Phase III study of ICI35,868 (Diprivan) with and without EES0000645/A (SDS) on gastrointestinal endoscopy - Kagami_SDS

Study identifier:D0092C00002

ClinicalTrials.gov identifier:NCT01961349

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A multi-centre, double-blind, randomised, parallel-group, placebo-controlled, phase III confirmatory study to assess efficacy and safety of the moderate sedation of ICI35,868 with and without EES0000645/A on gastrointestinal endoscopy

Medical condition

Sedation to be moderate for a diagnostic gastrointestinal endoscopy and gastrointestinal endoscopic polypectomy

Phase

Phase 3

Healthy volunteers

Study drug

Intralipid, ICI35,868 (Diprivan), ICI35,868 (Diprivan) + EES0000645/A (SDS)

Sex

All

Actual Enrollment

279

Study type

Interventional

Age

20 Years +

Date

Study Start Date: 01 Oct 2013

Primary Completion Date: 01 Mar 2014

Study Completion Date: 01 Mar 2014

Study design

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

Verification:

Verified 01 Oct 2015 by AstraZeneca

Collaborators

Johnson & Johnson

Inclusion and exclusion criteria

Location

Research Site

Shinjuku-ku, Japan

Location

Research Site

Moriya-shi, Japan

Location

Research Site

Yokohama-shi, Japan

Arms	Assigned Interventions
Placebo Comparator: Group 1 Group 1 (placebo group) is treated by Anaesthesiologist	Drug: Intralipid Treated by Anaesthesiologist. (Intralipid is being used as a placebo for Diprivan.)
Active Comparator: Group 2 Group 2 (ICI35,868 without EES0000645/A) is treated by Anaesthesiologist	Drug: ICI35,868 (Diprivan) Treated by Anaesthesiologist
Active Comparator: Group 3 Group 3 (ICI35,868 with EES0000645/A) is treated by Endoscopist	Drug: ICI35,868 (Diprivan) + EES0000645/A (SDS) Treated by Endoscopist with EES0000645/A(SDS)

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Of the 279 consented subjects, 7 were excluded after screening.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
NA

Reporting Groups

	Description
Placebo	Placebo administered by the anaesthesiologist without EES0000645/A
ICI35,868 without EES0000645/A	ICI35,868 administered by the anaesthesiologist without EES0000645/A
ICI35,868 with EES0000645/A	ICI35,868 administered and EES0000645/A operated by the GI physician or the nurse

Participant Flow: Overall Study

	Placebo	ICI35,868 without EES0000645/A	ICI35,868 with EES0000645/A
STARTED	54	107	111
COMPLETED	51	101	109
NOT COMPLETED	3	6	2
Withdrawal by Subject	1	4	0
Adverse Event	0	0	1
registration error, personal reason etc	2	2	1

Baseline Characteristics

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

Reporting Groups

	Description
Placebo	Placebo administered by the anaesthesiologist without EES0000645/A
ICI35,868 without EES0000645/A	ICI35,868 administered by the anaesthesiologist without EES0000645/A
ICI35,868 with EES0000645/A	ICI35,868 administered and EES0000645/A operated by the GI physician or the nurse

Baseline Measures

	Placebo	ICI35,868 without EES0000645/A	ICI35,868 with EES0000645/A	Total
Number of Participants [units: Participants]	51	101	109	261
Age Continuous [units: years] Mean ± Standard Deviation	58.6 ± 14.3	55.4 ± 12.9	57.2 ± 14.8	56.8 ± 14.0
Gender, Male/Female [units: Participants]
Male	34	65	75	174
Female	17	36	34	87

Outcome Measures

1. Primary Outcome Measure: Achivement of target sedation [ Time Frame: from scope-in to scope-out ]

Measure Type	Primary
Measure Name	Achivement of target sedation
Measure Description	The target sedation is defined as MOAA/S (Modified Observer's Assessment of Alertness/Sedation) scores 2 to 4 for ≥50% of all MOAA/S measurements from scope-in to scope-out.
Time Frame	from scope-in to scope-out
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.
FAS (Full Analysis Set)

Reporting Groups

	Description
Placebo	Placebo administered by the anaesthesiologist without EES0000645/A
ICI35,868 without EES0000645/A	ICI35,868 administered by the anaesthesiologist without EES0000645/A
ICI35,868 with EES0000645/A	ICI35,868 administered and EES0000645/A operated by the GI physician or the nurse

Measured Values

	Placebo	ICI35,868 without EES0000645/A	ICI35,868 with EES0000645/A
Number of Participants Analyzed [units:participants]	51	101	109
Achivement of target sedation [units: % of patients] Number (95% Confidence Interval)	21.6 (11.3 to 35.3)	88.1 (80.2 to 93.7)	94.5 (88.4 to 98.0)

Statistical Analysis 1 for Achivement of target sedation

Groups^[1]	Placebo, ICI35,868 without EES0000645/A
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Fisher Exact
P-Value^[4]	<0.001

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

Statistical Analysis 2 for Achivement of target sedation

Groups^[1]	Placebo, ICI35,868 with EES0000645/A
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Fisher Exact
P-Value^[4]	<0.001

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

2. Secondary Outcome Measure: PSSI total score [ Time Frame: at 24-48 h after endoscopy ]

Measure Type	Secondary
Measure Name	PSSI total score
Measure Description	PSSI (Statistics of Patient Satisfaction with Sedation Instrument) total score obtained from 20 questions (1 to 7 points for each) adjusted to have range of 0 ( very dissatisfied: all items scored with 1 point) to 100 (very satisfied: all items scored with 7 points)
Time Frame	at 24-48 h after endoscopy
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.
FAS (Full Analysis Set)

Reporting Groups

	Description
Placebo	Placebo administered by the anaesthesiologist without EES0000645/A
ICI35,868 without EES0000645/A	ICI35,868 administered by the anaesthesiologist without EES0000645/A
ICI35,868 with EES0000645/A	ICI35,868 administered and EES0000645/A operated by the GI physician or the nurse

Measured Values

	Placebo	ICI35,868 without EES0000645/A	ICI35,868 with EES0000645/A
Number of Participants Analyzed [units:participants]	51	101	109
PSSI total score [units: Score on a scale (0 - 100)] Mean (Standard Deviation)	65.3 (19.7)	81.2 (12.5)	80.8 (14.1)

Statistical Analysis 1 for PSSI total score

Groups^[1]	Placebo, ICI35,868 without EES0000645/A
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANOVA
P-Value^[4]	<0.001

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

Statistical Analysis 2 for PSSI total score

Groups^[1]	Placebo, ICI35,868 with EES0000645/A
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANOVA
P-Value^[4]	<0.001

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

Serious Adverse Events

Time Frame	3 days
Additional Description	NA

Reporting Groups

	Description
Placebo	Placebo administered by the anaesthesiologist without EES0000645/A
ICI35,868 without EES0000645/A	ICI35,868 administered by the anaesthesiologist without EES0000645/A
ICI35,868 with EES0000645/A	ICI35,868 administered and EES0000645/A operated by the GI physician or the nurse

Serious Adverse Events

	Placebo	ICI35,868 without EES0000645/A	ICI35,868 with EES0000645/A
Total, serious adverse events
# participants affected / at risk	0/51 (0.00%)	0/101 (0.00%)	0/109 (0.00%)

Other Adverse Events

Time Frame	3 days
Additional Description	NA

Frequency Threshold

Threshold above which other adverse events are reported	1.8%

Reporting Groups

	Description
Placebo	Placebo administered by the anaesthesiologist without EES0000645/A
ICI35,868 without EES0000645/A	ICI35,868 administered by the anaesthesiologist without EES0000645/A
ICI35,868 with EES0000645/A	ICI35,868 administered and EES0000645/A operated by the GI physician or the nurse

Other Adverse Events

Placebo

ICI35,868 without EES0000645/A

ICI35,868 with EES0000645/A

Total, other (not including serious) adverse events

# participants affected / at risk

9/51 (17.65%)

7/101 (6.93%)

12/109 (11.01%)

Psychiatric disorders

disinhibition¹

# participants affected / at risk

0/51 (0.00%)

2/101 (1.98%)

2/109 (1.83%)

# events

Investigations

blood urine present¹

# participants affected / at risk

1/51 (1.96%)

2/101 (1.98%)

3/109 (2.75%)

# events

Nervous system disorders

sedation¹

# participants affected / at risk

0/51 (0.00%)

1/101 (0.99%)

3/109 (2.75%)

# events

Investigations

oxygen saturation decreased¹

# participants affected / at risk

1/51 (1.96%)

0/101 (0.00%)

2/109 (1.83%)

# events

Gastrointestinal disorders

Abdominal distension¹

# participants affected / at risk

2/51 (3.92%)

1/101 (0.99%)

0/109 (0.00%)

# events

Gastrointestinal disorders

Abdominal pain lower¹

# participants affected / at risk

5/51 (9.80%)

1/101 (0.99%)

2/109 (1.83%)

# events

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

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:

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
NA

Results Point of Contact

Name/Title:	Hideo Negi
Organization:	CO RI&A TA, R&D
Phone	+81 6 4803 3533 Ext: 4716
E-mail:	[email protected]

Documents available

D0092C00002_CSR_Synopsis.pdf
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

D0092C00002_CSR_Synopsis.pdf

Trial Results Summaries