A pharmacokinetic (PK) and pharmacodynamic (PD) dose-ranging Phase II study of ticagrelor in paediatric patients with sickle cell disease - HESTIA 1

Study identifier:D5136C00007

ClinicalTrials.gov identifier:NCT02214121

EudraCT identifier:2014-001006-18

CTIS identifier:N/A

Study Complete

Official Title

Multicenter, open-label, randomised, pharmacokinetic (PK) and pharmacodynamic (PD) dose-ranging Phase II study of ticagrelor followed by a double-blind, randomised, parallel-group, placebo-controlled 4 weeks extension phase in paediatric patients with sickle cell disease

Medical condition

Investigation of platelet aggregation in paediatric patients with sickle cell Disease

Phase

Phase 2

Healthy volunteers

Study drug

Ticagrelor Dose 1a + Dose 2a, Ticagrelor Dose 1b + Dose 2b

Sex

All

Actual Enrollment

Study type

Interventional

Age

2 Years - 17 Years

Date

Study Start Date: 11 Sept 2014

Primary Completion Date: 27 Feb 2017

Study Completion Date: 27 Feb 2017

Study design

Allocation: Randomized
Endpoint Classification: Pharmacokinetics/dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Nov 2018 by AstraZeneca

Collaborators

None

Inclusion and exclusion criteria

Location

Research Site

Toronto, ON, Canada, M5G 1X8

Location

Research Site

CARDIFF, United Kingdom, CF4 4XN

Location

Research Site

Parow, South Africa, 7500

Location

Research Site

London, United Kingdom, SE1 7EH

Location

Research Site

LONDON, United Kingdom, E1 1BB

Location

Research Site

Hershey, PA, United States, 17022

Location

Research Site

Charleston, SC, United States, 29425

Location

Research Site

Orange, CA, United States, 92868

Arms	Assigned Interventions
Other: Ticagrelor Dose 1a + Dose 2a Part A: Ticagrelor Dose 1a and ticagrelor Dose 2a single doses + 1 week repeated dosing Part B: Ticagrelor or placebo 4 weeks repeated dosing.	Drug: Ticagrelor Dose 1a + Dose 2a Ticagrelor Dose 1a and ticagrelor Dose 2a single doses + 1 week ticagrelor repeated dosing followed by 4 weeks repeated dosing ticagrelor or placebo.
Other: Ticagrelor Dose 1b + Dose 2b Part A: Ticagrelor Dose 1b and ticagrelor Dose 2b single doses + 1 week repeated dosing. Part B: Ticagrelor or placebo 4 weeks repeated dosing.	Drug: Ticagrelor Dose 1b + Dose 2b Ticagrelor Dose 1b and ticagrelor Dose 2b single doses + 1 week ticagrelor repeted dosing followed by 4 weeks repeated dosing ticagrelor or placebo.

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 24 centres, in 6 countries. The first patient was enrolled to Part A of the study on 11 Sep 2014, and the last patient completed Part B of the study on 27 Feb 2017. Recruitment was stopped due to protocol amendment between 8 September 2015 and 1 June 2016.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
46 patients were randomised to Part A of the study (open label). Of the patients completing Part A, 25 were randomised to Part B of the study (double blind)

Reporting Groups

	Description
Part A - Ticagrelor	Randomised treatment group for Part A of the study. Relevant for the Part A period.
Part B - Ticagrelor	Randomised treatment group for Part B of the study. Relevant for the Part B period.
Part B - Placebo	Randomised treatment group for Part B of the study. Relevant for the Part B period.

Participant Flow for 2 periods

Period 1: Part A

	Part A - Ticagrelor	Part B - Ticagrelor	Part B - Placebo
STARTED	46	0	0
COMPLETED	39	0	0
NOT COMPLETED	7	0	0
Patient decision	2	0	0
Dev. of study-specific withdrawal crit.	4	0	0
Other	1	0	0

Period 2: Part B

	Part B - Ticagrelor	Part B - Placebo
STARTED	17	8
COMPLETED	14	7
NOT COMPLETED	3	1
Patient decision	1	0
Dev. of study-specific withdrawal crit.	2	0
Lost to Follow-up	0	1

Baseline Characteristics

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

The baseline characteristics are tabulated by the actual treatment group. This differs from the numbers in the Participant Flow since not all randomised patients received IP and one patient receiving treatment not matching the randomised treatment

Reporting Groups

	Description
Part A - Ticagrelor	Actual treatment group for Part A of the study. Relevant for the Part A period.
Part B - Ticagrelor	Actual treatment group for Part B of the study. Relevant for the Part B period.
Part B - Placebo	Actual treatment group for Part B of the study. Relevant for the Part B period.

Baseline Measures

	Part A - Ticagrelor	Part B - Ticagrelor	Part B - Placebo	Total
Number of Participants [units: Participants]	45	16	7	68
Age Continuous ^[1] [units: Years] Mean ± Standard Deviation	11.2 ± 3.34			11.2 ± 3.34
Sex: Female, Male ^[2] [units: ]
Female	24	0	0	24
Male	21	0	0	21
Race/Ethnicity, Customized ^[3] [units: Participants]
White	10	0	0	10
Black or African American	35	0	0	35
Asian	0	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0	0
American Indian or Alaska Native	0	0	0	0
Other	0	0	0	0
Ethnicity (NIH/OMB) ^[4] [units: ]
Hispanic or Latino	1	0	0	1
Not Hispanic or Latino	44	0	0	44
Unknown or Not Reported	0	0	0	0
Age Continuous ^[5] [units: Years] Mean ± Standard Deviation		10.2 ± 3.73	9.7 ± 3.35	10.0 ± 3.55
Sex: Female, Male ^[6] [units: ]
Female	0	9	2	11
Male	0	7	5	12
Race/Ethnicity, Customized ^[7] [units: Participants]
White	0	1	0	1
Black or African American	0	15	7	22
Asian	0	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0	0
American Indian or Alaska Native	0	0	0	0
Other	0	0	0	0
Ethnicity (NIH/OMB) ^[8] [units: ]
Hispanic or Latino	0	1	0	1
Not Hispanic or Latino	0	15	7	22
Unknown or Not Reported	0	0	0	0

