A Blinded Study to Evaluate Effect on Atrial Fibrillation Burden in Patients With Paroxysmal Atrial Fibrillation

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

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.

Study Overview

• Status: Terminated
• Conditions: Paroxysmal Atrial Fibrillation
• Intervention / Treatment: Drug: BMS-919373; Drug: Placebo (Matching with BMS-919373)

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 Type: Interventional
• Enrollment (Actual): 158
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V 4G5
    • Local Institution
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • Local Institution
  • British Columbia
    • New Westminster, British Columbia, Canada, V3L 3W4
      • Fraser Clinical Trials Inc.
  • Ontario
    • Cambridge, Ontario, Canada, N1R 7R1
      • Local Institution
    • Grimsby, Ontario, Canada, L3M 1P3
      • Dr. Andy S.C. Lam Medicine Professional
    • London, Ontario, Canada, N6G 2V4
      • Stroke Prevention & Artherosclerosis Research Centre
    • Newmarket, Ontario, Canada
      • Local Institution
    • Oshawa, Ontario, Canada, L1J 2J9
      • Local Institution
    • Oshawa, Ontario, Canada, L1J 2K1
      • King Street Cardiology
    • Toronto, Ontario, Canada, M3M 3E5
      • Local Institution
    • Waterloo, Ontario, Canada, N2T 0C1
      • Local Institution
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2G8
      • Viacar Recherche Clinique
    • Montreal, Quebec, Canada, H1T 1C8
      • Local Institution
    • Montreal, Quebec, Canada, H2W 1T8
      • Local Institution
    • Terrebonne, Quebec, Canada, J6V 2H2
      • Csss Du Sud De Lanaudiere-Hopital Pierre-Le Gardeur
• United States
  • California
    • Anaheim, California, United States, 92801
      • Oracle Clinical Research, Inc.
    • Anaheim, California, United States, 92801
      • Cardiology Consultants Of Orange County Med. Group Inc
    • Costa Mesa, California, United States, 92626
      • WCCT Global, LLC
    • Long Beach, California, United States, 90822
      • Long Beach VA Medical Center
    • Moreno Valley, California, United States, 92553
      • Spectrum Clinical Research
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Chase Medical Research, LLC
  • Florida
    • Cooper City, Florida, United States, 33024
      • ALL Medical Research, LLC
    • Gainesville, Florida, United States, 32605
      • The Cardiac And Vascular Institute Research Foundation, Llc
    • Lake Worth, Florida, United States, 33462
      • Acrc Cardiology
    • Largo, Florida, United States, 33770
      • The Heart Institute at Largo
  • Georgia
    • Columbus, Georgia, United States, 31904
      • Columbus Regional Research Institute
  • Indiana
    • Anderson, Indiana, United States, 46011
      • Community Clinical Research Center
  • Kansas
    • Overland Park, Kansas, United States, 66209
      • Midwest Heart And Vascular Specialists, Llc.
  • Louisiana
    • Alexandria, Louisiana, United States, 71301
      • Cambridge Medical Trials
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Castlerock Clinical Research Consultants, Llc
  • Pennsylvania
    • Camp Hill, Pennsylvania, United States, 17011
      • Capital Area Research, LLC
  • Tennessee
    • Tullahoma, Tennessee, United States, 37388
      • Tennessee Center for Clinical Trials
  • Texas
    • Austin, Texas, United States
      • Local Institution
    • Austin, Texas, United States, 78705
      • Local Institution
  • Utah
    • Layton, Utah, United States, 84041
      • Utah Cardiology P.C

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Atrial Fibrillation Burden (AFB) as Assessed by SEEQ Mobile Cardiac Telemetry (MCT) System	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.	Day 8 to Day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-related AEs and Death	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.	Up to Day 50
Maximum Observed Concentarion (Cmax) of BMS-919373	Cmax is defined as the maximum observed concentration of BMS-919373.	Day 1 and Day 22: Predose 1, 2, and 4 hours postdose
Trough Observed Concentration (Cmin) of BMS-919373	Ctrough is defined as the minimum estimated plasma concentration 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)
Oral Clearance (CL/F) of BMS-919373	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.	Day 8 (predose), Day 22 (predose, 1, 2, and 4 hours postdose), and Day 29 (24 hours after last dose of Day 28)
Central Volume of Distribution (Vc/F) of BMS-919373	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.	Day 8 (predose), Day 22 (predose, 1, 2, and 4 hours postdose), and Day 29 (24 hours after last dose of Day 28)
Absorption Rate Constant (Ka) of BMS-919373	Ka is the absorption rate constant.	Day 8 (predose), Day 22 (predose, 1, 2, and 4 hours postdose), and Day 29 (24 hours after last dose of Day 28)
Average Concentration (Cavg) of BMS-919373 at Steady State	Cavg is defines as the average concentration 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)
Area Under the Concentration-time Curve (AUC) at Steady State of BMS-919373	AUC is defined as the area under the concentration-time curve 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)
Time to First Atrial Fibrillation Recurrence (TTFR) (Symptomatic or Asymptomatic)	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.	Day 8 to Day 29
Total Number of Atrial Fibrillation Episodes	The total number AF episodes were derived from AF episode histogram data over the monitoring period.	Day 8 to Day 29
Average Duration of Atrial Fibrillation Per Episode	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.	Day 8 to Day 29

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS clinical trial educational resource
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): July 25, 2014
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: May 12, 2014
• First Submitted That Met QC Criteria: June 3, 2014
• First Posted (Estimate): June 5, 2014

Study Record Updates

• Last Update Posted (Actual): July 31, 2019
• Last Update Submitted That Met QC Criteria: July 29, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: CV205-005