A Blinded Study to Evaluate Effect on Atrial Fibrillation Burden in Patients With Paroxysmal Atrial Fibrillation
Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Terminated
CT.gov ID
NCT02156076
Collaborator
(none)
158
35
4
22.2
4.5
0.2
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the effect of BMS-919373 on atrial fibrillation (AF) through its effect on AF burden (AFB), or the percent of time in AF, in subjects with paroxysmal AF (pAF) when administered orally at a range of doses (2 mg once daily (QD), 5 mg QD, 12 mg QD following a 1-week period of loading doses of 3 mg QD, 8 mg QD and 20 mg QD, respectively) for a total of 4 weeks. It is hypothesized that treatment with BMS-919373 will reduce AF burden as compared to baseline relative to placebo.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
Primary Purpose: Protocol designed to assess, by the use of long term non-invasive beat-to-beat monitoring with the SEEQ Mobile Cardiac Telemetry (MCT) system, the effect of BMS-919373 on the percent change from baseline relative to placebo of atrial fibrillation burden in subjects with paroxysmal atrial fibrillation.
Study Design
Study Type:
Interventional
Actual Enrollment
:
158 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Other
Official Title:
A Randomized, Double-Blind, Placebo-Controlled Parallel Arm Study to Evaluate the Safety, Tolerability, and Effect on Atrial Fibrillation Burden of BMS-919373 in Patients With Paroxysmal Atrial Fibrillation
Actual Study Start Date
:
Jul 25, 2014
Actual Primary Completion Date
:
Jun 1, 2016
Actual Study Completion Date
:
Jun 1, 2016
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Arm A: Placebo (Matching with BMS-919373) Placebo (Matching with BMS-919373) 0 mg tablets orally once daily for approximately 28 Days |
Drug: Placebo (Matching with BMS-919373)
|
| Experimental: Arm B: BMS-919373 BMS-919373 3 mg tablets orally once daily for approximately 28 days |
Drug: BMS-919373
|
| Experimental: Arm C: BMS-919373 BMS-919373 5 mg tablets orally once daily for approximately 28 days |
Drug: BMS-919373
|
| Experimental: Arm D: BMS-919373 BMS-919373 12 mg tablets orally once daily for approximately 28 days |
Drug: BMS-919373
|
Outcome Measures
Primary Outcome Measures
- Percent Change From Baseline in Atrial Fibrillation Burden (AFB) as Assessed by SEEQ Mobile Cardiac Telemetry (MCT) System [Day 8 to Day 29]
AFB is defined as the percent of time spent in atrial fibrillation (AF). AFB will be assessed by use of long term non- invasive beat-to-beat monitoring with the SEEQ MCT system. This technology consists of a low-profile adhesive patch that has been approved for continuous use for up to 30 days. The patch is able to continuously record electrocardiographic signals and, in conjunction with a wirelessly connected portable cellular communications device, transmit these signals for real-time analysis, including atrial and ventricular arrhythmias and AFB.
Secondary Outcome Measures
- Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-related AEs and Death [Up to Day 50]
An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of investigational product, whether or not considered related to the investigational product. A SAE is any untoward medical occurrence that at any dose: results in death, is life-threatening (defined as an event in which the subject was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe), requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect.
- Maximum Observed Concentarion (Cmax) of BMS-919373 [Day 1 and Day 22: Predose 1, 2, and 4 hours postdose]
Cmax is defined as the maximum observed concentration of BMS-919373.
- Trough Observed Concentration (Cmin) of BMS-919373 [Day 8 (predose), Day 22 (predose, 1, 2, and 4 hours postdose), and Day 29 (24 hours after last dose of Day 28)]
Ctrough is defined as the minimum estimated plasma concentration at steady state.
- Oral Clearance (CL/F) of BMS-919373 [Day 8 (predose), Day 22 (predose, 1, 2, and 4 hours postdose), and Day 29 (24 hours after last dose of Day 28)]
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
- Central Volume of Distribution (Vc/F) of BMS-919373 [Day 8 (predose), Day 22 (predose, 1, 2, and 4 hours postdose), and Day 29 (24 hours after last dose of Day 28)]
Volume of distribution is defined as the theoretical volume in which the total amount of drug is uniformly distributed to produce the desired plasma concentration of a drug. Vc/F is a hypothetical volume into which a drug initially distributes upon administration.
- Absorption Rate Constant (Ka) of BMS-919373 [Day 8 (predose), Day 22 (predose, 1, 2, and 4 hours postdose), and Day 29 (24 hours after last dose of Day 28)]
Ka is the absorption rate constant.
- Average Concentration (Cavg) of BMS-919373 at Steady State [Day 8 (predose), Day 22 (predose, 1, 2, and 4 hours postdose), and Day 29 (24 hours after last dose of Day 28)]
Cavg is defines as the average concentration at steady state.