Outcome Measures

1. Primary Outcome Measure: P2Y12 reaction units (PRU) - Part A [ Time Frame: PRU measurements are taken in conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7) and after repeated dosing at Visit 4 (Day 14). Up to 8 hours post-dose (6 hours following protocol amendment) Visit 2 and 3, and up to 2 hours Visit 4. ]

Measure Type	Primary
Measure Name	P2Y12 reaction units (PRU) - Part A
Measure Description
Time Frame	PRU measurements are taken in conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7) and after repeated dosing at Visit 4 (Day 14). Up to 8 hours post-dose (6 hours following protocol amendment) Visit 2 and 3, and up to 2 hours Visit 4.
Safety Issue?	No

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.
The PD analysis set is a subset of the safety analysis set, including all patients having at least one PRU measured. All patients who received at least one single dose of ticagrelor were included in the safety population (SAF) for Part A. Analysis on the SAF was based on the study medication actually received.

Reporting Groups

	Description
Ticagrelor 0.125 mg/kg	Single dose received at Visit 2.
Ticagrelor 0.75 mg/kg	Single dose received at Visit 2.
Ticagrelor 0.375 mg/kg	Single dose received at Visit 3.
Ticagrelor 0.563 mg/kg	Single dose received at Visit 3
Ticagrelor 1.125 mg/kg	Single dose received at Visit 3.
Ticagrelor 2.25 mg/kg	Single dose received at Visit 3.
Ticagrelor 0.125 mg/kg bid	Repeated bid treatment between Visit 3 and Visit 4.
Ticagrelor 0.563 mg/kg bid	Repeated bid treatment between Visit 3 and Visit 4.
Ticagrelor 0.75 mg/kg bid	Repeated bid treatment between Visit 3 and Visit 4.

Measured Values

	Ticagrelor 0.125 mg/kg	Ticagrelor 0.75 mg/kg	Ticagrelor 0.375 mg/kg	Ticagrelor 0.563 mg/kg	Ticagrelor 1.125 mg/kg	Ticagrelor 2.25 mg/kg	Ticagrelor 0.125 mg/kg bid	Ticagrelor 0.563 mg/kg bid	Ticagrelor 0.75 mg/kg bid
Number of Participants Analyzed [units:participants]	14	31	7	18	10	9	14	9	17
P2Y12 reaction units (PRU) - Part A [units: P2Y12 reaction units] Mean (Standard Deviation)
Pre-dose	301.6 (46.55)	268.0 (35.95)	295.4 (42.30)	287.7 (34.35)	283.7 (36.88)	277.7 (39.36)	320 (Not applicable)^[1]	205.4 (53.22)	214.7 (48.71)
2 hours post-dose	278.2 (47.20)	138.4 (70.68)	229.0 (64.22)	176.2 (79.53)	128.9 (37.68)	79.9 (47.74)	271.2 (70.35)	102.0 (72.53)	152.0 (72.35)
6 hours post-dose	276.0 (75.43)	189.0 (69.84)	266.0 (57.98)	190.4 (47.78)	191.2 (57.59)	141.7 (69.58)
8 hours post-dose	343.0 (38.13)		318.3 (66.43)	318.0 (Not applicable)^[1]

No statistical analysis provided for P2Y12 reaction units (PRU) - Part A

2. Primary Outcome Measure: P2Y12 reaction units (PRU) - Part B [ Time Frame: PRU measurements are taken after 4 weeks of double blind treatment at the end of Part B. ]

Measure Type	Primary
Measure Name	P2Y12 reaction units (PRU) - Part B
Measure Description
Time Frame	PRU measurements are taken after 4 weeks of double blind treatment at the end of Part B.
Safety Issue?	No

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.
The PD analysis set is a subset of the safety analysis set, including all patients having at least one PRU measured. All patients who received at least one dose of randomised study drug, ticagrelor or placebo, will be included in the SAF for Part B. Analysis on the SAF was based on the study medication actually received.

Reporting Groups

	Description
Ticagrelor 0.125 mg/kg bid	Repeated bid treatment during Part B.
Placebo	Repeated bid treatment during Part B.

Measured Values

	Ticagrelor 0.125 mg/kg bid	Placebo
Number of Participants Analyzed [units:participants]	9	3
P2Y12 reaction units (PRU) - Part B [units: P2Y12 reaction units] Mean (Standard Deviation)
Pre-dose	282.8 (19.26)	313.3 (20.13)
2 hours post-dose	259.6 (61.95)	217.3 (78.34)

No statistical analysis provided for P2Y12 reaction units (PRU) - Part B

3. Primary Outcome Measure: Maximum plasma concentration (Cmax) - Part A [ Time Frame: PK measurements (up to 8 hours post-dose) are taken in conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7) and after repeated dosing at Visit 4 (Day 14). ]

Measure Type	Primary
Measure Name	Maximum plasma concentration (Cmax) - Part A
Measure Description
Time Frame	PK measurements (up to 8 hours post-dose) are taken in conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7) and after repeated dosing at Visit 4 (Day 14).
Safety Issue?	No

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.
The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one single dose of ticagrelor were included in the safety population (SAF) for Part A. Analysis on the SAF was based on the study medication actually received.

