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.
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
Allocation
RANDOMIZED
Purpose
OTHER
Masking
QUADRUPLE
Enrollment
158
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.
Time frame: Day 8 to Day 29
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.
Time frame: Up to Day 50
Maximum Observed Concentarion (Cmax) of BMS-919373
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
Trough Observed Concentration (Cmin) of BMS-919373
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Cardiology Consultants Of Orange County Med. Group Inc
Anaheim, California, United States
Oracle Clinical Research, Inc.
Anaheim, California, United States
Wcct Global, Llc
Costa Mesa, California, United States
Long Beach Va Medical Center
Long Beach, California, United States
Spectrum Clinical Research
Moreno Valley, California, United States
Chase Medical Research, Llc
Waterbury, Connecticut, United States
All Medical Research, Llc
Cooper City, Florida, United States
The Cardiac And Vascular Institute Research Foundation, Llc
Gainesville, Florida, United States
Acrc Cardiology
Lake Worth, Florida, United States
The Heart Institute At Largo
Largo, Florida, United States
...and 25 more locations
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)
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.
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)
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.
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)
Absorption Rate Constant (Ka) of BMS-919373
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)
Average Concentration (Cavg) of BMS-919373 at Steady State
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)
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.
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)
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.
Time frame: 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.
Time frame: 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.
Time frame: Day 8 to Day 29