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

Primary Purpose

Paroxysmal Atrial Fibrillation

Status

Terminated

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

BMS-919373

Placebo (Matching with BMS-919373)

About this trial

This is an interventional other trial for Paroxysmal Atrial Fibrillation

Eligibility Criteria

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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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Experimental

Arm Label

Arm A: Placebo (Matching with BMS-919373)

Arm B: BMS-919373

Arm C: BMS-919373

Arm D: BMS-919373

Arm Description

Placebo (Matching with BMS-919373) 0 mg tablets orally once daily for approximately 28 Days

BMS-919373 3 mg tablets orally once daily for approximately 28 days

BMS-919373 5 mg tablets orally once daily for approximately 28 days

BMS-919373 12 mg tablets orally once daily for approximately 28 days

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Maximum Observed Concentarion (Cmax) of BMS-919373

Cmax is defined as the maximum observed concentration of BMS-919373.

Trough Observed Concentration (Cmin) of BMS-919373

Ctrough is defined as the minimum estimated plasma concentration at steady state.

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.

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.

Absorption Rate Constant (Ka) of BMS-919373

Ka is the absorption rate constant.

Average Concentration (Cavg) of BMS-919373 at Steady State

Cavg is defines as the average concentration at steady state.

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 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.

Total Number of Atrial Fibrillation Episodes

The total number AF episodes were derived from AF episode histogram data over the monitoring period.

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.

Full Information

NCT ID

NCT02156076

First Posted

May 12, 2014

Last Updated

July 29, 2019

Sponsor

Bristol-Myers Squibb

1. Study Identification

Unique Protocol Identification Number

NCT02156076

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2019

Overall Recruitment Status

Terminated

Why Stopped

Sponsor decision based on business reasons, unrelated to safety

Study Start Date

July 25, 2014 (Actual)

Primary Completion Date

June 1, 2016 (Actual)

Study Completion Date

June 1, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Paroxysmal Atrial Fibrillation

7. Study Design

Primary Purpose

Other

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

158 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm A: Placebo (Matching with BMS-919373)

Arm Type

Placebo Comparator

Arm Description

Placebo (Matching with BMS-919373) 0 mg tablets orally once daily for approximately 28 Days

Arm Title

Arm B: BMS-919373

Arm Type

Experimental

Arm Description

BMS-919373 3 mg tablets orally once daily for approximately 28 days

Arm Title

Arm C: BMS-919373

Arm Type

Experimental

Arm Description

BMS-919373 5 mg tablets orally once daily for approximately 28 days

Arm Title

Arm D: BMS-919373

Arm Type

Experimental

Arm Description

BMS-919373 12 mg tablets orally once daily for approximately 28 days

Intervention Type

Drug

Intervention Name(s)

BMS-919373

Intervention Type

Drug

Intervention Name(s)

Placebo (Matching with BMS-919373)

Primary Outcome Measure Information:

Title

Percent Change From Baseline in Atrial Fibrillation Burden (AFB) as Assessed by SEEQ Mobile Cardiac Telemetry (MCT) System

Description

Time Frame

Day 8 to Day 29

Secondary Outcome Measure Information:

Title

Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-related AEs and Death

Description

Time Frame

Up to Day 50

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

Title

Trough Observed Concentration (Cmin) of BMS-919373

Description

Ctrough is defined as the minimum estimated plasma concentration at steady state.

Time Frame