Reporting Groups

	Description
Ticagrelor 0.125 mg/kg	Single dose received at Visit 2.
Ticagrelor 0.75 mg/kg	Single dose received at Visit 2.
Ticagrelor 0.375 mg/kg	Single dose received at Visit 3.
Ticagrelor 0.563 mg/kg	Single dose received at Visit 3
Ticagrelor 1.125 mg/kg	Single dose received at Visit 3.
Ticagrelor 2.25 mg/kg	Single dose received at Visit 3.
Ticagrelor 0.125 mg/kg bid	Repeated bid treatment between Visit 3 and Visit 4.
Ticagrelor 0.563 mg/kg bid	Repeated bid treatment between Visit 3 and Visit 4.
Ticagrelor 0.75 mg/kg bid	Repeated bid treatment between Visit 3 and Visit 4.

Measured Values

	Ticagrelor 0.125 mg/kg	Ticagrelor 0.75 mg/kg	Ticagrelor 0.375 mg/kg	Ticagrelor 0.563 mg/kg	Ticagrelor 1.125 mg/kg	Ticagrelor 2.25 mg/kg	Ticagrelor 0.125 mg/kg bid	Ticagrelor 0.563 mg/kg bid	Ticagrelor 0.75 mg/kg bid
Number of Participants Analyzed [units:participants]	14	31	7	18	10	9	14	9	17
Maximum plasma concentration (Cmax) - Part A [units: ng/mL] Geometric Mean (Standard Deviation)	15.240 (15.2709)	162.961 (84.9230)	52.069 (34.4115)	96.031 (51.4902)	269.174 (162.2147)	566.550 (225.9447)	13.973 (15.3652)	111.367 (81.1597)	157.216 (114.8138)

No statistical analysis provided for Maximum plasma concentration (Cmax) - Part A

4. Primary Outcome Measure: Maximum plasma concentration (Cmax) - Part B [ Time Frame: PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B. ]

Measure Type	Primary
Measure Name	Maximum plasma concentration (Cmax) - Part B
Measure Description
Time Frame	PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B.
Safety Issue?	No

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.
The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one dose of randomised study drug, ticagrelor or placebo, will be included in the SAF for Part B. Analysis on the SAF was based on the study medication actually received.

Reporting Groups

	Description
Ticagrelor 0.125 mg/kg bid	Repeated bid treatment during Part B.

Measured Values

	Ticagrelor 0.125 mg/kg bid
Number of Participants Analyzed [units:participants]	9
Maximum plasma concentration (Cmax) - Part B [units: ng/mL] Geometric Mean (Standard Deviation)	16.394 (13.3671)

No statistical analysis provided for Maximum plasma concentration (Cmax) - Part B

5. Primary Outcome Measure: Area under the plasma concentration time curve (AUC) - Part A [ Time Frame: PK measurements (up to 8 hours post-dose) are taken in conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7) and after repeated dosing at Visit 4 (Day 14). ]

Measure Type	Primary
Measure Name	Area under the plasma concentration time curve (AUC) - Part A
Measure Description	The PK parameter presented was derived using a model based analysis and not from a non-compartmental (NCA) analysis.
Time Frame	PK measurements (up to 8 hours post-dose) are taken in conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7) and after repeated dosing at Visit 4 (Day 14).
Safety Issue?	No

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.
The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one single dose of ticagrelor were included in the safety population (SAF) for Part A. Analysis on the SAF was based on the study medication actually received.

Reporting Groups

	Description
Ticagrelor 0.125 mg/kg	Single dose received at Visit 2.
Ticagrelor 0.75 mg/kg	Single dose received at Visit 2.
Ticagrelor 0.375 mg/kg	Single dose received at Visit 3.
Ticagrelor 0.563 mg/kg	Single dose received at Visit 3
Ticagrelor 1.125 mg/kg	Single dose received at Visit 3.
Ticagrelor 2.25 mg/kg	Single dose received at Visit 3.
Ticagrelor 0.125 mg/kg bid	Repeated bid treatment between Visit 3 and Visit 4.
Ticagrelor 0.563 mg/kg bid	Repeated bid treatment between Visit 3 and Visit 4.
Ticagrelor 0.75 mg/kg bid	Repeated bid treatment between Visit 3 and Visit 4.

Measured Values

	Ticagrelor 0.125 mg/kg	Ticagrelor 0.75 mg/kg	Ticagrelor 0.375 mg/kg	Ticagrelor 0.563 mg/kg	Ticagrelor 1.125 mg/kg	Ticagrelor 2.25 mg/kg	Ticagrelor 0.125 mg/kg bid	Ticagrelor 0.563 mg/kg bid	Ticagrelor 0.75 mg/kg bid
Number of Participants Analyzed [units:participants]	14	31	7	18	10	9	14	9	17
Area under the plasma concentration time curve (AUC) - Part A [units: ng*h/mL] Geometric Mean (Standard Deviation)	161.9 (72.24)	1151.9 (308.39)	437.5 (262.24)	879.3 (236.12)	1638.7 (521.80)	2850.9 (1277.39)	161.9 (72.24)	913.5 (208.82)	1022.4 (287.32)

No statistical analysis provided for Area under the plasma concentration time curve (AUC) - Part A

6. Primary Outcome Measure: Area under the plasma concentration time curve (AUC) - Part B [ Time Frame: PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B. ]

Measure Type	Primary
Measure Name	Area under the plasma concentration time curve (AUC) - Part B
Measure Description	The PK parameter presented was derived using a model based analysis and not from a non-compartmental (NCA) analysis.
Time Frame	PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B.
Safety Issue?	No

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.
The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one dose of randomised study drug, ticagrelor or placebo, will be included in the SAF for Part B. Analysis on the SAF was based on the study medication actually received.

Reporting Groups

	Description
Ticagrelor 0.125 mg/kg bid	Repeated bid treatment during Part B.

