Participants received oral olaparib capsule 50 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 50 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 50 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 2: Continuous Dosing	Participants received oral olaparib capsule 100 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 100 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 100 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 3: Continuous Dosing	Participants received oral olaparib capsule 200 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 200 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 200 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 4: Intermittent Dosing	Participants received oral olaparib capsule 100 mg BID on Days 1 to 10 and IV cisplatin infusion 75 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 5: Intermittent Dosing	Participants received oral olaparib capsule 50 mg BID on Days 1 to 10 and IV cisplatin infusion 75 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 6: Intermittent Dosing	Participants received oral olaparib capsule 50 mg BID on Days 1 to 10 and IV cisplatin infusion 60 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.

Measured Values

	Cohort 1: Continuous Dosing	Cohort 2: Continuous Dosing	Cohort 3: Continuous Dosing	Cohort 4: Intermittent Dosing	Cohort 5: Intermittent Dosing	Cohort 6: Intermittent Dosing
Number of Participants Analyzed [units:participants]	3	13	6	14	6	12
Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs [units: Participants]	0	0	0	0	0	0

No statistical analysis provided for Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs

4. Primary Outcome Measure: Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs [ Time Frame: Day 1 through Day 1181 (maximum observed duration) ]

Measure Type	Primary
Measure Name	Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Measure Description	Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of haematology, clinical chemistry, and urinalysis
Time Frame	Day 1 through Day 1181 (maximum observed duration)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety analysis set included all participants who received at least one dose of olaparib.

Reporting Groups

	Description
Cohort 1: Continuous Dosing	Participants received oral olaparib capsule 50 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 50 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 50 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 2: Continuous Dosing	Participants received oral olaparib capsule 100 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 100 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 100 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 3: Continuous Dosing	Participants received oral olaparib capsule 200 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 200 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 200 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 4: Intermittent Dosing	Participants received oral olaparib capsule 100 mg BID on Days 1 to 10 and IV cisplatin infusion 75 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 5: Intermittent Dosing	Participants received oral olaparib capsule 50 mg BID on Days 1 to 10 and IV cisplatin infusion 75 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 6: Intermittent Dosing	Participants received oral olaparib capsule 50 mg BID on Days 1 to 10 and IV cisplatin infusion 60 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.

Measured Values

	Cohort 1: Continuous Dosing	Cohort 2: Continuous Dosing	Cohort 3: Continuous Dosing	Cohort 4: Intermittent Dosing	Cohort 5: Intermittent Dosing	Cohort 6: Intermittent Dosing
Number of Participants Analyzed [units:participants]	3	13	6	14	6	12
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs [units: Participants]
Anaemia	1	6	4	3	3	3
Hypoglobulinaemia	0	0	0	0	0	1
Leukocytosis	0	0	0	1	0	0
Leukopenia	1	6	0	5	0	0
Lymphopenia	1	1	0	3	0	1
Macrocytosis	0	0	1	0	0	0
Neutropenia	3	5	4	6	1	3
Thrombocytopenia	2	4	3	2	0	0
Thrombocytosis	0	1	0	0	0	0
Ketonuria	1	0	0	0	0	0
Proteinuria	1	1	0	1	0	0
Activated partial thromboplastin time prolonged	0	1	0	0	0	0
Activated partial thromboplastin time shortened	0	1	0	1	0	0
Alanine aminotransferase increased	1	3	0	1	1	3
Aspartate aminotransferase increased	0	1	0	0	0	1
Blood alkaline phosphatase increased	2	2	1	1	0	1
Blood amylase increased	1	0	0	1	0	0
Blood chloride decreased	0	0	0	1	0	0
Blood creatinine increased	0	1	0	0	1	0
Blood glucose increased	0	0	0	2	0	0
Blood lactate dehydrogenase increased	0	3	0	1	0	0
Blood phosphorus decreased	0	0	0	0	0	1
Blood potassium decreased	0	0	0	0	0	1
Blood urea increased	0	1	0	1	0	1
Blood urine present	0	0	0	1	0	0
Gamma-glutamyltransferase increased	0	3	0	0	0	1
Globulin	0	1	0	0	0	0
Globulins decreased	0	0	0	1	0	0
Glucose urine	0	0	0	1	0	0
Glucose urine present	0	0	0	0	0	1
International normalised ratio increased	0	1	0	0	0	0
Lipase	0	0	0	0	0	1
Lipase increased	0	0	1	2	0	0
Low density lipoprotein increased	0	0	0	1	0	0
Neutrophil count decreased	0	1	0	0	0	1
Neutrophil count increased	0	0	0	1	0	0
Protein total decreased	0	0	0	1	0	0
Protein urine present	0	0	0	2	0	0
Prothrombin time prolonged	0	1	0	0	0	0
Red blood cells urine	0	0	0	1	0	0
Red blood cells urine positive	0	0	0	1	0	0
Urinary sediment present	0	0	0	1	0	0
White blood cell count decreased	0	0	0	0	0	1
White blood cell count increased	0	2	0	1	0	1
White blood cells urine positive	0	1	0	2	0	0
Hypercholesterolaemia	0	1	0	1	0	0
Hyperglycaemia	0	3	1	1	0	1
Hyperkalaemia	1	0	0	0	0	0
Hyperphosphataemia	0	1	0	0	0	0
Hypertriglyceridaemia	0	1	0	0	0	0
Hypoalbuminaemia	0	0	0	1	0	0
Hypocalcaemia	0	0	0	1	0	0
Hypochloraemia	1	0	0	0	0	1
Hypokalaemia	1	0	1	1	0	0
Hypomagnesaemia	1	3	2	1	0	0
Hyponatraemia	1	0	0	1	0	1
Hypophosphataemia	0	0	1	0	0	1

No statistical analysis provided for Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs

5. Primary Outcome Measure: Number of Participants With Abnormality or Aggravation in Physical Examination [ Time Frame: Baseline (screening), at Weeks 2, 5, and 8, every week following Week 8, and at withdrawal, and 30-day follow-up ]

Measure Type	Primary
Measure Name	Number of Participants With Abnormality or Aggravation in Physical Examination
Measure Description	Number of participants with abnormality or aggravation in physical examination are reported.
Time Frame	Baseline (screening), at Weeks 2, 5, and 8, every week following Week 8, and at withdrawal, and 30-day follow-up
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety analysis set included all participants who received at least one dose of olaparib.

Reporting Groups

	Description
Cohort 1: Continuous Dosing	Participants received oral olaparib capsule 50 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 50 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 50 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 2: Continuous Dosing	Participants received oral olaparib capsule 100 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 100 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 100 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 3: Continuous Dosing	Participants received oral olaparib capsule 200 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 200 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 200 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 4: Intermittent Dosing	Participants received oral olaparib capsule 100 mg BID on Days 1 to 10 and IV cisplatin infusion 75 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 5: Intermittent Dosing	Participants received oral olaparib capsule 50 mg BID on Days 1 to 10 and IV cisplatin infusion 75 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 6: Intermittent Dosing	Participants received oral olaparib capsule 50 mg BID on Days 1 to 10 and IV cisplatin infusion 60 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.