- Area Under the Concentration-time Curve (AUC) at Steady State of BMS-919373 [Day 8 (predose), Day 22 (predose, 1, 2, and 4 hours postdose), and Day 29 (24 hours after last dose of Day 28)]
AUC is defined as the area under the concentration-time curve at steady state.
- Time to First Atrial Fibrillation Recurrence (TTFR) (Symptomatic or Asymptomatic) [Day 8 to Day 29]
The TTFR is defined as the time to the first MCT-recorded AF episode after the first loading dose on Day 1. MCT will provide both "System-triggered" and "Patient-triggered" results and report them separately. "System-triggered" results will include both symptomatic and asymptomatic findings, while "Patient-triggered" results will be the symptomatic ones triggered to report by patients. The analysis will be done both for "System-triggered" and for "Patient-triggered" results.
- Total Number of Atrial Fibrillation Episodes [Day 8 to Day 29]
The total number AF episodes were derived from AF episode histogram data over the monitoring period.
- Average Duration of Atrial Fibrillation Per Episode [Day 8 to Day 29]
The average duration of AF per episode was calculated from the total time a participant in AF and the total number of AF episodes over the monitoring period.
Eligibility Criteria
Criteria
Ages Eligible for Study:
N/A
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:
-
Signed informed consent
-
Paroxysmal Atrial Fibrillation (pAF) with available documentation of AF and reporting symptoms within 6 months prior to screening
-
Able to tolerate withdrawal of antiarrhythmic therapy (rhythm control)
-
Echocardiographically measured left ventricular ejection fraction (LVEF) ≥40%,measured within 12 months of enrollment
-
Echocardiographically measured left atrial (LA) diameter ≤ 5.0 cm, measured within 12 months of enrollment
Exclusion Criteria:
-
Women of childbearing potential
-
AFB < 3% or > 70%, during both screening periods independently
-
Permanent or persistent Atrial Fibrillation
-
Cardioversion within 3 months of study drug administration
-
Stroke within 12 months of study drug administration
-
TIA within 12 months of study drug administration
-
Heart failure of NYHA class III or greater (symptoms of heart failure at rest or with minimal exertion)
-
Heart failure of NYHA class II (symptoms of heart failure with routine levels of exertion)with ejection fraction <40% as measured by echocardiography at any time within 12 months of study enrollment (i.e. additional ejection fraction measurements ≥ 40% over this period will not counter this exclusion)
-
Valvular heart disease (including any valvular insufficiency or stenosis greater than"mild")
-
Ablation within 3 months of study enrollment
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cardiology Consultants Of Orange County Med. Group Inc | Anaheim | California | United States | 92801 |
| 2 | Oracle Clinical Research, Inc. | Anaheim | California | United States | 92801 |
| 3 | Wcct Global, Llc | Costa Mesa | California | United States | 92626 |
| 4 | Long Beach Va Medical Center | Long Beach | California | United States | 90822 |
| 5 | Spectrum Clinical Research | Moreno Valley | California | United States | 92553 |
| 6 | Chase Medical Research, Llc | Waterbury | Connecticut | United States | 06708 |
| 7 | All Medical Research, Llc | Cooper City | Florida | United States | 33024 |
| 8 | The Cardiac And Vascular Institute Research Foundation, Llc | Gainesville | Florida | United States | 32605 |
| 9 | Acrc Cardiology | Lake Worth | Florida | United States | 33462 |
| 10 | The Heart Institute At Largo | Largo | Florida | United States | 33770 |
| 11 | Columbus Regional Research Institute | Columbus | Georgia | United States | 31904 |
| 12 | Community Clinical Research Center | Anderson | Indiana | United States | 46011 |
| 13 | Midwest Heart And Vascular Specialists, Llc. | Overland Park | Kansas | United States | 66209 |
| 14 | Cambridge Medical Trials | Alexandria | Louisiana | United States | 71301 |
| 15 | Castlerock Clinical Research Consultants, Llc | Tulsa | Oklahoma | United States | 74136 |
| 16 | Capital Area Research, Llc | Camp Hill | Pennsylvania | United States | 17011 |
| 17 | Tennessee Center For Clinical Trials | Tullahoma | Tennessee | United States | 37388 |
| 18 | Local Institution | Austin | Texas | United States | 78705 |
| 19 | Local Institution | Austin | Texas | United States | |
| 20 | Utah Cardiology P.C | Layton | Utah | United States | 84041 |
| 21 | Local Institution | Edmonton | Alberta | Canada | T6G 2B7 |
| 22 | Fraser Clinical Trials Inc. | New Westminster | British Columbia | Canada | V3L 3W4 |
| 23 | Local Institution | Cambridge | Ontario | Canada | N1R 7R1 |
| 24 | Dr. Andy S.C. Lam Medicine Professional | Grimsby | Ontario | Canada | L3M 1P3 |
| 25 | Stroke Prevention & Artherosclerosis Research Centre | London | Ontario | Canada | N6G 2V4 |
| 26 | Local Institution | Newmarket | Ontario | Canada | |
| 27 | Local Institution | Oshawa | Ontario | Canada | L1J 2J9 |
| 28 | King Street Cardiology | Oshawa | Ontario | Canada | L1J 2K1 |
| 29 | Local Institution | Toronto | Ontario | Canada | M3M 3E5 |
| 30 | Local Institution | Waterloo | Ontario | Canada | N2T 0C1 |
| 31 | Viacar Recherche Clinique | Greenfield Park | Quebec | Canada | J4V 2G8 |
| 32 | Local Institution | Montreal | Quebec | Canada | H1T 1C8 |
| 33 | Local Institution | Montreal | Quebec | Canada | H2W 1T8 |
| 34 | Csss Du Sud De Lanaudiere-Hopital Pierre-Le Gardeur | Terrebonne | Quebec | Canada | J6V 2H2 |
| 35 | Local Institution | Quebec | Canada | G1V 4G5 |
Sponsors and Collaborators
- Bristol-Myers Squibb
Investigators
- Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT02156076
Other Study ID Numbers:
- CV205-005
First Posted:
Jun 5, 2014
Last Update Posted:
Jul 31, 2019
Last Verified:
Jul 1, 2019
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Total 158 participants were enrolled out of which 26 participants were randomized and treated. |
| Arm/Group Title | BMS-919373 3/2 mg | BMS-919373 8/5 mg | BMS-919373 20/12 mg | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Participants received loading dose of BMS-919373 3 milligram (mg) as oral tablets (each tablet of 1 mg*3) once daily (QD) for one week followed by maintenance dose of BMS-919373 2 mg as oral tablets (each tablet of 1 mg*2) QD for 3 weeks. | Participants received loading dose of BMS-919373 8 mg as oral tablets (each tablet of 1 mg*3 + 5 mg*1) QD for one week followed by maintenance dose of BMS-919373 5 mg as oral tablets (each tablet of 5 mg*1) QD for 3 weeks. | Participants received loading dose of BMS-919373 20 mg as oral tablets (each tablet of 5 mg*4) QD for one week followed by maintenance dose of BMS-919373 12 mg as oral tablets (each tablet of 5 mg*2 + 1 mg*2) QD for 3 weeks. | Participants received placebo matching with BMS-919373 0 mg tablets (4 tablets) orally QD for 28 Days. |
| Period Title: Treatment Period | ||||
| STARTED | 7 | 7 | 6 | 6 |
| COMPLETED | 7 | 5 | 4 | 4 |
| NOT COMPLETED | 0 | 2 | 2 | 2 |
| Period Title: Treatment Period | ||||
| STARTED | 7 | 5 | 4 | 4 |
| COMPLETED | 6 | 5 | 4 | 4 |
| NOT COMPLETED | 1 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | BMS-919373 3/2 mg | BMS-919373 8/5 mg | BMS-919373 20/12 mg | Placebo | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received loading dose of BMS-919373 3 milligram (mg) as oral tablets (each tablet of 1 mg*3) once daily (QD) for one week followed by maintenance dose of BMS-919373 2 mg as oral tablets (each tablet of 1 mg*2) QD for 3 weeks. | Participants received loading dose of BMS-919373 8 mg as oral tablets (each tablet of 1 mg*3 + 5 mg*1) QD for one week followed by maintenance dose of BMS-919373 5 mg as oral tablets (each tablet of 5 mg*1) QD for 3 weeks. | Participants received loading dose of BMS-919373 20 mg as oral tablets (each tablet of 5 mg*4) QD for one week followed by maintenance dose of BMS-919373 12 mg as oral tablets (each tablet of 5 mg*2 + 1 mg*2) QD for 3 weeks. | Participants received placebo matching with BMS-919373 0 mg tablets (4 tablets) orally QD for 28 Days. | Total of all reporting groups |
| Overall Participants | 7 | 7 | 6 | 6 | 26 |
| Age (Years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [Years] |
70.0
(5.83)
|
61.0
(8.23)
|
65.7
(10.05)
|
65.0
(10.77)
|
65.4
(8.90)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
1
14.3%
|
3
42.9%
|
1
16.7%
|
2
33.3%
|
7
26.9%
|
| Male |
6
85.7%
|
4
57.1%
|
5
83.3%
|
4
66.7%
|
19
73.1%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||
| Hispanic or Latino |
0
0%
|
1
14.3%
|
0
0%
|
2
33.3%
|
3
11.5%
|
| Not Hispanic or Latino |
5
71.4%
|
5
71.4%
|
3
50%
|
3
50%
|
16
61.5%
|
| Unknown or Not Reported |
2
28.6%
|
1
14.3%
|
3
50%
|
1
16.7%
|
7
26.9%
|
| Race (NIH/OMB) (Count of Participants) | |||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
1
3.8%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
2
33.3%
|
0
0%
|
2
7.7%
|
| White |
7
100%
|
7
100%
|
4
66.7%
|
5
83.3%
|
23
88.5%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Percent Change From Baseline in Atrial Fibrillation Burden (AFB) as Assessed by SEEQ Mobile Cardiac Telemetry (MCT) System |
|---|---|
| Description | AFB is defined as the percent of time spent in atrial fibrillation (AF). AFB will be assessed by use of long term non- invasive beat-to-beat monitoring with the SEEQ MCT system. This technology consists of a low-profile adhesive patch that has been approved for continuous use for up to 30 days. The patch is able to continuously record electrocardiographic signals and, in conjunction with a wirelessly connected portable cellular communications device, transmit these signals for real-time analysis, including atrial and ventricular arrhythmias and AFB. |
| Time Frame | Day 8 to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was not collected for any participants due to termination of the study |
| Arm/Group Title | BMS-919373 3/2 mg | BMS-919373 8/5 mg | BMS-919373 20/12 mg | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Participants received loading dose of BMS-919373 3 milligram (mg) as oral tablets (each tablet of 1 mg*3) once daily (QD) for one week followed by maintenance dose of BMS-919373 2 mg as oral tablets (each tablet of 1 mg*2) QD for 3 weeks. | Participants received loading dose of BMS-919373 8 mg as oral tablets (each tablet of 1 mg*3 + 5 mg*1) QD for one week followed by maintenance dose of BMS-919373 5 mg as oral tablets (each tablet of 5 mg*1) QD for 3 weeks. | Participants received loading dose of BMS-919373 20 mg as oral tablets (each tablet of 5 mg*4) QD for one week followed by maintenance dose of BMS-919373 12 mg as oral tablets (each tablet of 5 mg*2 + 1 mg*2) QD for 3 weeks. | Participants received placebo matching with BMS-919373 0 mg tablets (4 tablets) orally QD for 28 Days. |
| Measure Participants | 0 | 0 | 0 | 0 |
| Title | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-related AEs and Death |
|---|---|
| Description | An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of investigational product, whether or not considered related to the investigational product. A SAE is any untoward medical occurrence that at any dose: results in death, is life-threatening (defined as an event in which the subject was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe), requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect. |
| Time Frame | Up to Day 50 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants included all the participants who have received at least one dose of study treatment. |
| Arm/Group Title | BMS-919373 3/2 mg | BMS-919373 8/5 mg | BMS-919373 20/12 mg | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Participants received loading dose of BMS-919373 3 milligram (mg) as oral tablets (each tablet of 1 mg*3) once daily (QD) for one week followed by maintenance dose of BMS-919373 2 mg as oral tablets (each tablet of 1 mg*2) QD for 3 weeks. | Participants received loading dose of BMS-919373 8 mg as oral tablets (each tablet of 1 mg*3 + 5 mg*1) QD for one week followed by maintenance dose of BMS-919373 5 mg as oral tablets (each tablet of 5 mg*1) QD for 3 weeks. | Participants received loading dose of BMS-919373 20 mg as oral tablets (each tablet of 5 mg*4) QD for one week followed by maintenance dose of BMS-919373 12 mg as oral tablets (each tablet of 5 mg*2 + 1 mg*2) QD for 3 weeks. | Participants received placebo matching with BMS-919373 0 mg tablets (4 tablets) orally QD for 28 Days. |
| Measure Participants | 7 | 7 | 6 | 6 |
| AEs |
4
57.1%
|
4
57.1%
|
3
50%
|
4
66.7%
|
| SAEs |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Treatment-related AEs |
0
0%
|
3
42.9%
|
0
0%
|
0
0%
|
| Death |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Maximum Observed Concentarion (Cmax) of BMS-919373 |
|---|---|
| Description | Cmax is defined as the maximum observed concentration of BMS-919373. |
| Time Frame | Day 1 and Day 22: Predose 1, 2, and 4 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was not collected for any participants due to termination of the study |
| Arm/Group Title | BMS-919373 3/2 mg | BMS-919373 8/5 mg | BMS-919373 20/12 mg | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Participants received loading dose of BMS-919373 3 milligram (mg) as oral tablets (each tablet of 1 mg*3) once daily (QD) for one week followed by maintenance dose of BMS-919373 2 mg as oral tablets (each tablet of 1 mg*2) QD for 3 weeks. | Participants received loading dose of BMS-919373 8 mg as oral tablets (each tablet of 1 mg*3 + 5 mg*1) QD for one week followed by maintenance dose of BMS-919373 5 mg as oral tablets (each tablet of 5 mg*1) QD for 3 weeks. | Participants received loading dose of BMS-919373 20 mg as oral tablets (each tablet of 5 mg*4) QD for one week followed by maintenance dose of BMS-919373 12 mg as oral tablets (each tablet of 5 mg*2 + 1 mg*2) QD for 3 weeks. | Participants received placebo matching with BMS-919373 0 mg tablets (4 tablets) orally QD for 28 Days. |
| Measure Participants | 0 | 0 | 0 | 0 |
| Title | Trough Observed Concentration (Cmin) of BMS-919373 |
|---|---|
| Description | Ctrough is defined as the minimum estimated plasma concentration at steady state. |
| Time Frame | Day 8 (predose), Day 22 (predose, 1, 2, and 4 hours postdose), and Day 29 (24 hours after last dose of Day 28) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was not collected for any participants due to termination of the study |
| Arm/Group Title | BMS-919373 3/2 mg | BMS-919373 8/5 mg | BMS-919373 20/12 mg | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Participants received loading dose of BMS-919373 3 milligram (mg) as oral tablets (each tablet of 1 mg*3) once daily (QD) for one week followed by maintenance dose of BMS-919373 2 mg as oral tablets (each tablet of 1 mg*2) QD for 3 weeks. | Participants received loading dose of BMS-919373 8 mg as oral tablets (each tablet of 1 mg*3 + 5 mg*1) QD for one week followed by maintenance dose of BMS-919373 5 mg as oral tablets (each tablet of 5 mg*1) QD for 3 weeks. | Participants received loading dose of BMS-919373 20 mg as oral tablets (each tablet of 5 mg*4) QD for one week followed by maintenance dose of BMS-919373 12 mg as oral tablets (each tablet of 5 mg*2 + 1 mg*2) QD for 3 weeks. | Participants received placebo matching with BMS-919373 0 mg tablets (4 tablets) orally QD for 28 Days. |
| Measure Participants | 0 | 0 | 0 | 0 |
| Title | Oral Clearance (CL/F) of BMS-919373 |
|---|---|
| Description | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. |
| Time Frame | Day 8 (predose), Day 22 (predose, 1, 2, and 4 hours postdose), and Day 29 (24 hours after last dose of Day 28) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was not collected for any participants due to termination of the study |
| Arm/Group Title | BMS-919373 3/2 mg | BMS-919373 8/5 mg | BMS-919373 20/12 mg | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Participants received loading dose of BMS-919373 3 milligram (mg) as oral tablets (each tablet of 1 mg*3) once daily (QD) for one week followed by maintenance dose of BMS-919373 2 mg as oral tablets (each tablet of 1 mg*2) QD for 3 weeks. | Participants received loading dose of BMS-919373 8 mg as oral tablets (each tablet of 1 mg*3 + 5 mg*1) QD for one week followed by maintenance dose of BMS-919373 5 mg as oral tablets (each tablet of 5 mg*1) QD for 3 weeks. | Participants received loading dose of BMS-919373 20 mg as oral tablets (each tablet of 5 mg*4) QD for one week followed by maintenance dose of BMS-919373 12 mg as oral tablets (each tablet of 5 mg*2 + 1 mg*2) QD for 3 weeks. | Participants received placebo matching with BMS-919373 0 mg tablets (4 tablets) orally QD for 28 Days. |
| Measure Participants | 0 | 0 | 0 | 0 |
| Title | Central Volume of Distribution (Vc/F) of BMS-919373 |
|---|---|
| Description | Volume of distribution is defined as the theoretical volume in which the total amount of drug is uniformly distributed to produce the desired plasma concentration of a drug. Vc/F is a hypothetical volume into which a drug initially distributes upon administration. |
| Time Frame | Day 8 (predose), Day 22 (predose, 1, 2, and 4 hours postdose), and Day 29 (24 hours after last dose of Day 28) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was not collected for any participants due to termination of the study |
| Arm/Group Title | BMS-919373 3/2 mg | BMS-919373 8/5 mg | BMS-919373 20/12 mg | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Participants received loading dose of BMS-919373 3 milligram (mg) as oral tablets (each tablet of 1 mg*3) once daily (QD) for one week followed by maintenance dose of BMS-919373 2 mg as oral tablets (each tablet of 1 mg*2) QD for 3 weeks. | Participants received loading dose of BMS-919373 8 mg as oral tablets (each tablet of 1 mg*3 + 5 mg*1) QD for one week followed by maintenance dose of BMS-919373 5 mg as oral tablets (each tablet of 5 mg*1) QD for 3 weeks. | Participants received loading dose of BMS-919373 20 mg as oral tablets (each tablet of 5 mg*4) QD for one week followed by maintenance dose of BMS-919373 12 mg as oral tablets (each tablet of 5 mg*2 + 1 mg*2) QD for 3 weeks. | Participants received placebo matching with BMS-919373 0 mg tablets (4 tablets) orally QD for 28 Days. |
| Measure Participants | 0 | 0 | 0 | 0 |
| Title | Absorption Rate Constant (Ka) of BMS-919373 |
|---|---|
| Description | Ka is the absorption rate constant. |
| Time Frame | Day 8 (predose), Day 22 (predose, 1, 2, and 4 hours postdose), and Day 29 (24 hours after last dose of Day 28) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was not collected for any participants due to termination of the study |
| Arm/Group Title | BMS-919373 3/2 mg | BMS-919373 8/5 mg | BMS-919373 20/12 mg | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Participants received loading dose of BMS-919373 3 milligram (mg) as oral tablets (each tablet of 1 mg*3) once daily (QD) for one week followed by maintenance dose of BMS-919373 2 mg as oral tablets (each tablet of 1 mg*2) QD for 3 weeks. | Participants received loading dose of BMS-919373 8 mg as oral tablets (each tablet of 1 mg*3 + 5 mg*1) QD for one week followed by maintenance dose of BMS-919373 5 mg as oral tablets (each tablet of 5 mg*1) QD for 3 weeks. | Participants received loading dose of BMS-919373 20 mg as oral tablets (each tablet of 5 mg*4) QD for one week followed by maintenance dose of BMS-919373 12 mg as oral tablets (each tablet of 5 mg*2 + 1 mg*2) QD for 3 weeks. | Participants received placebo matching with BMS-919373 0 mg tablets (4 tablets) orally QD for 28 Days. |
| Measure Participants | 0 | 0 | 0 | 0 |
| Title | Average Concentration (Cavg) of BMS-919373 at Steady State |
|---|---|
| Description | Cavg is defines as the average concentration at steady state. |
| Time Frame | Day 8 (predose), Day 22 (predose, 1, 2, and 4 hours postdose), and Day 29 (24 hours after last dose of Day 28) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was not collected for any participants due to termination of the study |
| Arm/Group Title | BMS-919373 3/2 mg | BMS-919373 8/5 mg | BMS-919373 20/12 mg | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Participants received loading dose of BMS-919373 3 milligram (mg) as oral tablets (each tablet of 1 mg*3) once daily (QD) for one week followed by maintenance dose of BMS-919373 2 mg as oral tablets (each tablet of 1 mg*2) QD for 3 weeks. | Participants received loading dose of BMS-919373 8 mg as oral tablets (each tablet of 1 mg*3 + 5 mg*1) QD for one week followed by maintenance dose of BMS-919373 5 mg as oral tablets (each tablet of 5 mg*1) QD for 3 weeks. | Participants received loading dose of BMS-919373 20 mg as oral tablets (each tablet of 5 mg*4) QD for one week followed by maintenance dose of BMS-919373 12 mg as oral tablets (each tablet of 5 mg*2 + 1 mg*2) QD for 3 weeks. | Participants received placebo matching with BMS-919373 0 mg tablets (4 tablets) orally QD for 28 Days. |
| Measure Participants | 0 | 0 | 0 | 0 |
| Title | Area Under the Concentration-time Curve (AUC) at Steady State of BMS-919373 |
|---|---|
| Description | AUC is defined as the area under the concentration-time curve at steady state. |
| Time Frame | Day 8 (predose), Day 22 (predose, 1, 2, and 4 hours postdose), and Day 29 (24 hours after last dose of Day 28) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was not collected for any participants due to termination of the study |
| Arm/Group Title | BMS-919373 3/2 mg | BMS-919373 8/5 mg | BMS-919373 20/12 mg | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Participants received loading dose of BMS-919373 3 milligram (mg) as oral tablets (each tablet of 1 mg*3) once daily (QD) for one week followed by maintenance dose of BMS-919373 2 mg as oral tablets (each tablet of 1 mg*2) QD for 3 weeks. | Participants received loading dose of BMS-919373 8 mg as oral tablets (each tablet of 1 mg*3 + 5 mg*1) QD for one week followed by maintenance dose of BMS-919373 5 mg as oral tablets (each tablet of 5 mg*1) QD for 3 weeks. | Participants received loading dose of BMS-919373 20 mg as oral tablets (each tablet of 5 mg*4) QD for one week followed by maintenance dose of BMS-919373 12 mg as oral tablets (each tablet of 5 mg*2 + 1 mg*2) QD for 3 weeks. | Participants received placebo matching with BMS-919373 0 mg tablets (4 tablets) orally QD for 28 Days. |
