Clinical Trial Results:
A Phase 2, Placebo Controlled, Randomized, Double-Blind, Parallel-Arm Study to Evaluate Efficacy and Safety of BMS- 986141 For the Prevention of Recurrent Brain Infarction in Subjects Receiving Acetylsalicylic Acid (ASA) Following Acute Ischemic Stroke or Transient Ischemic Attack
Summary
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EudraCT number |
2015-003959-22 |
Trial protocol |
ES |
Global end of trial date |
31 Mar 2017
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Results information
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Results version number |
v1 |
This version publication date |
15 Apr 2018
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First version publication date |
15 Apr 2018
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Other versions |
v2 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CV006-004
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02671461 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Bristol-Myers Squibb
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Sponsor organisation address |
Chaussée de la Hulpe 185, Brussels, Belgium, 1170
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Public contact |
EU Study Start-Up Unit, Bristol-Myers Squibb International Corporation, clinical.trials@bms.com
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Scientific contact |
Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, Clinical.Trials@bms.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
31 Mar 2017
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Mar 2017
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To determine the dose-response relationship of BMS-986141 on the recurrence of brain infarction at 28 days as assessed by a composite of symptomatic ischemic stroke and unrecognized brain infarction as assessed by MRI in subjects with ischemic stroke or TIA treated with ASA.
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
14 Sep 2016
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 16
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Worldwide total number of subjects |
16
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
10
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From 65 to 84 years |
6
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
16 subjects were enrolled; 15 were treated. 1 subject was not randomized because the interactive voice response system did not work at the time of enrollment | ||||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | ||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo | ||||||||||||||||||||||||||||||||
Arm description |
Matching placebo was taken once daily. Administration was exactly the same as for BMS-986141 | ||||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Matching Placebo for BMS-986141 QD for up to 28 days
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Arm title
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BMS-986141 0.8 mg | ||||||||||||||||||||||||||||||||
Arm description |
BMS-986141 0.8 mg QD for up to 28 days | ||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||
Investigational medicinal product name |
BMS-986141
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
0.8 mg BMS-986141 QD for up to 28 days
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Arm title
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BMS-986141 4.8 mg | ||||||||||||||||||||||||||||||||
Arm description |
BMS-986141 4.8 mg QD for up to 28 days | ||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||
Investigational medicinal product name |
BMS-986141
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
4.8 mg BMS-986141 QD for up to 28 days
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Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: 16 subjects were enrolled; 15 were treated. 1 subject was not randomized because the interactive voice response system did not work at the time of enrollment [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: 16 subjects were enrolled; 15 were treated. 1 subject was not randomized because the interactive voice response system did not work at the time of enrollment [3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: 16 subjects were enrolled; 15 were treated. 1 subject was not randomized because the interactive voice response system did not work at the time of enrollment |
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Baseline characteristics reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Matching placebo was taken once daily. Administration was exactly the same as for BMS-986141 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
BMS-986141 0.8 mg
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Reporting group description |
BMS-986141 0.8 mg QD for up to 28 days | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
BMS-986141 4.8 mg
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Reporting group description |
BMS-986141 4.8 mg QD for up to 28 days | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Matching placebo was taken once daily. Administration was exactly the same as for BMS-986141 | ||
Reporting group title |
BMS-986141 0.8 mg
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Reporting group description |
BMS-986141 0.8 mg QD for up to 28 days | ||
Reporting group title |
BMS-986141 4.8 mg
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Reporting group description |
BMS-986141 4.8 mg QD for up to 28 days |
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End point title |
Number of subjects with composite of symptomatic ischemic stroke by Day 28 and unrecognized brain infarction assessed by MRI at Day 28 [1] | ||||||||||||
End point description |
The incidence of a composite of symptomatic ischemic stroke by Day 28 and unrecognized brain infarction assessed by MRI at Day 28 was to be reported by arm in all treated subjects.