Measured Values

	Cohort 1: Continuous Dosing	Cohort 2: Continuous Dosing	Cohort 3: Continuous Dosing	Cohort 4: Intermittent Dosing	Cohort 5: Intermittent Dosing	Cohort 6: Intermittent Dosing
Number of Participants Analyzed [units:participants]	3	13	6	14	6	12
Number of Participants With Abnormality or Aggravation in Physical Examination [units: Participants]	0	0	0	0	0	0

No statistical analysis provided for Number of Participants With Abnormality or Aggravation in Physical Examination

6. Secondary Outcome Measure: Percentage of Participants With Objective Response by Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Baseline (within 28 days pre-dose), end of every 2 cycles of treatment, at study withdrawal; for olaparib monotherapy at Weeks 9, 18, then every 12 weeks relative to Cycle 1 Day 1 of combination therapy until disease progression (approx. 15.1 years) ]

Measure Type	Secondary
Measure Name	Percentage of Participants With Objective Response by Response Evaluation Criteria in Solid Tumors (RECIST)
Measure Description	Objective response was defined as participants with a best response of complete response (CR) or partial response (PR) based on RECIST assessment response. The CR is defined as disappearance of all target and non-target lesions and no new lesions. The PR is defined as >=30% decrease in the sum of the diameters of target lesions compared to baseline and no new non-target lesion. Percentage of participants with objective response was reported.
Time Frame	Baseline (within 28 days pre-dose), end of every 2 cycles of treatment, at study withdrawal; for olaparib monotherapy at Weeks 9, 18, then every 12 weeks relative to Cycle 1 Day 1 of combination therapy until disease progression (approx. 15.1 years)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set included all participants who received at least one dose of study drug. Here, number of participants analyzed denotes those participants who had target tumour at baseline and were evaluable for RECIST response.

Reporting Groups

	Description
Cohort 1: Continuous Dosing	Participants received oral olaparib capsule 50 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 50 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 50 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 2: Continuous Dosing	Participants received oral olaparib capsule 100 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 100 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 100 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 3: Continuous Dosing	Participants received oral olaparib capsule 200 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 200 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 200 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 4: Intermittent Dosing	Participants received oral olaparib capsule 100 mg BID on Days 1 to 10 and IV cisplatin infusion 75 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 5: Intermittent Dosing	Participants received oral olaparib capsule 50 mg BID on Days 1 to 10 and IV cisplatin infusion 75 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 6: Intermittent Dosing	Participants received oral olaparib capsule 50 mg BID on Days 1 to 10 and IV cisplatin infusion 60 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.

Measured Values

	Cohort 1: Continuous Dosing	Cohort 2: Continuous Dosing	Cohort 3: Continuous Dosing	Cohort 4: Intermittent Dosing	Cohort 5: Intermittent Dosing	Cohort 6: Intermittent Dosing
Number of Participants Analyzed [units:participants]	3	12	4	10	6	11
Percentage of Participants With Objective Response by Response Evaluation Criteria in Solid Tumors (RECIST) [units: Percentage of Participants] Number (95% Confidence Interval)	100 (NA to NA) ^[1]	0 (0.0 to 24.2)	75.0 (NA to NA) ^[1]	50.0 (23.7 to 76.3)	50.0 (NA to NA) ^[1]	45.5 (21.3 to 72.0)

No statistical analysis provided for Percentage of Participants With Objective Response by Response Evaluation Criteria in Solid Tumors (RECIST)

7. Secondary Outcome Measure: Duration of Objective Response [ Time Frame: Baseline (within 28 days pre-dose), end of every 2 cycles of treatment, at study withdrawal; for olaparib monotherapy at Weeks 9, 18, then every 12 weeks relative to Cycle 1 Day 1 of combination therapy until disease progression (approx. 15.1 years) ]

Measure Type	Secondary
Measure Name	Duration of Objective Response
Measure Description	Duration of objective response was defined as the time from the initial assessment prior of PR or CR (the assessment prior to being a confirmed response), until the earliest date of objective disease progression or death. The median duration of response was derived from Kaplan Meier analysis. Responses were still ongoing in Cohorts 1, 4, 5, and 6 at data cut-off.
Time Frame	Baseline (within 28 days pre-dose), end of every 2 cycles of treatment, at study withdrawal; for olaparib monotherapy at Weeks 9, 18, then every 12 weeks relative to Cycle 1 Day 1 of combination therapy until disease progression (approx. 15.1 years)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set included all participants who received at least one dose of study drug. Here, number of participants analyzed denotes those participants who had objective response.

Reporting Groups

	Description
Cohort 1: Continuous Dosing	Participants received oral olaparib capsule 50 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 50 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 50 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 2: Continuous Dosing	Participants received oral olaparib capsule 100 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 100 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 100 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 3: Continuous Dosing	Participants received oral olaparib capsule 200 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 200 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 200 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 4: Intermittent Dosing	Participants received oral olaparib capsule 100 mg BID on Days 1 to 10 and IV cisplatin infusion 75 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 5: Intermittent Dosing	Participants received oral olaparib capsule 50 mg BID on Days 1 to 10 and IV cisplatin infusion 75 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 6: Intermittent Dosing	Participants received oral olaparib capsule 50 mg BID on Days 1 to 10 and IV cisplatin infusion 60 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.

Measured Values

	Cohort 1: Continuous Dosing	Cohort 2: Continuous Dosing	Cohort 3: Continuous Dosing	Cohort 4: Intermittent Dosing	Cohort 5: Intermittent Dosing	Cohort 6: Intermittent Dosing
Number of Participants Analyzed [units:participants]	3	0	3	5	3	5
Duration of Objective Response [units: Days] Median (Full Range)	NA (88 to 1092) ^[1]		316 (41 to 887)	133 (91 to 694)	307 (179 to 388)	162 (83 to 245)

No statistical analysis provided for Duration of Objective Response

8. Secondary Outcome Measure: Time to Onset of Objective Response [ Time Frame: Baseline (within 28 days pre-dose), end of every 2 cycles of treatment, at study withdrawal; for olaparib monotherapy at Weeks 9, 18, then every 12 weeks relative to Cycle 1 Day 1 of combination therapy until disease progression (approx. 15.1 years) ]

Measure Type	Secondary
Measure Name	Time to Onset of Objective Response
Measure Description	Onset of response was defined as the time interval from first taking study drug to the assessment when CR or PR was first observed, providing it was subsequently confirmed. The median time to onset response was derived from Kaplan Meier analysis.
Time Frame	Baseline (within 28 days pre-dose), end of every 2 cycles of treatment, at study withdrawal; for olaparib monotherapy at Weeks 9, 18, then every 12 weeks relative to Cycle 1 Day 1 of combination therapy until disease progression (approx. 15.1 years)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set included all participants who received at least one dose of study drug. Here, number of participants analyzed denotes those participants who had objective response.