| Measure Participants | 0 | 0 | 0 | 0 |
| Title | Time to First Atrial Fibrillation Recurrence (TTFR) (Symptomatic or Asymptomatic) |
|---|---|
| Description | The TTFR is defined as the time to the first MCT-recorded AF episode after the first loading dose on Day 1. MCT will provide both "System-triggered" and "Patient-triggered" results and report them separately. "System-triggered" results will include both symptomatic and asymptomatic findings, while "Patient-triggered" results will be the symptomatic ones triggered to report by patients. The analysis will be done both for "System-triggered" and for "Patient-triggered" results. |
| Time Frame | Day 8 to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was not collected for any participants due to termination of the study |
| Arm/Group Title | BMS-919373 3/2 mg | BMS-919373 8/5 mg | BMS-919373 20/12 mg | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Participants received loading dose of BMS-919373 3 milligram (mg) as oral tablets (each tablet of 1 mg*3) once daily (QD) for one week followed by maintenance dose of BMS-919373 2 mg as oral tablets (each tablet of 1 mg*2) QD for 3 weeks. | Participants received loading dose of BMS-919373 8 mg as oral tablets (each tablet of 1 mg*3 + 5 mg*1) QD for one week followed by maintenance dose of BMS-919373 5 mg as oral tablets (each tablet of 5 mg*1) QD for 3 weeks. | Participants received loading dose of BMS-919373 20 mg as oral tablets (each tablet of 5 mg*4) QD for one week followed by maintenance dose of BMS-919373 12 mg as oral tablets (each tablet of 5 mg*2 + 1 mg*2) QD for 3 weeks. | Participants received placebo matching with BMS-919373 0 mg tablets (4 tablets) orally QD for 28 Days. |
| Measure Participants | 0 | 0 | 0 | 0 |
| Title | Total Number of Atrial Fibrillation Episodes |
|---|---|
| Description | The total number AF episodes were derived from AF episode histogram data over the monitoring period. |
| Time Frame | Day 8 to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was not collected for any participants due to termination of the study |
| Arm/Group Title | BMS-919373 3/2 mg | BMS-919373 8/5 mg | BMS-919373 20/12 mg | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Participants received loading dose of BMS-919373 3 milligram (mg) as oral tablets (each tablet of 1 mg*3) once daily (QD) for one week followed by maintenance dose of BMS-919373 2 mg as oral tablets (each tablet of 1 mg*2) QD for 3 weeks. | Participants received loading dose of BMS-919373 8 mg as oral tablets (each tablet of 1 mg*3 + 5 mg*1) QD for one week followed by maintenance dose of BMS-919373 5 mg as oral tablets (each tablet of 5 mg*1) QD for 3 weeks. | Participants received loading dose of BMS-919373 20 mg as oral tablets (each tablet of 5 mg*4) QD for one week followed by maintenance dose of BMS-919373 12 mg as oral tablets (each tablet of 5 mg*2 + 1 mg*2) QD for 3 weeks. | Participants received placebo matching with BMS-919373 0 mg tablets (4 tablets) orally QD for 28 Days. |
| Measure Participants | 0 | 0 | 0 | 0 |
| Title | Average Duration of Atrial Fibrillation Per Episode |
|---|---|
| Description | The average duration of AF per episode was calculated from the total time a participant in AF and the total number of AF episodes over the monitoring period. |
| Time Frame | Day 8 to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was not collected for any participants due to termination of the study |
| Arm/Group Title | BMS-919373 3/2 mg | BMS-919373 8/5 mg | BMS-919373 20/12 mg | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Participants received loading dose of BMS-919373 3 milligram (mg) as oral tablets (each tablet of 1 mg*3) once daily (QD) for one week followed by maintenance dose of BMS-919373 2 mg as oral tablets (each tablet of 1 mg*2) QD for 3 weeks. | Participants received loading dose of BMS-919373 8 mg as oral tablets (each tablet of 1 mg*3 + 5 mg*1) QD for one week followed by maintenance dose of BMS-919373 5 mg as oral tablets (each tablet of 5 mg*1) QD for 3 weeks. | Participants received loading dose of BMS-919373 20 mg as oral tablets (each tablet of 5 mg*4) QD for one week followed by maintenance dose of BMS-919373 12 mg as oral tablets (each tablet of 5 mg*2 + 1 mg*2) QD for 3 weeks. | Participants received placebo matching with BMS-919373 0 mg tablets (4 tablets) orally QD for 28 Days. |
