Safety and Efficacy Study of a Protease Activated Receptor-4 Antagonist Being Tested to Reduce the Chances of Having Additional Strokes or "Mini Strokes"

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02671461
• Collaborator: (none)
• Enrollment: 16
• Locations: 33
• Arms: 3
• Actual Duration (Months): 11.2
• Patients Per Site: 0.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether BMS-986141 is effective in reducing the recurrence of stroke in people who recently had a stroke, or a transient ischemic attack (known as a TIA or "mini stroke") and are receiving acetylsalicylic acid (also known as aspirin or ASA) to treat the stroke or TIA.

Condition or Disease	Intervention/Treatment	Phase
Thrombosis	Drug: BMS-986141; Drug: Aspirin; Other: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Apr 25, 2016
• Actual Primary Completion Date: Mar 31, 2017
• Actual Study Completion Date: Mar 31, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BMS-986141 0.8mg BMS-986141 0.8mg orally (tablets) and Aspirin (ASA) 75 to 162 mg orally (tablets)	Drug: BMS-986141; Drug: Aspirin
Experimental: BMS-986141 4.8mg BMS-986141 4.8mg orally (tablets) and ASA 75 to 162 mg orally (tablets)	Drug: BMS-986141; Drug: Aspirin
Placebo Comparator: Placebo Placebo orally (tablets) and ASA 75 to 162 mg orally (tablets)	Drug: Aspirin; Other: Placebo

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Composite of Symptomatic Ischemic Stroke by Day 28 and Unrecognized Brain Infarction Assessed by MRI at Day 28 [28 Days]

   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 participants.

2. Percentage of Participants With Composite of Adjudicated Major Bleeding and Adjudicated Clinically Relevant Non-major (CRNM) Bleeding During the Treatment Period [Up to 90 days]

   The percentage of participants 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.

Secondary Outcome Measures

1. Percentage of Participants With Major Adverse Cardiovascular Events (MACE) [90 days]

   MACE was defined as a composite of adjudicated recurrent stroke, myocardial infarction, or cardiovascular death. The percentage of treated participants experiencing these events at Day 90 was to be reported by arm.

2. Percentage of Participants With Adjudicated Symptomatic Recurrent Stroke (Including Fatal and Non-fatal) [Day 28]

   The percentage of participants with adjudicated symptomatic recurrent stroke at Day 28 was to be reported by arm for all treated participants.

3. Percentage of Participants With Composite of Unrecognized Brain Infarction Assessed by MRI at Day 28 and MACE at Day 90 [Day 90]

   The percentage of participants with unrecognized brain infarction at Day 28 and MACE at Day 90 was to be reported by arm for all treated participants.

4. Percentage of Participants Composite of Adjudicated Recurrent Ischemic Stroke, Myocardial Infarction, or Cardiovascular Death [Day 90]

   The percentage of treated participants with composite of adjudicated recurrent ischemic stroke, myocardial infarction, or cardiovascular death was reported by arm.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Male or female, age 18 or older

• Must have had a very recent stroke or transient ischemic attack ("mini stroke") that can be confirmed by the study doctor

• Able to be assigned to a study group no later than 48 hours after the stroke occurred

• Has an image of the brain that confirms that the stroke was not caused by hemorrhage or other reason that could explain symptoms

Exclusion Criteria:

• A suspicion by the study doctor that the transient ischemic attack or stroke was caused by a blood clot that formed in the heart; examples of this include history of an abnormal heart rhythm known as atrial fibrillation or a ventricular aneurysm or defect of the heart.

• Any condition requiring treatment with an anticoagulant

• History of intracranial hemorrhage ("bleeding in the brain")

• Gastrointestinal ("stomach or intestinal") bleeding in the last 3 months that required treatment

• Planned or anticipated invasive surgery or procedure during the study

• Unable to tolerate MRI procedures.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Banner University Medical Ctr	Phoenix	Arizona	United States	85006
2	Hoag Memorial Hospital	Newport Beach	California	United States	92658
3	Local Institution	Newark	Delaware	United States	19718
4	University Of Florida	Gainesville	Florida	United States	32610
5	University Of Florida Hsc/Jacksonville	Jacksonville	Florida	United States	32209
6	Florida Hospital	Orlando	Florida	United States	32803
7	Intercoastal Medical Group	Sarasota	Florida	United States	34239
8	Presence Saint Joseph Medical Center	Joliet	Illinois	United States	64035
9	University Of Louisville	Louisville	Kentucky	United States	40202
10	Local Institution	Baltimore	Maryland	United States	21215
11	Tufts Medical Center	Boston	Massachusetts	United States	02111
12	Boston Medical Center	Boston	Massachusetts	United States	02118
13	St. Lukes Marion Bloch Neuroscience Institute	Kansas City	Missouri	United States	64111
14	Advanced Neurology Specialists	Great Falls	Montana	United States	59405
15	Local Institution	Omaha	Nebraska	United States	68105
16	JFK Medical Center	Edison	New Jersey	United States	08820-3947
17	Local Institution	Chapel Hill	North Carolina	United States	27599
18	Duke University Medical Center	Durham	North Carolina	United States	27710
19	Guilford Medical Associates, Pa	Greensboro	North Carolina	United States	27405
20	Providence Portland Med Ctr	Portland	Oregon	United States	97225
21	Providence St Vincent Medical Center	Portland	Oregon	United States	97225
22	Oregon Health Science Univ	Portland	Oregon	United States	97239
23	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
24	York Hospital	York	Pennsylvania	United States	17403
25	Medical University Of South Carolina	Charleston	South Carolina	United States	29425
26	Local Institution	Memphis	Tennessee	United States	38103
27	West Virginia University	Morgantown	West Virginia	United States	26505
28	Local Institution	Nagoya	Aichi	Japan	4600001
29	Local Institution	Sapporo-shi	Hokkaido	Japan	0608570
30	Local Institution	Kobe-shi	Hyogo	Japan	6500047
31	Local Institution	Sendai-shi	Miyagi	Japan	982-8523
32	Local Institution	Hidaka-shi	Saitama	Japan	3501298
33	Local Institution	Fukuoka		Japan	810-0001