Reporting Groups

	Description
Cohort 1: Continuous Dosing	Participants received oral olaparib capsule 50 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 50 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 50 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 2: Continuous Dosing	Participants received oral olaparib capsule 100 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 100 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 100 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 3: Continuous Dosing	Participants received oral olaparib capsule 200 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 200 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 200 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 4: Intermittent Dosing	Participants received oral olaparib capsule 100 mg BID on Days 1 to 10 and IV cisplatin infusion 75 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 5: Intermittent Dosing	Participants received oral olaparib capsule 50 mg BID on Days 1 to 10 and IV cisplatin infusion 75 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 6: Intermittent Dosing	Participants received oral olaparib capsule 50 mg BID on Days 1 to 10 and IV cisplatin infusion 60 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.

Measured Values

	Cohort 1: Continuous Dosing	Cohort 2: Continuous Dosing	Cohort 3: Continuous Dosing	Cohort 4: Intermittent Dosing	Cohort 5: Intermittent Dosing	Cohort 6: Intermittent Dosing
Number of Participants Analyzed [units:participants]	3	0	3	5	3	5
Time to Onset of Objective Response [units: Days] Median (Full Range)	128 (41 to 172)		46 (35 to 48)	49 (44 to 101)	40 (38 to 84)	56 (35 to 96)

No statistical analysis provided for Time to Onset of Objective Response

9. Secondary Outcome Measure: Best Percentage Change From Baseline in Target Lesion Size [ Time Frame: For combination therapy at baseline (up to 28 days prior to Study Day 1), Day 50, and at time of withdrawal; for olaparib monotherapy at Weeks 9, 18, thereafter every 12 weeks relative to Cycle 1 Day 1 of combination therapy until disease progression ]

Measure Type	Secondary
Measure Name	Best Percentage Change From Baseline in Target Lesion Size
Measure Description	The total tumor size was defined as the sum of the longest diameter of the target lesions. Best change in target lesion size is the maximum reduction from baseline or minimum increase in the absence of a reduction. The percentage change in total tumor (target lesion) size at each scheduled visit was calculated as the [(visit sum target lesions – baseline sum of target lesions)/baseline sum target lesions]*100. A negative change denotes a reduction in target lesion size.
Time Frame	For combination therapy at baseline (up to 28 days prior to Study Day 1), Day 50, and at time of withdrawal; for olaparib monotherapy at Weeks 9, 18, thereafter every 12 weeks relative to Cycle 1 Day 1 of combination therapy until disease progression
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set included all participants who received at least one dose of study drug. Number of participants analyzed denotes the number of participants evaluated for this outcome measure.

Reporting Groups

	Description
Cohort 1: Continuous Dosing	Participants received oral olaparib capsule 50 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 50 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 50 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 2: Continuous Dosing	Participants received oral olaparib capsule 100 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 100 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 100 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 3: Continuous Dosing	Participants received oral olaparib capsule 200 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 200 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 200 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 4: Intermittent Dosing	Participants received oral olaparib capsule 100 mg BID on Days 1 to 10 and IV cisplatin infusion 75 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 5: Intermittent Dosing	Participants received oral olaparib capsule 50 mg BID on Days 1 to 10 and IV cisplatin infusion 75 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 6: Intermittent Dosing	Participants received oral olaparib capsule 50 mg BID on Days 1 to 10 and IV cisplatin infusion 60 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.

Measured Values

	Cohort 1: Continuous Dosing	Cohort 2: Continuous Dosing	Cohort 3: Continuous Dosing	Cohort 4: Intermittent Dosing	Cohort 5: Intermittent Dosing	Cohort 6: Intermittent Dosing
Number of Participants Analyzed [units:participants]	3	12	4	10	6	11
Best Percentage Change From Baseline in Target Lesion Size [units: Percent Change in Lesion Size] Mean (Standard Deviation)	-56.9 (16.34)	-6.1 (21.95)	-52.2 (31.21)	-32.5 (27.32)	-39.3 (29.48)	-21.0 (36.94)

No statistical analysis provided for Best Percentage Change From Baseline in Target Lesion Size

10. Secondary Outcome Measure: Plasma Concentration of Olaparib [ Time Frame: Predose, 1, 2, 3, 4, 6, 8, and 12 hours post dose on V2 (Study Day 1) and V3 (Study Day 8) ]

Measure Type	Secondary
Measure Name	Plasma Concentration of Olaparib
Measure Description	Plasma concentration of olaparib at Visit (V) 2 (Study Day 1) and 3 (Study Day 8) is reported.
Time Frame	Predose, 1, 2, 3, 4, 6, 8, and 12 hours post dose on V2 (Study Day 1) and V3 (Study Day 8)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic (PK) analysis set included subset of safety analysis set including participants who had reportable PK data for olaparib both alone at Visit 2 and in combination with cisplatin at Visit 3. Number analyzed (n) denotes those participants who were evaluable at the specified time point.

Reporting Groups

	Description
Cohort 1: Continuous Dosing	Participants received oral olaparib capsule 50 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 50 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 50 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 2: Continuous Dosing	Participants received oral olaparib capsule 100 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 100 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 100 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 3: Continuous Dosing	Participants received oral olaparib capsule 200 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 200 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 200 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.

Measured Values

	Cohort 1: Continuous Dosing	Cohort 2: Continuous Dosing	Cohort 3: Continuous Dosing
Number of Participants Analyzed [units:participants]	3	12	6
Plasma Concentration of Olaparib [units: μg/mL] Geometric Mean (Geometric Coefficient of Variation)
V2: 1 hour	0.591 (176.200%)	1.404 (198.200%)	1.640 (86.440%)
V2: 2 hours	1.168 (150.200%)	2.439 (91.100%)	3.080 (29.990%)
V2: 3 hours	0.669 (169.400%)	2.213 (104.400%)	2.769 (36.610%)
V2: 4 hours	0.430 (161.500%)	1.864 (128.200%)	2.113 (47.280%)
V2: 6 hours	0.222 (110.300%)	1.208 (176.200%)	1.277 (54.360%)
V2: 8 hours	0.117 (111.100%)	0.754 (200.400%)	0.771 (45.770%)
V2: 12 hours	0.057 (123.900%)	0.451 (197.500%)	0.455 (41.040%)
V3: 1 hour	2.895 (26.430%)	1.607 (133.800%)	1.481 (136.600%)
V3: 2 hours	1.059 (71.460%)	2.349 (81.450%)	2.546 (36.230%)
V3: 3 hours	0.738 (123.900%)	2.376 (102.800%)	2.321 (40.360%)
V3: 4 hours	0.502 (158.300%)	1.921 (125.900%)	1.836 (44.910%)
V3: 6 hours	0.250 (210.700%)	1.400 (162.300%)	1.130 (59.780%)
V3: 8 hours	0.163 (287.500%)	0.889 (218.100%)	0.670 (70.100%)
V3: 12 hours	NA (NA%)^[1]	0.629 (254.300%)	0.356 (99.260%)

No statistical analysis provided for Plasma Concentration of Olaparib

11. Secondary Outcome Measure: Maximum Observed Concentration (Cmax) of Olaparib [ Time Frame: Predose, 1, 2, 3, 4, 6, 8, and 12 hours post dose on V2 (Study Day 1) and V3 (Study Day 8) ]

Measure Type	Secondary
Measure Name	Maximum Observed Concentration (Cmax) of Olaparib
Measure Description	The Cmax of olaparib at V2 (Study Day 1) and V3 (Study Day 8) is reported.
Time Frame	Predose, 1, 2, 3, 4, 6, 8, and 12 hours post dose on V2 (Study Day 1) and V3 (Study Day 8)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK analysis set included subset of safety analysis set including participants who had reportable PK data for olaparib both alone at V2 and in combination with cisplatin at V3.