Measured Values

	Ticagrelor 0.125 mg/kg bid
Number of Participants Analyzed [units:participants]	9
Area under the plasma concentration time curve (AUC) - Part B [units: ng*h/mL] Geometric Mean (Standard Deviation)	160.6 (88.58)

No statistical analysis provided for Area under the plasma concentration time curve (AUC) - Part B

7. Secondary Outcome Measure: Assessment of Ticagrelor concentration - Part A [ Time Frame: In conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7), after repeated dosing at Visit 4 (Day 14). Up to 8h post-dose (6h following protocol amendment, no pre-dose) Visit 2 and 3, up to 2h Visit 4 (pre-dose, 1h added following amendment) ]

Measure Type	Secondary
Measure Name	Assessment of Ticagrelor concentration - Part A
Measure Description
Time Frame	In conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7), after repeated dosing at Visit 4 (Day 14). Up to 8h post-dose (6h following protocol amendment, no pre-dose) Visit 2 and 3, up to 2h Visit 4 (pre-dose, 1h added following amendment)
Safety Issue?	No

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.
The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one single dose of ticagrelor were included in the safety population (SAF) for Part A. Analysis on the SAF was based on the study medication actually received.

Reporting Groups

	Description
Ticagrelor 0.125 mg/kg	Single dose received at Visit 2.
Ticagrelor 0.75 mg/kg	Single dose received at Visit 2.
Ticagrelor 0.375 mg/kg	Single dose received at Visit 3.
Ticagrelor 0.563 mg/kg	Single dose received at Visit 3
Ticagrelor 1.125 mg/kg	Single dose received at Visit 3.
Ticagrelor 2.25 mg/kg	Single dose received at Visit 3.
Ticagrelor 0.125 mg/kg bid	Repeated bid treatment between Visit 3 and Visit 4.
Ticagrelor 0.563 mg/kg bid	Repeated bid treatment between Visit 3 and Visit 4.
Ticagrelor 0.75 mg/kg bid	Repeated bid treatment between Visit 3 and Visit 4.

Measured Values

	Ticagrelor 0.125 mg/kg	Ticagrelor 0.75 mg/kg	Ticagrelor 0.375 mg/kg	Ticagrelor 0.563 mg/kg	Ticagrelor 1.125 mg/kg	Ticagrelor 2.25 mg/kg	Ticagrelor 0.125 mg/kg bid	Ticagrelor 0.563 mg/kg bid	Ticagrelor 0.75 mg/kg bid
Number of Participants Analyzed [units:participants]	14	31	7	18	10	9	14	9	17
Assessment of Ticagrelor concentration - Part A [units: ng/mL] Geometric Mean (Standard Deviation)
Pre-dose							2.170 (Not applicable)^[1]	31.937 (48.6501)	28.066 (27.1344)
1 hour post-dose	12.713 (16.0627)	104.243 (103.1502)	34.069 (42.3746)	33.294 (55.4258)	182.558 (188.4254)	390.568 (294.2189)		80.414 (75.9675)	151.520 (116.0079)
2 hours post-dose	11.465 (8.7427)	107.729 (62.8343)	37.782 (31.6890)	74.626 (50.7053)	162.435 (161.8489)	426.804 (212.5385)	13.973 (15.3652)	102.166 (78.0785)	101.618 (65.2415)
4 hours post-dose	6.647 (4.4533)	75.907 (31.2786)	20.122 (9.9383)	51.005 (24.6435)	118.217 (42.0873)	188.383 (111.9267)
6 hours post-dose	3.663 (3.4061)	52.966 (29.0297)	19.435 (15.7259)	45.502 (17.8950)	69.708 (44.3168)	125.279 (89.0005)
8 hours post-dose	3.880 (3.3171)		15.699 (20.7596)	15.691 (15.1392)

No statistical analysis provided for Assessment of Ticagrelor concentration - Part A

8. Secondary Outcome Measure: Assessment of Ticagrelor concentration - Part B [ Time Frame: PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B. ]

Measure Type	Secondary
Measure Name	Assessment of Ticagrelor concentration - Part B
Measure Description
Time Frame	PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B.
Safety Issue?	No

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.
The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one single dose of ticagrelor were included in the safety population (SAF) for Part A. Analysis on the SAF was based on the study medication actually received.

Reporting Groups

	Description
Ticagrelor 0.125 mg/kg bid	Repeated bid treatment during Part B.

Measured Values

	Ticagrelor 0.125 mg/kg bid
Number of Participants Analyzed [units:participants]	9
Assessment of Ticagrelor concentration - Part B [units: ng/mL] Geometric Mean (Standard Deviation)
Pre-dose	2.478 (3.9580)
1 hour post-dose	9.677 (9.4275)
2 hours post-dose	14.144 (12.4711)
4 hours post-dose	9.605 (14.4979)

No statistical analysis provided for Assessment of Ticagrelor concentration - Part B

9. Secondary Outcome Measure: Assessment of AR-C124910XX concentration - Part A [ Time Frame: In conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7), after repeated dosing at Visit 4 (Day 14). Up to 8h post-dose (6h following protocol amendment, no pre-dose) Visit 2 and 3, up to 2h Visit 4 (pre-dose, 1h added following amendment) ]

Measure Type	Secondary
Measure Name	Assessment of AR-C124910XX concentration - Part A
Measure Description	AR-C124910XX is the active metabolite of Ticagrelor
Time Frame	In conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7), after repeated dosing at Visit 4 (Day 14). Up to 8h post-dose (6h following protocol amendment, no pre-dose) Visit 2 and 3, up to 2h Visit 4 (pre-dose, 1h added following amendment)
Safety Issue?	No

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.
The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one single dose of ticagrelor were included in the safety population (SAF) for Part A. Analysis on the SAF was based on the study medication actually received.