| Measure Participants | 0 | 0 | 0 | 0 |
Adverse Events
| Time Frame | Approximately 50 days | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | All treated participants included all the participants who have received at least one dose of study treatment. | |||||||
| Arm/Group Title | Placebo | BMS-919373 3/2 mg | BMS-919373 8/5 mg | BMS-919373 20/12 mg | ||||
| Arm/Group Description | Participants received placebo matching with BMS-919373 0 mg tablets (4 tablets) orally QD for 28 Days. | Participants received loading dose of BMS-919373 3 milligram (mg) as oral tablets (each tablet of 1 mg*3) once daily (QD) for one week followed by maintenance dose of BMS-919373 2 mg as oral tablets (each tablet of 1 mg*2) QD for 3 weeks. | Participants received loading dose of BMS-919373 8 mg as oral tablets (each tablet of 1 mg*3 + 5 mg*1) QD for one week followed by maintenance dose of BMS-919373 5 mg as oral tablets (each tablet of 5 mg*1) QD for 3 weeks. | Participants received loading dose of BMS-919373 20 mg as oral tablets (each tablet of 5 mg*4) QD for one week followed by maintenance dose of BMS-919373 12 mg as oral tablets (each tablet of 5 mg*2 + 1 mg*2) QD for 3 weeks. | ||||
All Cause Mortality |
||||||||
| Placebo | BMS-919373 3/2 mg | BMS-919373 8/5 mg | BMS-919373 20/12 mg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/6 (0%) | 0/7 (0%) | 0/7 (0%) | 0/6 (0%) | ||||
Serious Adverse Events |
||||||||
| Placebo | BMS-919373 3/2 mg | BMS-919373 8/5 mg | BMS-919373 20/12 mg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/6 (0%) | 0/7 (0%) | 0/7 (0%) | 0/6 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Placebo | BMS-919373 3/2 mg | BMS-919373 8/5 mg | BMS-919373 20/12 mg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/6 (66.7%) | 4/7 (57.1%) | 4/7 (57.1%) | 3/6 (50%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Eosinophilia | 0/6 (0%) | 0/7 (0%) | 1/7 (14.3%) | 0/6 (0%) | ||||
| Eye disorders | ||||||||
| Vision Blurred | 1/6 (16.7%) | 0/7 (0%) | 0/7 (0%) | 0/6 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal Distension | 0/6 (0%) | 0/7 (0%) | 1/7 (14.3%) | 0/6 (0%) | ||||
| Diarrhoea | 0/6 (0%) | 1/7 (14.3%) | 0/7 (0%) | 0/6 (0%) | ||||
| Nausea | 0/6 (0%) | 0/7 (0%) | 1/7 (14.3%) | 0/6 (0%) | ||||
| Oral Pain | 1/6 (16.7%) | 0/7 (0%) | 0/7 (0%) | 0/6 (0%) | ||||
| General disorders | ||||||||
| Energy Increased | 0/6 (0%) | 0/7 (0%) | 1/7 (14.3%) | 0/6 (0%) | ||||
| Fatigue | 0/6 (0%) | 1/7 (14.3%) | 0/7 (0%) | 0/6 (0%) | ||||
| Medical Device Site Dermatitis | 0/6 (0%) | 0/7 (0%) | 1/7 (14.3%) | 0/6 (0%) | ||||
| Oedema Peripheral | 0/6 (0%) | 0/7 (0%) | 1/7 (14.3%) | 0/6 (0%) | ||||
| Infections and infestations | ||||||||
| Skin Infection | 0/6 (0%) | 0/7 (0%) | 1/7 (14.3%) | 0/6 (0%) | ||||
| Staphylococcal Infection | 0/6 (0%) | 0/7 (0%) | 1/7 (14.3%) | 0/6 (0%) | ||||
| Urinary Tract Infection | 0/6 (0%) | 0/7 (0%) | 1/7 (14.3%) | 0/6 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Decreased Appetite | 0/6 (0%) | 0/7 (0%) | 1/7 (14.3%) | 0/6 (0%) | ||||
| Nervous system disorders | ||||||||
| Dizziness | 0/6 (0%) | 2/7 (28.6%) | 0/7 (0%) | 0/6 (0%) | ||||
| Head Discomfort | 0/6 (0%) | 0/7 (0%) | 1/7 (14.3%) | 0/6 (0%) | ||||
| Tremor | 0/6 (0%) | 0/7 (0%) | 0/7 (0%) | 1/6 (16.7%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Choking Sensation | 0/6 (0%) | 1/7 (14.3%) | 0/7 (0%) | 0/6 (0%) | ||||
| Dyspnoe | 0/6 (0%) | 1/7 (14.3%) | 0/7 (0%) | 0/6 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Dermatitis Contact | 1/6 (16.7%) | 0/7 (0%) | 0/7 (0%) | 1/6 (16.7%) | ||||
| Rash | 0/6 (0%) | 0/7 (0%) | 1/7 (14.3%) | 0/6 (0%) | ||||
| Skin Irritation | 1/6 (16.7%) | 0/7 (0%) | 0/7 (0%) | 0/6 (0%) | ||||
| Swelling Face | 0/6 (0%) | 1/7 (14.3%) | 0/7 (0%) | 0/6 (0%) | ||||
| Vascular disorders | ||||||||
| Thrombosis | 0/6 (0%) | 0/7 (0%) | 0/7 (0%) | 1/6 (16.7%) | ||||
Limitations/Caveats
Sponsor decided to terminate development of BMS-919373 for business reasons unrelated to safety, due to which data was not analyzed for maximum outcome measures.
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.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Bristol-Myers Squibb |
| Phone | |
| Clinical.Trials@bms.com |
Responsible Party:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT02156076
Other Study ID Numbers:
- CV205-005
First Posted:
Jun 5, 2014
Last Update Posted:
Jul 31, 2019
Last Verified:
Jul 1, 2019