Reporting Groups

	Description
Cohort 1: Continuous Dosing	Participants received oral olaparib capsule 50 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 50 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 50 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 2: Continuous Dosing	Participants received oral olaparib capsule 100 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 100 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 100 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 3: Continuous Dosing	Participants received oral olaparib capsule 200 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 200 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 200 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.

Measured Values

	Cohort 1: Continuous Dosing	Cohort 2: Continuous Dosing	Cohort 3: Continuous Dosing
Number of Participants Analyzed [units:participants]	3	12	6
Maximum Observed Concentration (Cmax) of Olaparib [units: μg/mL] Geometric Mean (Geometric Coefficient of Variation)
V2	1.581 (117.900%)	3.272 (56.600%)	3.557 (13.620%)
V3	2.895 (26.430%)	3.185 (68.180%)	3.020 (37.560%)

No statistical analysis provided for Maximum Observed Concentration (Cmax) of Olaparib

12. Secondary Outcome Measure: Time to Reach Maximum Observed Serum Concentration (Tmax) of Olaparib [ Time Frame: Predose, 1, 2, 3, 4, 6, 8, and 12 hours post dose on V2 (Study Day 1) and V3 (Study Day 8) ]

Measure Type	Secondary
Measure Name	Time to Reach Maximum Observed Serum Concentration (Tmax) of Olaparib
Measure Description	The Tmax of olaparib at V2 (Study Day 1) and V3 (Study Day 8) is reported.
Time Frame	Predose, 1, 2, 3, 4, 6, 8, and 12 hours post dose on V2 (Study Day 1) and V3 (Study Day 8)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK analysis set included subset of safety analysis set including participants who had reportable PK data for olaparib both alone at V2 and in combination with cisplatin at V3.

Reporting Groups

	Description
Cohort 1: Continuous Dosing	Participants received oral olaparib capsule 50 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 50 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 50 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 2: Continuous Dosing	Participants received oral olaparib capsule 100 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 100 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 100 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 3: Continuous Dosing	Participants received oral olaparib capsule 200 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 200 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 200 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.

Measured Values

	Cohort 1: Continuous Dosing	Cohort 2: Continuous Dosing	Cohort 3: Continuous Dosing
Number of Participants Analyzed [units:participants]	3	12	6
Time to Reach Maximum Observed Serum Concentration (Tmax) of Olaparib [units: Hour] Median (Full Range)
V2	1.000 (1.000 to 2.000)	2.000 (1.000 to 4.000)	2.000 (1.000 to 3.000)
V3	1.000 (1.000 to 1.000)	2.000 (1.000 to 6.000)	1.500 (1.000 to 3.000)

No statistical analysis provided for Time to Reach Maximum Observed Serum Concentration (Tmax) of Olaparib

13. Secondary Outcome Measure: Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Olaparib [ Time Frame: Predose, 1, 2, 3, 4, 6, 8, and 12 hours post dose on V2 (Study Day 1) and V3 (Study Day 8) ]

Measure Type	Secondary
Measure Name	Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Olaparib
Measure Description	The AUC0-t of olaparib at V2 (Study Day 1) and V3 (Study Day 8) is reported.
Time Frame	Predose, 1, 2, 3, 4, 6, 8, and 12 hours post dose on V2 (Study Day 1) and V3 (Study Day 8)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK analysis set included subset of safety analysis set including participants who had reportable PK data for olaparib both alone at V2 and in combination with cisplatin at V3.

Reporting Groups

	Description
Cohort 1: Continuous Dosing	Participants received oral olaparib capsule 50 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 50 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 50 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 2: Continuous Dosing	Participants received oral olaparib capsule 100 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 100 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 100 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 3: Continuous Dosing	Participants received oral olaparib capsule 200 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 200 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 200 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.

Measured Values

	Cohort 1: Continuous Dosing	Cohort 2: Continuous Dosing	Cohort 3: Continuous Dosing
Number of Participants Analyzed [units:participants]	3	12	6
Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Olaparib [units: μg.h/mL] Geometric Mean (Geometric Coefficient of Variation)
V2	4.433 (109.800%)	15.310 (103.500%)	16.520 (25.470%)
V3	7.401 (40.560%)	16.210 (113.600%)	14.380 (35.230%)

No statistical analysis provided for Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Olaparib

Serious Adverse Events

Time Frame	Day 1 through Day 1181 (maximum observed duration)
Additional Description	Safety analysis set included all participants who received at least one dose of olaparib.

Reporting Groups

	Description
Cohort 1: Continuous Dosing	Participants received oral olaparib capsule 50 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 50 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 50 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 2: Continuous Dosing	Participants received oral olaparib capsule 100 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 100 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 100 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 3: Continuous Dosing	Participants received oral olaparib capsule 200 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 200 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 200 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 4: Intermittent Dosing	Participants received oral olaparib capsule 100 mg BID on Days 1 to 10 and IV cisplatin infusion 75 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 5: Intermittent Dosing	Participants received oral olaparib capsule 50 mg BID on Days 1 to 10 and IV cisplatin infusion 75 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 6: Intermittent Dosing	Participants received oral olaparib capsule 50 mg BID on Days 1 to 10 and IV cisplatin infusion 60 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.