Reporting Groups

	Description
Ticagrelor 0.125 mg/kg	Single dose received at Visit 2.
Ticagrelor 0.75 mg/kg	Single dose received at Visit 2.
Ticagrelor 0.375 mg/kg	Single dose received at Visit 3.
Ticagrelor 0.563 mg/kg	Single dose received at Visit 3
Ticagrelor 1.125 mg/kg	Single dose received at Visit 3.
Ticagrelor 2.25 mg/kg	Single dose received at Visit 3.
Ticagrelor 0.125 mg/kg bid	Repeated bid treatment between Visit 3 and Visit 4.
Ticagrelor 0.563 mg/kg bid	Repeated bid treatment between Visit 3 and Visit 4.
Ticagrelor 0.75 mg/kg bid	Repeated bid treatment between Visit 3 and Visit 4.

Measured Values

	Ticagrelor 0.125 mg/kg	Ticagrelor 0.75 mg/kg	Ticagrelor 0.375 mg/kg	Ticagrelor 0.563 mg/kg	Ticagrelor 1.125 mg/kg	Ticagrelor 2.25 mg/kg	Ticagrelor 0.125 mg/kg bid	Ticagrelor 0.563 mg/kg bid	Ticagrelor 0.75 mg/kg bid
Number of Participants Analyzed [units:participants]	14	31	7	18	10	9	14	9	17
Assessment of AR-C124910XX concentration - Part A [units: ng/mL] Geometric Mean (Standard Deviation)
Pre-dose							1.250 (Not applicable)^[1]	17.380 (10.0399)	20.359 (15.0788)
1 hour post-dose	1.782 (1.6604)	16.302 (22.4614)	4.577 (7.8610)	3.708 (13.3332)	30.070 (44.2950)	63.088 (84.2091)		24.945 (15.6547)	43.986 (29.8127)
2 hours post-dose	2.681 (2.0733)	33.256 (25.3854)	11.757 (13.3322)	15.918 (17.4849)	52.932 (69.1056)	149.772 (71.3624)	4.026 (4.7624)	37.013 (32.7650)	44.690 (31.6577)
4 hours post-dose	2.071 (1.2770)	29.860 (13.8726)	7.630 (6.3730)	17.015 (7.9272)	50.887 (25.6964)	101.370 (44.6207)
6 hours post-dose	1.646 (1.0427)	25.276 (10.8318)	9.762 (2.3304)	16.703 (5.8115)	35.716 (22.3351)	76.941 (39.9167)
8 hours post-dose	1.715 (1.0226)		6.176 (6.3168)	9.232 (2.5385)

No statistical analysis provided for Assessment of AR-C124910XX concentration - Part A

10. Secondary Outcome Measure: Assessment of AR-C124910XX concentration - Part B [ Time Frame: PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B. ]

Measure Type	Secondary
Measure Name	Assessment of AR-C124910XX concentration - Part B
Measure Description	AR-C124910XX is the active metabolite of Ticagrelor
Time Frame	PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B.
Safety Issue?	No

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.
The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one single dose of ticagrelor were included in the safety population (SAF) for Part A. Analysis on the SAF was based on the study medication actually received.

Reporting Groups

	Description
Ticagrelor 0.125 mg/kg bid	Repeated bid treatment during Part B.

Measured Values

	Ticagrelor 0.125 mg/kg bid
Number of Participants Analyzed [units:participants]	9
Assessment of AR-C124910XX concentration - Part B [units: ng/mL] Geometric Mean (Standard Deviation)
Pre-dose	1.810 (1.1213)
1 hour post-dose	2.865 (1.6443)
2 hours post-dose	4.160 (3.1503)
4 hours post-dose	3.953 (4.1179)

No statistical analysis provided for Assessment of AR-C124910XX concentration - Part B

11. Secondary Outcome Measure: Oral Clearance (CL/F) - Part A [ Time Frame: PK measurements (up to 8 hours post-dose) are taken in conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7) and after repeated dosing at Visit 4 (Day 14). ]

Measure Type	Secondary
Measure Name	Oral Clearance (CL/F) - Part A
Measure Description	The PK parameter presented were derived using a model based analysis and not from a non-compartmental (NCA) analysis.
Time Frame	PK measurements (up to 8 hours post-dose) are taken in conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7) and after repeated dosing at Visit 4 (Day 14).
Safety Issue?	No

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.
The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one single dose of ticagrelor were included in the safety population (SAF) for Part A. Analysis on the SAF was based on the study medication actually received.

Reporting Groups

	Description
Overall	All patients receiving Ticagrelor during Part A.

Measured Values

	Overall
Number of Participants Analyzed [units:participants]	45
Oral Clearance (CL/F) - Part A [units: L/h] Geometric Mean (Standard Deviation)	22.50 (7.531)

No statistical analysis provided for Oral Clearance (CL/F) - Part A

12. Secondary Outcome Measure: Oral Clearance (CL/F) - Part B [ Time Frame: PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B. ]

Measure Type	Secondary
Measure Name	Oral Clearance (CL/F) - Part B
Measure Description	The PK parameter presented was derived using a model based analysis and not from a non-compartmental (NCA) analysis.
Time Frame	PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B.
Safety Issue?	No

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.
The PK analysis set is a subset of the safety analysis set, including all patients having at least one PK variable calculated. All patients who received at least one dose of randomised study drug, ticagrelor or placebo, will be included in the SAF for Part B. Analysis on the SAF was based on the study medication actually received.

Reporting Groups

	Description
Ticagrelor 0.125 mg/kg bid	Repeated bid treatment during Part B.

