A Blinded Study to Evaluate Effect on Atrial Fibrillation Burden in Patients With Paroxysmal Atrial Fibrillation
- Conditions
- Paroxysmal Atrial Fibrillation
- Interventions
- Drug: Placebo (Matching with BMS-919373)
- Registration Number
- NCT02156076
- Lead Sponsor
- Bristol-Myers Squibb
- 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.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 158
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: Placebo (Matching with BMS-919373) Placebo (Matching with BMS-919373) Placebo (Matching with BMS-919373) 0 mg tablets orally once daily for approximately 28 Days Arm C: BMS-919373 BMS-919373 BMS-919373 5 mg tablets orally once daily for approximately 28 days Arm B: BMS-919373 BMS-919373 BMS-919373 3 mg tablets orally once daily for approximately 28 days Arm D: BMS-919373 BMS-919373 BMS-919373 12 mg tablets orally once daily for approximately 28 days
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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.
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.
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.
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.
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.
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.
Trial Locations
- Locations (25)
Wcct Global, Llc
🇺🇸Costa Mesa, California, United States
Long Beach Va Medical Center
🇺🇸Long Beach, California, United States
Community Clinical Research Center
🇺🇸Anderson, Indiana, United States
All Medical Research, Llc
🇺🇸Cooper City, Florida, United States
Castlerock Clinical Research Consultants, Llc
🇺🇸Tulsa, Oklahoma, United States
Cardiology Consultants Of Orange County Med. Group Inc
🇺🇸Anaheim, California, United States
Oracle Clinical Research, Inc.
🇺🇸Anaheim, California, United States
King Street Cardiology
🇨🇦Oshawa, Ontario, Canada
Dr. Andy S.C. Lam Medicine Professional
🇨🇦Grimsby, Ontario, Canada
Stroke Prevention & Artherosclerosis Research Centre
🇨🇦London, Ontario, Canada
The Cardiac And Vascular Institute Research Foundation, Llc
🇺🇸Gainesville, Florida, United States
Local Institution
🇨🇦Quebec, Canada
Viacar Recherche Clinique
🇨🇦Greenfield Park, Quebec, Canada
Utah Cardiology P.C
🇺🇸Layton, Utah, United States
Spectrum Clinical Research
🇺🇸Moreno Valley, California, United States
Acrc Cardiology
🇺🇸Lake Worth, Florida, United States
Chase Medical Research, Llc
🇺🇸Waterbury, Connecticut, United States
The Heart Institute At Largo
🇺🇸Largo, Florida, United States
Midwest Heart And Vascular Specialists, Llc.
🇺🇸Overland Park, Kansas, United States
Columbus Regional Research Institute
🇺🇸Columbus, Georgia, United States
Cambridge Medical Trials
🇺🇸Alexandria, Louisiana, United States
Capital Area Research, Llc
🇺🇸Camp Hill, Pennsylvania, United States
Tennessee Center For Clinical Trials
🇺🇸Tullahoma, Tennessee, United States
Fraser Clinical Trials Inc.
🇨🇦New Westminster, British Columbia, Canada
Csss Du Sud De Lanaudiere-Hopital Pierre-Le Gardeur
🇨🇦Terrebonne, Quebec, Canada