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

• Study Director: Bristol Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

• Statistical Analysis Plan - Nov 19, 2015
• Study Protocol - Jul 7, 2016

More Information

Additional Information:

• BMS Clinical Trial Patient Recruiting

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT02671461
• Other Study ID Numbers: CV006-004
• First Posted: Feb 2, 2016
• Last Update Posted: Dec 14, 2018
• Last Verified: Dec 1, 2018

• Additional relevant MeSH terms: Thrombosis; Aspirin

Study Results

Participant Flow

Pre-assignment Detail	16 participants were enrolled; 15 were randomized; 14 were treated. 1 participant was not randomized because the interactive voice response system did not work at the time of enrollment

Arm/Group Title	Placebo	BMS-986141 0.8 mg	BMS-986141 4.8 mg
Arm/Group Description	Matching placebo was taken once daily. Administration was exactly the same as for BMS-986141	BMS-986141 0.8 mg QD for up to 28 days	BMS-986141 4.8 mg QD for up to 28 days
Period Title: Treatment
STARTED	3	5	7
COMPLETED	1	2	2
NOT COMPLETED	2	3	5
Period Title: Treatment
STARTED	2	5	7
COMPLETED	1	4	6
NOT COMPLETED	1	1	1

Baseline Characteristics

Arm/Group Title	Placebo	BMS-986141 0.8 mg	BMS-986141 4.8 mg	Total
Arm/Group Description	Matching placebo was taken once daily. Administration was exactly the same as for BMS-986141	BMS-986141 0.8 mg QD for up to 28 days	BMS-986141 4.8 mg QD for up to 28 days	Total of all reporting groups
Overall Participants	3	5	7	15
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.3 (9.2)	64.8 (12.2)	66.7 (7.6)	65.4 (9.0)
Sex: Female, Male (Count of Participants)
Female	1 33.3%	1 20%	3 42.9%	5 33.3%
Male	2 66.7%	4 80%	4 57.1%	10 66.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	3 100%	5 100%	7 100%	15 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	1 14.3%	1 6.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	2 40%	1 14.3%	3 20%
White	3 100%	3 60%	5 71.4%	11 73.3%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Composite of Symptomatic Ischemic Stroke by Day 28 and Unrecognized Brain Infarction Assessed by MRI at Day 28
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 participants.
Time Frame	28 Days

Outcome Measure Data

Analysis Population Description

Insufficient data available to perform analysis due to study termination

Arm/Group Title	Placebo	BMS-986141 0.8 mg	BMS-986141 4.8 mg
Arm/Group Description	Matching placebo was taken once daily. Administration was exactly the same as for BMS-986141	BMS-986141 0.8 mg QD for up to 28 days	BMS-986141 4.8 mg QD for up to 28 days
Measure Participants	0	0	0

2. Primary Outcome

Title	Percentage of Participants With Composite of Adjudicated Major Bleeding and Adjudicated Clinically Relevant Non-major (CRNM) Bleeding During the Treatment Period
Description	The percentage of participants 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.
Time Frame	Up to 90 days

Outcome Measure Data

Analysis Population Description

Insufficient data available to perform analysis due to study termination

Arm/Group Title	Placebo	BMS-986141 0.8 mg	BMS-986141 4.8 mg
Arm/Group Description	Matching placebo was taken once daily. Administration was exactly the same as for BMS-986141	BMS-986141 0.8 mg QD for up to 28 days	BMS-986141 4.8 mg QD for up to 28 days
Measure Participants	0	0	0

3. Secondary Outcome

Title	Percentage of Participants With Major Adverse Cardiovascular Events (MACE)
Description	MACE was defined as a composite of adjudicated recurrent stroke, myocardial infarction, or cardiovascular death. The percentage of treated participants experiencing these events at Day 90 was to be reported by arm.
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

Insufficient data available to perform analysis due to study termination

Arm/Group Title	Placebo	BMS-986141 0.8 mg	BMS-986141 4.8 mg
Arm/Group Description	Matching placebo was taken once daily. Administration was exactly the same as for BMS-986141	BMS-986141 0.8 mg QD for up to 28 days	BMS-986141 4.8 mg QD for up to 28 days
Measure Participants	0	0	0