Measured Values

	Ticagrelor 0.125 mg/kg bid
Number of Participants Analyzed [units:participants]	9
Oral Clearance (CL/F) - Part B [units: L/h] Geometric Mean (Standard Deviation)	19.15 (6.673)

No statistical analysis provided for Oral Clearance (CL/F) - Part B

13. Secondary Outcome Measure: Number of vaso-occlusive crises - Part B [ Time Frame: During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6). ]

Measure Type	Secondary
Measure Name	Number of vaso-occlusive crises - Part B
Measure Description
Time Frame	During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).
Safety Issue?	No

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.
All patients randomised in Part B were to be included in the efficacy analysis set (EAS). Patients were analysed according to their randomised study medication.

Reporting Groups

	Description
Part B - Ticagrelor	Randomised treatment group for Part B of the study. Relevant for the Part B period.
Part B - Placebo	Randomised treatment group for Part B of the study. Relevant for the Part B period.

Measured Values

	Part B - Ticagrelor	Part B - Placebo
Number of Participants Analyzed [units:participants]	15	8
Number of vaso-occlusive crises - Part B [units: Number of events] Mean (Standard Deviation)	1.0 (2.00)	0.6 (0.74)

No statistical analysis provided for Number of vaso-occlusive crises - Part B

14. Secondary Outcome Measure: Number of vaso-occlusive crises requiring hospitalization or emergency department visits - Part B [ Time Frame: During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6). ]

Measure Type	Secondary
Measure Name	Number of vaso-occlusive crises requiring hospitalization or emergency department visits - Part B
Measure Description
Time Frame	During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).
Safety Issue?	No

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.
All patients randomised in Part B were to be included in the efficacy analysis set (EAS). Patients were analysed according to their randomised study medication.

Reporting Groups

	Description
Part B - Ticagrelor	Randomised treatment group for Part B of the study. Relevant for the Part B period.
Part B - Placebo	Randomised treatment group for Part B of the study. Relevant for the Part B period.

Measured Values

	Part B - Ticagrelor	Part B - Placebo
Number of Participants Analyzed [units:participants]	15	8
Number of vaso-occlusive crises requiring hospitalization or emergency department visits - Part B [units: Number of events] Mean (Standard Deviation)	0.2 (0.41)	0.1 (0.35)

No statistical analysis provided for Number of vaso-occlusive crises requiring hospitalization or emergency department visits - Part B

15. Secondary Outcome Measure: Percentage of days hospitalized for vaso-occlusice crisis or other complications of sickle cell disease - Part B [ Time Frame: During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6). ]

Measure Type	Secondary
Measure Name	Percentage of days hospitalized for vaso-occlusice crisis or other complications of sickle cell disease - Part B
Measure Description
Time Frame	During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).
Safety Issue?	No

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.
All patients randomised in Part B were to be included in the efficacy analysis set (EAS). Patients were analysed according to their randomised study medication.

Reporting Groups

	Description
Part B - Ticagrelor	Randomised treatment group for Part B of the study. Relevant for the Part B period.
Part B - Placebo	Randomised treatment group for Part B of the study. Relevant for the Part B period.

Measured Values

	Part B - Ticagrelor	Part B - Placebo
Number of Participants Analyzed [units:participants]	15	8
Percentage of days hospitalized for vaso-occlusice crisis or other complications of sickle cell disease - Part B [units: Percentage of days] Mean (Standard Deviation)	4.52 (11.816)	1.34 (3.788)

No statistical analysis provided for Percentage of days hospitalized for vaso-occlusice crisis or other complications of sickle cell disease - Part B

16. Secondary Outcome Measure: Percentage of days with pain (age >=4) - Part B [ Time Frame: During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6). ]

Measure Type	Secondary
Measure Name	Percentage of days with pain (age >=4) - Part B
Measure Description	Pain measured using the Faces Pain Scale, range 0-10 (0, 2, 4, 6, 8, 10), where 0 is no pain
Time Frame	During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).
Safety Issue?	No

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.
All patients randomised in Part B were to be included in the efficacy analysis set (EAS). Patients were analysed according to their randomised study medication.

Reporting Groups

	Description
Part B - Ticagrelor	Randomised treatment group for Part B of the study. Relevant for the Part B period.
Part B - Placebo	Randomised treatment group for Part B of the study. Relevant for the Part B period.

Measured Values

	Part B - Ticagrelor	Part B - Placebo
Number of Participants Analyzed [units:participants]	14	8
Percentage of days with pain (age >=4) - Part B [units: Percentage of days] Mean (Standard Deviation)	27.01 (34.065)	31.78 (23.731)

No statistical analysis provided for Percentage of days with pain (age >=4) - Part B

17. Secondary Outcome Measure: Mean intensity of pain (age >=4) - Part B [ Time Frame: During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6). ]

Measure Type	Secondary
Measure Name	Mean intensity of pain (age >=4) - Part B
Measure Description	Pain measured using the Faces Pain Scale, range 0-10 (0, 2, 4, 6, 8, 10), where 0 is no pain
Time Frame	During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).
Safety Issue?	No

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.
All patients randomised in Part B were to be included in the efficacy analysis set (EAS). Patients were analysed according to their randomised study medication.

Reporting Groups

	Description
Part B - Ticagrelor	Randomised treatment group for Part B of the study. Relevant for the Part B period.
Part B - Placebo	Randomised treatment group for Part B of the study. Relevant for the Part B period.

Measured Values

	Part B - Ticagrelor	Part B - Placebo
Number of Participants Analyzed [units:participants]	14	8
Mean intensity of pain (age >=4) - Part B [units: Mean score on scale] Mean (Standard Deviation)
Overall - Part B	1.40 (2.027)	0.87 (0.493)
1st week	1.64 (2.603)	1.36 (0.827)
2nd week	1.11 (2.236)	0.38 (0.525)
3rd week	1.06 (1.881)	0.67 (1.116)
4th week	1.46 (2.624)	0.83 (0.901)

No statistical analysis provided for Mean intensity of pain (age >=4) - Part B

18. Secondary Outcome Measure: Percentage of days of analgesic use (age >= 4) - Part B [ Time Frame: During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6). ]

Measure Type	Secondary
Measure Name	Percentage of days of analgesic use (age >= 4) - Part B
Measure Description
Time Frame	During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).
Safety Issue?	No

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.
All patients randomised in Part B were to be included in the efficacy analysis set (EAS). Patients were analysed according to their randomised study medication.

Reporting Groups

	Description
Part B - Ticagrelor	Randomised treatment group for Part B of the study. Relevant for the Part B period.
Part B - Placebo	Randomised treatment group for Part B of the study. Relevant for the Part B period.

Measured Values

	Part B - Ticagrelor	Part B - Placebo
Number of Participants Analyzed [units:participants]	14	8
Percentage of days of analgesic use (age >= 4) - Part B [units: Percentage of days] Mean (Standard Deviation)	16.79 (20.838)	18.56 (19.110)

No statistical analysis provided for Percentage of days of analgesic use (age >= 4) - Part B

19. Secondary Outcome Measure: Percentage of days of opioid analgesic use (age >=4) - Part B [ Time Frame: During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6). ]

Measure Type	Secondary
Measure Name	Percentage of days of opioid analgesic use (age >=4) - Part B
Measure Description
Time Frame	During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).
Safety Issue?	No

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.
All patients randomised in Part B were to be included in the efficacy analysis set (EAS). Patients were analysed according to their randomised study medication.

Reporting Groups

	Description
Part B - Ticagrelor	Randomised treatment group for Part B of the study. Relevant for the Part B period.
Part B - Placebo	Randomised treatment group for Part B of the study. Relevant for the Part B period.

Measured Values

	Part B - Ticagrelor	Part B - Placebo
Number of Participants Analyzed [units:participants]	14	8
Percentage of days of opioid analgesic use (age >=4) - Part B [units: Percentage of days] Mean (Standard Deviation)	12.46 (22.502)	0.54 (1.537)

No statistical analysis provided for Percentage of days of opioid analgesic use (age >=4) - Part B

20. Secondary Outcome Measure: Percentage of days of absence from school or work (age >=6) - Part B [ Time Frame: During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6). ]

Measure Type	Secondary
Measure Name	Percentage of days of absence from school or work (age >=6) - Part B
Measure Description
Time Frame	During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).
Safety Issue?	No

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.
All patients randomised in Part B were to be included in the efficacy analysis set (EAS). Patients were analysed according to their randomised study medication.

Reporting Groups

	Description
Part B - Ticagrelor	Randomised treatment group for Part B of the study. Relevant for the Part B period.
Part B - Placebo	Randomised treatment group for Part B of the study. Relevant for the Part B period.

Measured Values

	Part B - Ticagrelor	Part B - Placebo
Number of Participants Analyzed [units:participants]	11	6
Percentage of days of absence from school or work (age >=6) - Part B [units: Percentage of days] Mean (Standard Deviation)	4.87 (10.865)	5.95 (9.494)

No statistical analysis provided for Percentage of days of absence from school or work (age >=6) - Part B

21. Other Pre-specified Outcome Measure: Haemorrhagic events - Part A [ Time Frame: From randomisation to Part A (week 0) through Visit 4 (week 2) ]

Measure Type	Other Pre-specified
Measure Name	Haemorrhagic events - Part A
Measure Description
Time Frame	From randomisation to Part A (week 0) through Visit 4 (week 2)
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.
All patients who received at least one single dose of ticagrelor were included in the safety population (SAF) for Part A. Analysis on the SAF was based on the study medication actually received.

Reporting Groups

	Description
Part A - Ticagrelor	Randomised treatment group for Part A of the study. Relevant for the Part A period.

Measured Values

	Part A - Ticagrelor
Number of Participants Analyzed [units:participants]	45
Haemorrhagic events - Part A [units: Number of events]	0

No statistical analysis provided for Haemorrhagic events - Part A

22. Other Pre-specified Outcome Measure: Haemorrhagic events - Part B [ Time Frame: During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6). ]

Measure Type	Other Pre-specified
Measure Name	Haemorrhagic events - Part B
Measure Description
Time Frame	During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).
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.
All patients who received at least one dose of randomised study drug, ticagrelor or placebo, will be included in the SAF for Part B. Analysis on the SAF was based on the study medication actually received. Erroneously treated patients will be accounted for in the actual treatment group.

Reporting Groups

	Description
Part B - Ticagrelor	Randomised treatment group for Part B of the study. Relevant for the Part B period.
Part B - Placebo	Randomised treatment group for Part B of the study. Relevant for the Part B period.

Measured Values

	Part B - Ticagrelor	Part B - Placebo
Number of Participants Analyzed [units:participants]	16	7
Haemorrhagic events - Part B [units: Number of events]	0	0

No statistical analysis provided for Haemorrhagic events - Part B

Serious Adverse Events

Time Frame	SAEs were collected from Visit 1 and AEs from Visit 2. SAEs and Other AEs are presented by study period, where Part A consists of the time from randomization to Part A through Visit 4. Part B starts the day after Visit 4 and continues until Visit 8.
Additional Description	No text entered.

Reporting Groups

	Description
Part A - Ticagrelor	Randomised treatment group for Part A of the study. Relevant for the Part A period.
Part B - Ticagrelor	Randomised treatment group for Part B of the study. Relevant for the Part B period.
Part B - Placebo	Randomised treatment group for Part B of the study. Relevant for the Part B period.