Serious Adverse Events

Cohort 1: Continuous Dosing

Cohort 2: Continuous Dosing

Cohort 3: Continuous Dosing

Cohort 4: Intermittent Dosing

Cohort 5: Intermittent Dosing

Cohort 6: Intermittent Dosing

Total, serious adverse events

# participants affected / at risk

0/3 (0.00%)

3/13 (23.08%)

2/6 (33.33%)

2/14 (14.29%)

4/6 (66.67%)

5/12 (41.67%)

Metabolism and nutrition disorders

Diabetes mellitus inadequate control¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

# events

Metabolism and nutrition disorders

Electrolyte imbalance¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Nervous system disorders

Migraine¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

1/6 (16.67%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Nervous system disorders

Neuralgia¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Psychiatric disorders

Depression¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Renal and urinary disorders

Renal failure acute¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

# events

Renal and urinary disorders

Renal vein thrombosis¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

1/6 (16.67%)

0/14 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pulmonary embolism¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

0/14 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

# events

Vascular disorders

Deep vein thrombosis¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

1/6 (16.67%)

1/12 (8.33%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

1/12 (8.33%)

# events

Gastrointestinal disorders

Small intestinal obstruction¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

1/12 (8.33%)

# events

General disorders and administration site conditions

Pyrexia¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Infections and infestations

Bronchitis¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

# events

Infections and infestations

Cellulitis¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

# events

Infections and infestations

Device related infection¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Infections and infestations

Upper respiratory tract infection¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

# events

Blood and lymphatic system disorders

Thrombocytopenia¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Injury, poisoning and procedural complications

Toxicity to various agents¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 14.1

Other Adverse Events

Time Frame	Day 1 through Day 1181 (maximum observed duration)
Additional Description	Safety analysis set included all participants who received at least one dose of olaparib.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Cohort 1: Continuous Dosing	Participants received oral olaparib capsule 50 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 50 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 50 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 2: Continuous Dosing	Participants received oral olaparib capsule 100 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 100 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 100 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 3: Continuous Dosing	Participants received oral olaparib capsule 200 mg once on Study Day 1 and thereafter received combination therapy of oral olaparib capsule 200 mg twice daily (BID) and intravenous (IV) cisplatin infusion 75 mg/m^2 on Day 1 (Study Day 8) of 21-day cycle. Participants continued receiving oral olaparib 200 mg BID until Day 21 of the cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 4: Intermittent Dosing	Participants received oral olaparib capsule 100 mg BID on Days 1 to 10 and IV cisplatin infusion 75 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 5: Intermittent Dosing	Participants received oral olaparib capsule 50 mg BID on Days 1 to 10 and IV cisplatin infusion 75 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.
Cohort 6: Intermittent Dosing	Participants received oral olaparib capsule 50 mg BID on Days 1 to 10 and IV cisplatin infusion 60 mg/m^2 on Day 1 of 21-day cycle. Participants continued receiving combination therapy until Cycle 6 or until they received benefit and were free from significant toxicity. Post cisplatin discontinuation after Cycle 6, participants continued receiving oral olaparib capsule 400 mg BID (monotherapy phase) at the investigator’s discretion until participants received benefit or not met disease progression or any other discontinuation criteria.

Other Adverse Events

Cohort 1: Continuous Dosing

Cohort 2: Continuous Dosing

Cohort 3: Continuous Dosing

Cohort 4: Intermittent Dosing

Cohort 5: Intermittent Dosing

Cohort 6: Intermittent Dosing

Total, other (not including serious) adverse events

# participants affected / at risk

3/3 (100.00%)

13/13 (100.00%)

6/6 (100.00%)

14/14 (100.00%)

6/6 (100.00%)

12/12 (100.00%)

Blood and lymphatic system disorders

Thrombocytosis¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Investigations

Aspartate aminotransferase increased¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Investigations

Bacterial test¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Investigations

Bacterial test positive¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Investigations

Blood alkaline phosphatase increased¹,^†

# participants affected / at risk

2/3 (66.67%)

2/13 (15.38%)

1/6 (16.67%)

1/14 (7.14%)

0/6 (0.00%)

1/12 (8.33%)

# events

Investigations

Blood amylase increased¹,^†

# participants affected / at risk

1/3 (33.33%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Investigations

Blood chloride decreased¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Investigations

Blood creatinine increased¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

0/14 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

# events

Investigations

Blood glucose increased¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

2/14 (14.29%)

0/6 (0.00%)

0/12 (0.00%)

# events

Investigations

Blood lactate dehydrogenase increased¹,^†

# participants affected / at risk

0/3 (0.00%)

3/13 (23.08%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Investigations

Blood phosphorus decreased¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Cardiac disorders

Palpitations¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

1/6 (16.67%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Investigations

Blood potassium decreased¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Investigations

Blood urea increased¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

1/12 (8.33%)

# events

Investigations

Blood urine present¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Investigations

Gamma-glutamyltransferase increased¹,^†

# participants affected / at risk

0/3 (0.00%)

3/13 (23.08%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Investigations

Globulin¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Investigations

Globulins decreased¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Investigations

Glucose urine¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Investigations

Glucose urine present¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Investigations

International normalised ratio increased¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Investigations

Lipase¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Cardiac disorders

Sinus tachycardia¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Investigations

Lipase increased¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

1/6 (16.67%)

2/14 (14.29%)

0/6 (0.00%)

0/12 (0.00%)

# events

Investigations

Low density lipoprotein increased¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Investigations

Neutrophil count decreased¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Investigations

Neutrophil count increased¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Investigations

Protein total decreased¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Investigations

Protein urine present¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

2/14 (14.29%)

0/6 (0.00%)

0/12 (0.00%)

# events

Investigations

Prothrombin time prolonged¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Investigations

Red blood cells urine¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Investigations

Red blood cells urine positive¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Investigations

Urinary sediment present¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Cardiac disorders

Tachycardia¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

1/6 (16.67%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Investigations

Weight decreased¹,^†

# participants affected / at risk

0/3 (0.00%)

2/13 (15.38%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Investigations

White blood cell count decreased¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Investigations

White blood cell count increased¹,^†

# participants affected / at risk

0/3 (0.00%)

2/13 (15.38%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

1/12 (8.33%)

# events

Investigations

White blood cells urine positive¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

2/14 (14.29%)

0/6 (0.00%)

0/12 (0.00%)

# events

Metabolism and nutrition disorders

Acidosis¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Metabolism and nutrition disorders

Decreased appetite¹,^†

# participants affected / at risk

0/3 (0.00%)

7/13 (53.85%)

2/6 (33.33%)

2/14 (14.29%)

2/6 (33.33%)

3/12 (25.00%)

# events

Metabolism and nutrition disorders

Dehydration¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

2/6 (33.33%)

2/14 (14.29%)

0/6 (0.00%)

3/12 (25.00%)

# events

Metabolism and nutrition disorders

Diabetes mellitus¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Ear and labyrinth disorders

Deafness¹,^†

# participants affected / at risk

3/3 (100.00%)

1/13 (7.69%)

2/6 (33.33%)

2/14 (14.29%)

0/6 (0.00%)

1/12 (8.33%)

# events

Metabolism and nutrition disorders

Gout¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Metabolism and nutrition disorders

Hypercholesterolaemia¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Metabolism and nutrition disorders

Hyperglycaemia¹,^†

# participants affected / at risk

0/3 (0.00%)

3/13 (23.08%)

1/6 (16.67%)

1/14 (7.14%)

0/6 (0.00%)

1/12 (8.33%)

# events

Metabolism and nutrition disorders

Hyperkalaemia¹,^†

# participants affected / at risk

1/3 (33.33%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Metabolism and nutrition disorders

Hyperphosphataemia¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Metabolism and nutrition disorders

Hypertriglyceridaemia¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Metabolism and nutrition disorders

Hypoalbuminaemia¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Metabolism and nutrition disorders

Hypocalcaemia¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Metabolism and nutrition disorders

Hypochloraemia¹,^†

# participants affected / at risk

1/3 (33.33%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Metabolism and nutrition disorders

Hypokalaemia¹,^†

# participants affected / at risk

1/3 (33.33%)

0/13 (0.00%)

1/6 (16.67%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Ear and labyrinth disorders

Deafness unilateral¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Metabolism and nutrition disorders

Hypomagnesaemia¹,^†

# participants affected / at risk

1/3 (33.33%)

3/13 (23.08%)

2/6 (33.33%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Metabolism and nutrition disorders

Hyponatraemia¹,^†

# participants affected / at risk

1/3 (33.33%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

1/12 (8.33%)

# events

Metabolism and nutrition disorders

Hypophosphataemia¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

1/6 (16.67%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

1/3 (33.33%)

0/13 (0.00%)

1/6 (16.67%)

3/14 (21.43%)

0/6 (0.00%)

2/12 (16.67%)

# events

Musculoskeletal and connective tissue disorders

Back pain¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

1/6 (16.67%)

3/14 (21.43%)

1/6 (16.67%)

1/12 (8.33%)

# events

Musculoskeletal and connective tissue disorders

Bone pain¹,^†

# participants affected / at risk

0/3 (0.00%)

2/13 (15.38%)

1/6 (16.67%)

1/14 (7.14%)

1/6 (16.67%)

0/12 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Groin pain¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Musculoskeletal and connective tissue disorders

Muscle contracture¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

1/6 (16.67%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Muscular weakness¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

1/6 (16.67%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal chest pain¹,^†

# participants affected / at risk

0/3 (0.00%)

4/13 (30.77%)

2/6 (33.33%)

3/14 (21.43%)

1/6 (16.67%)

0/12 (0.00%)

# events

Ear and labyrinth disorders

Ear pain¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

1/6 (16.67%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal pain¹,^†

# participants affected / at risk

1/3 (33.33%)

0/13 (0.00%)

2/6 (33.33%)

2/14 (14.29%)

2/6 (33.33%)

1/12 (8.33%)

# events

Musculoskeletal and connective tissue disorders

Myalgia¹,^†

# participants affected / at risk

2/3 (66.67%)

0/13 (0.00%)

2/6 (33.33%)

0/14 (0.00%)

2/6 (33.33%)

0/12 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Neck pain¹,^†

# participants affected / at risk

1/3 (33.33%)

0/13 (0.00%)

0/6 (0.00%)

2/14 (14.29%)

1/6 (16.67%)

1/12 (8.33%)

# events

Musculoskeletal and connective tissue disorders

Pain in extremity¹,^†

# participants affected / at risk

1/3 (33.33%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Pain in jaw¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Musculoskeletal and connective tissue disorders

Tendon pain¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Malignant muscle neoplasm¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Tumour associated fever¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

0/14 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

# events

Nervous system disorders

Amnesia¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

1/6 (16.67%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Nervous system disorders

Aphasia¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

1/6 (16.67%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Ear and labyrinth disorders

Hearing impaired¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Nervous system disorders

Burning sensation¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

1/6 (16.67%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Nervous system disorders

Coordination abnormal¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Nervous system disorders

Disturbance in attention¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

0/3 (0.00%)

4/13 (30.77%)

2/6 (33.33%)

0/14 (0.00%)

1/6 (16.67%)

2/12 (16.67%)

# events

Nervous system disorders

Dysgeusia¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

1/6 (16.67%)

5/14 (35.71%)

3/6 (50.00%)

3/12 (25.00%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

1/3 (33.33%)

1/13 (7.69%)

3/6 (50.00%)

4/14 (28.57%)

3/6 (50.00%)

4/12 (33.33%)

# events

Nervous system disorders

Hyperaesthesia¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Nervous system disorders

Hypoaesthesia¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

# events

Nervous system disorders

Hypokinesia¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

# events

Ear and labyrinth disorders

Ototoxicity¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

2/6 (33.33%)

1/12 (8.33%)

# events

Nervous system disorders

Neuropathy peripheral¹,^†

# participants affected / at risk

2/3 (66.67%)

1/13 (7.69%)

0/6 (0.00%)

1/14 (7.14%)

1/6 (16.67%)

3/12 (25.00%)

# events

Nervous system disorders

Neurotoxicity¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

3/14 (21.43%)

0/6 (0.00%)

0/12 (0.00%)

# events

Nervous system disorders

Paraesthesia¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

1/6 (16.67%)

3/14 (21.43%)

0/6 (0.00%)

1/12 (8.33%)

# events

Nervous system disorders

Peripheral sensory neuropathy¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

1/6 (16.67%)

3/14 (21.43%)

0/6 (0.00%)

1/12 (8.33%)

# events

Nervous system disorders

Post-traumatic headache¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

# events

Nervous system disorders

Sinus headache¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Nervous system disorders

Somnolence¹,^†

# participants affected / at risk

0/3 (0.00%)

4/13 (30.77%)

0/6 (0.00%)

0/14 (0.00%)

3/6 (50.00%)

0/12 (0.00%)

# events

Nervous system disorders

Tension headache¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

1/6 (16.67%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Psychiatric disorders

Anxiety¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

1/6 (16.67%)

2/14 (14.29%)

1/6 (16.67%)

0/12 (0.00%)

# events

Ear and labyrinth disorders

Tinnitus¹,^†

# participants affected / at risk

1/3 (33.33%)

4/13 (30.77%)

4/6 (66.67%)

7/14 (50.00%)

3/6 (50.00%)

4/12 (33.33%)

# events

Psychiatric disorders

Depressed mood¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Psychiatric disorders

Depression¹,^†

# participants affected / at risk

1/3 (33.33%)

0/13 (0.00%)

0/6 (0.00%)

3/14 (21.43%)

1/6 (16.67%)

0/12 (0.00%)

# events

Psychiatric disorders

Insomnia¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

2/6 (33.33%)

5/14 (35.71%)

2/6 (33.33%)

2/12 (16.67%)

# events

Psychiatric disorders

Nervousness¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

2/6 (33.33%)

0/12 (0.00%)

# events

Psychiatric disorders

Nightmare¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Psychiatric disorders

Sleep disorder¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

1/6 (16.67%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Renal and urinary disorders

Bladder pain¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Renal and urinary disorders

Dysuria¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

3/14 (21.43%)

0/6 (0.00%)

0/12 (0.00%)

# events

Renal and urinary disorders

Ketonuria¹,^†

# participants affected / at risk

1/3 (33.33%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Renal and urinary disorders

Nephropathy toxic¹,^†

# participants affected / at risk

1/3 (33.33%)

0/13 (0.00%)

1/6 (16.67%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

1/3 (33.33%)

6/13 (46.15%)

4/6 (66.67%)

3/14 (21.43%)

3/6 (50.00%)

3/12 (25.00%)

# events

Endocrine disorders

Cushingoid¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Renal and urinary disorders

Nocturia¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Renal and urinary disorders

Pollakiuria¹,^†

# participants affected / at risk

1/3 (33.33%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Renal and urinary disorders

Proteinuria¹,^†

# participants affected / at risk

1/3 (33.33%)

1/13 (7.69%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Renal and urinary disorders

Urinary incontinence¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Renal and urinary disorders

Urinary retention¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Renal and urinary disorders

Urinary tract pain¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Reproductive system and breast disorders

Breast discomfort¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

# events

Reproductive system and breast disorders

Breast pain¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

2/14 (14.29%)

0/6 (0.00%)

1/12 (8.33%)

# events

Eye disorders

Conjunctival haemorrhage¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Respiratory, thoracic and mediastinal disorders

Bronchial hyperreactivity¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Bronchial secretion retention¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

0/3 (0.00%)

3/13 (23.08%)

0/6 (0.00%)

4/14 (28.57%)

1/6 (16.67%)

4/12 (33.33%)

# events

Respiratory, thoracic and mediastinal disorders

Dysphonia¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

1/3 (33.33%)

2/13 (15.38%)

0/6 (0.00%)

2/14 (14.29%)

1/6 (16.67%)

1/12 (8.33%)

# events

Respiratory, thoracic and mediastinal disorders

Epistaxis¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

2/14 (14.29%)

0/6 (0.00%)

0/12 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Hypoxia¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

1/6 (16.67%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Nasal congestion¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

2/14 (14.29%)

0/6 (0.00%)

4/12 (33.33%)

# events

Respiratory, thoracic and mediastinal disorders

Oropharyngeal pain¹,^†

# participants affected / at risk

0/3 (0.00%)

2/13 (15.38%)

1/6 (16.67%)

1/14 (7.14%)

0/6 (0.00%)

1/12 (8.33%)

# events

Respiratory, thoracic and mediastinal disorders

Orthopnoea¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

1/6 (16.67%)

0/14 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

# events

Eye disorders

Dry eye¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pharyngeal inflammation¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pleuritic pain¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Respiratory, thoracic and mediastinal disorders

Pneumothorax¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Respiratory, thoracic and mediastinal disorders

Productive cough¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pulmonary embolism¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Rhinitis allergic¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Rhinorrhoea¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Respiratory, thoracic and mediastinal disorders

Wheezing¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Skin and subcutaneous tissue disorders

Alopecia¹,^†

# participants affected / at risk

1/3 (33.33%)

0/13 (0.00%)

0/6 (0.00%)

2/14 (14.29%)

0/6 (0.00%)

3/12 (25.00%)

# events

Skin and subcutaneous tissue disorders

Cold sweat¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Eye disorders

Eye pain¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Skin and subcutaneous tissue disorders

Dermatitis acneiform¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Skin and subcutaneous tissue disorders

Dry skin¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

1/6 (16.67%)

0/12 (0.00%)

# events

Skin and subcutaneous tissue disorders

Ecchymosis¹,^†

# participants affected / at risk

1/3 (33.33%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Skin and subcutaneous tissue disorders

Erythema¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

1/6 (16.67%)

0/12 (0.00%)

# events

Skin and subcutaneous tissue disorders

Erythema nodosum¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

1/6 (16.67%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Skin and subcutaneous tissue disorders

Hyperhidrosis¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Skin and subcutaneous tissue disorders

Onychoclasis¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Skin and subcutaneous tissue disorders

Palmar-plantar erythrodysaesthesia syndrome¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Skin and subcutaneous tissue disorders

Photosensitivity reaction¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Skin and subcutaneous tissue disorders

Pruritus¹,^†

# participants affected / at risk

1/3 (33.33%)

0/13 (0.00%)

0/6 (0.00%)

2/14 (14.29%)

2/6 (33.33%)

2/12 (16.67%)

# events

Eye disorders

Macular degeneration¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

1/6 (16.67%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Skin and subcutaneous tissue disorders

Rash¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

3/14 (21.43%)

1/6 (16.67%)

0/12 (0.00%)

# events

Skin and subcutaneous tissue disorders

Rash papular¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Skin and subcutaneous tissue disorders

Swelling face¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Vascular disorders

Flushing¹,^†

# participants affected / at risk

1/3 (33.33%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Vascular disorders

Hot flush¹,^†

# participants affected / at risk

1/3 (33.33%)

0/13 (0.00%)

1/6 (16.67%)

0/14 (0.00%)

2/6 (33.33%)

0/12 (0.00%)

# events

Vascular disorders

Hypertension¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

1/6 (16.67%)

0/12 (0.00%)

# events

Vascular disorders

Lymphoedema¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

2/6 (33.33%)

1/14 (7.14%)

1/6 (16.67%)

0/12 (0.00%)

# events

Eye disorders

Miosis¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Eye disorders

Scotoma¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

# events

Eye disorders

Vision blurred¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

2/14 (14.29%)

0/6 (0.00%)

0/12 (0.00%)

# events

Eye disorders

Visual acuity reduced¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

1/6 (16.67%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Gastrointestinal disorders

Abdominal discomfort¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

2/6 (33.33%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Blood and lymphatic system disorders

Hypoglobulinaemia¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Gastrointestinal disorders

Abdominal distension¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Gastrointestinal disorders

Abdominal pain¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

2/14 (14.29%)

2/6 (33.33%)

2/12 (16.67%)

# events

Gastrointestinal disorders

Abdominal pain upper¹,^†

# participants affected / at risk

1/3 (33.33%)

2/13 (15.38%)

2/6 (33.33%)

2/14 (14.29%)

0/6 (0.00%)

1/12 (8.33%)

# events

Gastrointestinal disorders

Aerophagia¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Gastrointestinal disorders

Anal pruritus¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

# events

Gastrointestinal disorders

Ascites¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

2/14 (14.29%)

0/6 (0.00%)

0/12 (0.00%)

# events

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

1/3 (33.33%)

7/13 (53.85%)

3/6 (50.00%)

5/14 (35.71%)

1/6 (16.67%)

7/12 (58.33%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

0/3 (0.00%)

4/13 (30.77%)

1/6 (16.67%)

4/14 (28.57%)

2/6 (33.33%)

6/12 (50.00%)

# events

Gastrointestinal disorders

Dyspepsia¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

1/6 (16.67%)

3/14 (21.43%)

2/6 (33.33%)

1/12 (8.33%)

# events

Gastrointestinal disorders

Dysphagia¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Blood and lymphatic system disorders

Leukocytosis¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Gastrointestinal disorders

Flatulence¹,^†

# participants affected / at risk

1/3 (33.33%)

1/13 (7.69%)

1/6 (16.67%)

1/14 (7.14%)

1/6 (16.67%)

0/12 (0.00%)

# events

Gastrointestinal disorders

Gastric ulcer¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Gastrointestinal disorders