4. Secondary Outcome

Title	Percentage of Participants With Adjudicated Symptomatic Recurrent Stroke (Including Fatal and Non-fatal)
Description	The percentage of participants with adjudicated symptomatic recurrent stroke at Day 28 was to be reported by arm for all treated participants.
Time Frame	Day 28

Outcome Measure Data

Analysis Population Description

Insufficient data available to perform analysis due to study termination

Arm/Group Title	Placebo	BMS-986141 0.8 mg	BMS-986141 4.8 mg
Arm/Group Description	Matching placebo was taken once daily. Administration was exactly the same as for BMS-986141	BMS-986141 0.8 mg QD for up to 28 days	BMS-986141 4.8 mg QD for up to 28 days
Measure Participants	0	0	0

5. Secondary Outcome

Title	Percentage of Participants With Composite of Unrecognized Brain Infarction Assessed by MRI at Day 28 and MACE at Day 90
Description	The percentage of participants with unrecognized brain infarction at Day 28 and MACE at Day 90 was to be reported by arm for all treated participants.
Time Frame	Day 90

Outcome Measure Data

Analysis Population Description

Insufficient data available to perform analysis due to study termination

Arm/Group Title	Placebo	BMS-986141 0.8 mg	BMS-986141 4.8 mg
Arm/Group Description	Matching placebo was taken once daily. Administration was exactly the same as for BMS-986141	BMS-986141 0.8 mg QD for up to 28 days	BMS-986141 4.8 mg QD for up to 28 days
Measure Participants	0	0	0

6. Secondary Outcome

Title	Percentage of Participants Composite of Adjudicated Recurrent Ischemic Stroke, Myocardial Infarction, or Cardiovascular Death
Description	The percentage of treated participants with composite of adjudicated recurrent ischemic stroke, myocardial infarction, or cardiovascular death was reported by arm.
Time Frame	Day 90

Outcome Measure Data

Analysis Population Description

Insufficient data available to perform analysis due to study termination

Arm/Group Title	Placebo	BMS-986141 0.8 mg	BMS-986141 4.8 mg
Arm/Group Description	Matching placebo was taken once daily. Administration was exactly the same as for BMS-986141	BMS-986141 0.8 mg QD for up to 28 days	BMS-986141 4.8 mg QD for up to 28 days
Measure Participants	0	0	0

Adverse Events

Time Frame	From first dose until 30 days following last dose (assessed up to March 2017, approximately 6 months)
Arm/Group Title	Placebo		BMS-986141 0.8 mg		BMS-986141 4.8 mg
Arm/Group Description	Matching placebo was taken once daily. Administration was exactly the same as for BMS-986141		BMS-986141 0.8 mg QD for up to 28 days		BMS-986141 4.8 mg QD for up to 28 days
All Cause Mortality
	Placebo		BMS-986141 0.8 mg		BMS-986141 4.8 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/5 (0%)		0/7 (0%)
Serious Adverse Events
	Placebo		BMS-986141 0.8 mg		BMS-986141 4.8 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/5 (0%)		1/7 (14.3%)
Nervous system disorders
Encephalopathy	0/3 (0%)	0	0/5 (0%)	0	1/7 (14.3%)	1
Other (Not Including Serious) Adverse Events
	Placebo		BMS-986141 0.8 mg		BMS-986141 4.8 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		4/5 (80%)		3/7 (42.9%)
Gastrointestinal disorders
Constipation	0/3 (0%)	0	2/5 (40%)	2	0/7 (0%)	0
General disorders
Oedema Peripheral	0/3 (0%)	0	1/5 (20%)	1	0/7 (0%)	0
Infections and infestations
Tinea Pedis	0/3 (0%)	0	0/5 (0%)	0	1/7 (14.3%)	1
Sinusitis	0/3 (0%)	0	0/5 (0%)	0	1/7 (14.3%)	1
Viral Upper Respiratory Tract Infection	0/3 (0%)	0	0/5 (0%)	0	1/7 (14.3%)	1
Investigations
Blood Potassium Increased	0/3 (0%)	0	1/5 (20%)	1	0/7 (0%)	0
Metabolism and nutrition disorders
Hypokalaemia	0/3 (0%)	0	1/5 (20%)	1	0/7 (0%)	0
Musculoskeletal and connective tissue disorders
Muscle Spasms	0/3 (0%)	0	2/5 (40%)	2	0/7 (0%)	0
Renal and urinary disorders
Micturation Urgency	0/3 (0%)	0	1/5 (20%)	1	0/7 (0%)	0
Reproductive system and breast disorders
Vaginal Discharge	0/3 (0%)	0	0/5 (0%)	0	1/7 (14.3%)	1
Vulvovaginal Pruritis	0/3 (0%)	0	0/5 (0%)	0	1/7 (14.3%)	1
Respiratory, thoracic and mediastinal disorders
Cough	0/3 (0%)	0	1/5 (20%)	1	0/7 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.