Serious Adverse Events

Part A - Ticagrelor

Part B - Ticagrelor

Part B - Placebo

Total, serious adverse events

# participants affected / at risk

5/45 (11.11%)

4/16 (25.00%)

1/7 (14.29%)

Blood and lymphatic system disorders

Sickle cell anemia with crisis¹,^†

# participants affected / at risk

3/45 (6.67%)

3/16 (18.75%)

1/7 (14.29%)

# events

Infections and infestations

Gastroenteritis viral¹,^†

# participants affected / at risk

1/45 (2.22%)

0/16 (0.00%)

0/7 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Acute chest syndrome¹,^†

# participants affected / at risk

1/45 (2.22%)

1/16 (6.25%)

0/7 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA version 19.1

Other Adverse Events

Time Frame	SAEs were collected from Visit 1 and AEs from Visit 2. SAEs and Other AEs are presented by study period, where Part A consists of the time from randomization to Part A through Visit 4. Part B starts the day after Visit 4 and continues until Visit 8.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Part A - Ticagrelor	Randomised treatment group for Part A of the study. Relevant for the Part A period.
Part B - Ticagrelor	Randomised treatment group for Part B of the study. Relevant for the Part B period.
Part B - Placebo	Randomised treatment group for Part B of the study. Relevant for the Part B period.

Other Adverse Events

Part A - Ticagrelor

Part B - Ticagrelor

Part B - Placebo

Total, other (not including serious) adverse events

# participants affected / at risk

22/45 (48.89%)

12/16 (75.00%)

5/7 (71.43%)

Blood and lymphatic system disorders

Sickle cell anemia with crisis¹,^†

# participants affected / at risk

6/45 (13.33%)

1/16 (6.25%)

1/7 (14.29%)

# events

Ear and labyrinth disorders

Tympanic membrane perforation¹,^†

# participants affected / at risk

0/45 (0.00%)

1/16 (6.25%)

0/7 (0.00%)

# events

Gastrointestinal disorders

Abdominal pain¹,^†

# participants affected / at risk

6/45 (13.33%)

3/16 (18.75%)

2/7 (28.57%)

# events

Gastrointestinal disorders

Abdominal pain upper¹,^†

# participants affected / at risk

0/45 (0.00%)

2/16 (12.50%)

0/7 (0.00%)

# events

Gastrointestinal disorders

Gastritis¹,^†

# participants affected / at risk

0/45 (0.00%)

0/16 (0.00%)

1/7 (14.29%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

0/45 (0.00%)

1/16 (6.25%)

0/7 (0.00%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

0/45 (0.00%)

3/16 (18.75%)

0/7 (0.00%)

# events

General disorders

Chest discomfort¹,^†

# participants affected / at risk

0/45 (0.00%)

1/16 (6.25%)

0/7 (0.00%)

# events

General disorders

Facial pain¹,^†

# participants affected / at risk

2/45 (4.44%)

1/16 (6.25%)

1/7 (14.29%)

# events

General disorders

Non-cardiac chest pain¹,^†

# participants affected / at risk

2/45 (4.44%)

1/16 (6.25%)

1/7 (14.29%)

# events

General disorders

Pain¹,^†

# participants affected / at risk

0/45 (0.00%)

1/16 (6.25%)

0/7 (0.00%)

# events

General disorders

Pyrexia¹,^†

# participants affected / at risk

1/45 (2.22%)

2/16 (12.50%)

0/7 (0.00%)

# events

Infections and infestations

Conjunctivitis¹,^†

# participants affected / at risk

0/45 (0.00%)

0/16 (0.00%)

1/7 (14.29%)

# events

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

0/45 (0.00%)

1/16 (6.25%)

0/7 (0.00%)

# events

Infections and infestations

Otitis media¹,^†

# participants affected / at risk

0/45 (0.00%)

1/16 (6.25%)

0/7 (0.00%)

# events

Infections and infestations

Pharyngitis¹,^†

# participants affected / at risk

0/45 (0.00%)

1/16 (6.25%)

0/7 (0.00%)

# events

Infections and infestations

Tinea infection¹,^†

# participants affected / at risk

0/45 (0.00%)

1/16 (6.25%)

0/7 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

5/45 (11.11%)

4/16 (25.00%)

2/7 (28.57%)

# events

Musculoskeletal and connective tissue disorders

Back pain¹,^†

# participants affected / at risk

3/45 (6.67%)

2/16 (12.50%)

1/7 (14.29%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal pain¹,^†

# participants affected / at risk

1/45 (2.22%)

2/16 (12.50%)

1/7 (14.29%)

# events

Musculoskeletal and connective tissue disorders

Neck pain¹,^†

# participants affected / at risk

0/45 (0.00%)

1/16 (6.25%)

0/7 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Pain in extremity¹,^†

# participants affected / at risk

5/45 (11.11%)

3/16 (18.75%)

2/7 (28.57%)

# events

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

1/45 (2.22%)

1/16 (6.25%)

0/7 (0.00%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

4/45 (8.89%)

0/16 (0.00%)

2/7 (28.57%)

# events

Reproductive system and breast disorders

Pelvic pain¹,^†

# participants affected / at risk

0/45 (0.00%)

0/16 (0.00%)

1/7 (14.29%)

# events

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

1/45 (2.22%)

2/16 (12.50%)

0/7 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Oropharyngeal pain¹,^†

# participants affected / at risk

1/45 (2.22%)

3/16 (18.75%)

0/7 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA version 19.1

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: No publication can be made in advance of the first multicenter publication by the sponsor. Any publication will be submitted to the sponsor for review prior to the being published. The sponsor has the right to defer this publication for a period between 60 days to 6 months. The sponsor has the right to restrict the use of confidential information in any of the publications submitted.

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:	Brilinta Global Clinical Lead
Organization:	AstraZeneca
Phone	+46 31 776 1000
E-mail:	[email protected]

Documents available

d5136c00007 CSP
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D5136C00007_SAP
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Trial Results Summaries
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AstraZeneca Clinical Study Information Center

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information.center@astrazeneca.com

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d5136c00007 CSP

D5136C00007_SAP

Trial Results Summaries