Gastritis¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

2/6 (33.33%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Gastrointestinal disorders

Gastrooesophageal reflux disease¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

# events

Gastrointestinal disorders

Gingival pain¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Gastrointestinal disorders

Glossodynia¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Gastrointestinal disorders

Haemorrhoids¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

2/3 (66.67%)

9/13 (69.23%)

4/6 (66.67%)

12/14 (85.71%)

4/6 (66.67%)

10/12 (83.33%)

# events

Gastrointestinal disorders

Oral pain¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Gastrointestinal disorders

Pancreatitis¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Blood and lymphatic system disorders

Leukopenia¹,^†

# participants affected / at risk

1/3 (33.33%)

6/13 (46.15%)

0/6 (0.00%)

5/14 (35.71%)

0/6 (0.00%)

0/12 (0.00%)

# events

Gastrointestinal disorders

Stomatitis¹,^†

# participants affected / at risk

0/3 (0.00%)

3/13 (23.08%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

2/12 (16.67%)

# events

Gastrointestinal disorders

Toothache¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

2/3 (66.67%)

8/13 (61.54%)

2/6 (33.33%)

7/14 (50.00%)

4/6 (66.67%)

4/12 (33.33%)

# events

General disorders and administration site conditions

Asthenia¹,^†

# participants affected / at risk

1/3 (33.33%)

6/13 (46.15%)

3/6 (50.00%)

6/14 (42.86%)

4/6 (66.67%)

2/12 (16.67%)

# events

General disorders and administration site conditions

Atrophy¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

General disorders and administration site conditions

Axillary pain¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

General disorders and administration site conditions

Catheter site pain¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

# events

General disorders and administration site conditions

Chest pain¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

# events

General disorders and administration site conditions

Fatigue¹,^†

# participants affected / at risk

2/3 (66.67%)

6/13 (46.15%)

3/6 (50.00%)

5/14 (35.71%)

1/6 (16.67%)

7/12 (58.33%)

# events

Blood and lymphatic system disorders

Lymphopenia¹,^†

# participants affected / at risk

1/3 (33.33%)

1/13 (7.69%)

0/6 (0.00%)

3/14 (21.43%)

0/6 (0.00%)

1/12 (8.33%)

# events

General disorders and administration site conditions

Feeling jittery¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

1/6 (16.67%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

General disorders and administration site conditions

Influenza like illness¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

General disorders and administration site conditions

Localised oedema¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

General disorders and administration site conditions

Malaise¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

2/6 (33.33%)

0/12 (0.00%)

# events

General disorders and administration site conditions

Mucosal inflammation¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

1/6 (16.67%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

General disorders and administration site conditions

Non-cardiac chest pain¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

# events

General disorders and administration site conditions

Oedema peripheral¹,^†

# participants affected / at risk

1/3 (33.33%)

1/13 (7.69%)

1/6 (16.67%)

2/14 (14.29%)

0/6 (0.00%)

1/12 (8.33%)

# events

General disorders and administration site conditions

Pyrexia¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

3/14 (21.43%)

0/6 (0.00%)

0/12 (0.00%)

# events

General disorders and administration site conditions

Thrombosis in device¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

1/6 (16.67%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Hepatobiliary disorders

Hepatomegaly¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

1/12 (8.33%)

# events

Blood and lymphatic system disorders

Macrocytosis¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

1/6 (16.67%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Immune system disorders

Seasonal allergy¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

1/6 (16.67%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Infections and infestations

Bacterial infection¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Infections and infestations

Bronchitis¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

# events

Infections and infestations

Candidiasis¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Infections and infestations

Cystitis¹,^†

# participants affected / at risk

1/3 (33.33%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Infections and infestations

Gastroenteritis¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

# events

Infections and infestations

Gastroenteritis viral¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Infections and infestations

Herpes zoster¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

1/6 (16.67%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Blood and lymphatic system disorders

Neutropenia¹,^†

# participants affected / at risk

3/3 (100.00%)

5/13 (38.46%)

4/6 (66.67%)

6/14 (42.86%)

1/6 (16.67%)

3/12 (25.00%)

# events

Infections and infestations

Infected bites¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

2/6 (33.33%)

1/14 (7.14%)

2/6 (33.33%)

1/12 (8.33%)

# events

Infections and infestations

Onychomycosis¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Infections and infestations

Respiratory tract infection¹,^†

# participants affected / at risk

1/3 (33.33%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

# events

Infections and infestations

Rhinitis¹,^†

# participants affected / at risk

1/3 (33.33%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Infections and infestations

Sinusitis¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Infections and infestations

Upper respiratory tract infection¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

1/12 (8.33%)

# events

Infections and infestations

Urinary tract infection¹,^†

# participants affected / at risk

1/3 (33.33%)

5/13 (38.46%)

0/6 (0.00%)

2/14 (14.29%)

1/6 (16.67%)

2/12 (16.67%)

# events

Injury, poisoning and procedural complications

Arthropod bite¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Blood and lymphatic system disorders

Thrombocytopenia¹,^†

# participants affected / at risk

2/3 (66.67%)

3/13 (23.08%)

3/6 (50.00%)

2/14 (14.29%)

0/6 (0.00%)

0/12 (0.00%)

# events

Injury, poisoning and procedural complications

Foot fracture¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Injury, poisoning and procedural complications

Humerus fracture¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Injury, poisoning and procedural complications

Sunburn¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

1/6 (16.67%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Injury, poisoning and procedural complications

Thermal burn¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Injury, poisoning and procedural complications

Tooth injury¹,^†

# participants affected / at risk

0/3 (0.00%)

0/13 (0.00%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

# events

Injury, poisoning and procedural complications

Urinary anastomotic leak¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Investigations

Activated partial thromboplastin time prolonged¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

0/14 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

# events

Investigations

Activated partial thromboplastin time shortened¹,^†

# participants affected / at risk

0/3 (0.00%)

1/13 (7.69%)

0/6 (0.00%)

1/14 (7.14%)

0/6 (0.00%)

0/12 (0.00%)

# events

Investigations

Alanine aminotransferase increased¹,^†

# participants affected / at risk

1/3 (33.33%)

3/13 (23.08%)

0/6 (0.00%)

1/14 (7.14%)

1/6 (16.67%)

3/12 (25.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 14.1

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: AstraZeneca has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Global Clinical Lead
Organization:	AstraZeneca Clinical Study Information Center
Phone	+1-877-240-9479
E-mail:	[email protected]

Documents available

Download
Cancer Study Locator (US and Canada only)
Download
D0810C00021 redacted protocol
Download
CSR Synopsis redacted
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Contact Backup

AstraZeneca Cancer Study Locator Service

877-400-4656

astrazeneca@emergingmed.com

Investigators

Principal Investigator

Jane Robertson

AstraZeneca

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Cancer Study Locator (US and Canada only)

D0810C00021 redacted protocol

CSR Synopsis redacted

Trial Results Summaries