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End point type |
Primary
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End point timeframe |
28 Days
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only summary statistics were planned for this outcome measure; Insufficient data available to perform analysis due to study termination |
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Notes [2] - Insufficient data available to perform analysis due to study termination [3] - Insufficient data available to perform analysis due to study termination [4] - Insufficient data available to perform analysis due to study termination |
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No statistical analyses for this end point |
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End point title |
Percentage of subjects with composite of adjudicated major bleeding and adjudicated clinically relevant non-major (CRNM) bleeding during the treatment period [5] | ||||||||||||||||
End point description |
The proportion of subjects with composite of major bleeding and CRNM bleeding was to be reported. Point estimates and 95% CIs for event rates were to be presented by treatment, together with point estimates and 95% CIs for the difference of event rates between each BMS-986141 arm and placebo.
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End point type |
Primary
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End point timeframe |
Up to 90 days
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Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only summary statistics were planned for this outcome measure; Insufficient data available to perform analysis due to study termination |
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Notes [6] - Insufficient data available to perform analysis due to study termination [7] - Insufficient data available to perform analysis due to study termination [8] - Insufficient data available to perform analysis due to study termination |
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No statistical analyses for this end point |
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End point title |
Percentage of subjects with major adverse cardiovascular events (MACE) | ||||||||||||||||
End point description |
MACE was defined as a composite of adjudicated recurrent stroke, myocardial infarction, or cardiovascular death. The percentage of treated subjects experiencing these events at Day 90 was to be reported by arm.
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End point type |
Secondary
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End point timeframe |
90 days
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Notes [9] - Insufficient data available to perform analysis due to study termination [10] - Insufficient data available to perform analysis due to study termination [11] - Insufficient data available to perform analysis due to study termination |
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No statistical analyses for this end point |
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End point title |
Percentage of subjects with adjudicated symptomatic recurrent stroke (including fatal and non-fatal) | ||||||||||||||||
End point description |
The percentage of subjects with adjudicated symptomatic recurrent stroke at Day 28 was to be reported by arm for all treated subjects.
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End point type |
Secondary
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End point timeframe |
Day 28
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Notes [12] - Insufficient data available to perform analysis due to study termination [13] - Insufficient data available to perform analysis due to study termination [14] - Insufficient data available to perform analysis due to study termination |
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No statistical analyses for this end point |
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End point title |
Percentage of subjects with composite of unrecognized brain infarction assessed by MRI at Day 28 and MACE at Day 90 | ||||||||||||||||
End point description |
The percentage of subjects with unrecognized brain infarction at Day 28 and MACE at Day 90 was to be reported by arm for all treated subjects.
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End point type |
Secondary
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End point timeframe |
Day 90
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Notes [15] - Insufficient data available to perform analysis due to study termination [16] - Insufficient data available to perform analysis due to study termination [17] - Insufficient data available to perform analysis due to study termination |
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No statistical analyses for this end point |
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End point title |
Percentage of subjects composite of adjudicated recurrent ischemic stroke, myocardial infarction, or cardiovascular death | ||||||||||||||||
End point description |
The percentage of treated subjects with composite of adjudicated recurrent ischemic stroke, myocardial infarction, or cardiovascular death was reported by arm.
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End point type |
Secondary
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End point timeframe |
Day 90
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Notes [18] - Insufficient data available to perform analysis due to study termination [19] - Insufficient data available to perform analysis due to study termination [20] - Insufficient data available to perform analysis due to study termination |
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
From first dose until 30 days following last dose (assessed up to March 2017, approximately 6 months)
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.1
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Reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Matching placebo was taken once daily. Administration was exactly the same as for BMS-986141 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
BMS-986141 4.8 mg
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Reporting group description |
BMS-986141 4.8 mg QD for up to 28 days | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
BMS-986141 0.8 mg
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Reporting group description |
BMS-986141 0.8 mg QD for up to 28 days | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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07 Jul 2016 |
Changed top dose to be studied from 16 mg QD to 8 mg QD. Initiation of the 8 mg dose group will only begin following DMC review of safety and laboratory data from the Day 28 study visit for at least 10% of total planned subjects. Changes were made to some exclusion criteria to
minimize subject risk. Guidance around the use of CYP3A4 inhibitors
and inducers has been further clarified. The statistical sections and sample size calculations have been updated to correspond to these changes. PK sampling windows were expanded; changed requirements for contraception to be the use of one highly effective method of contraception or one less effective method of contraception; added statement to Appendix 1 that local laws and regulations may require use of alternative and/or additional contraception methods; clarified genotyping testing; provided further clarifications to assist with study
implementation; updated text per new BMS protocol model document template; corrected typographical errors. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |