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

• ClinicalTrials.gov Identifier: NCT02156076
• Recruitment Status: Terminated
• First Posted: June 5, 2014
• Results First Posted: May 22, 2019
• Last Update Posted: July 31, 2019
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: May 12, 2014
• First Posted Date: June 5, 2014
• Results First Submitted Date: March 21, 2019
• Results First Posted Date: May 22, 2019
• Last Update Posted Date: July 31, 2019
• Actual Study Start Date: July 25, 2014
• Actual Primary Completion Date: June 1, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 30, 2019)

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

• Original Primary Outcome Measures (submitted: June 3, 2014): Percent change from baseline in Atrial Fibrillation Burden (percent of time in which a subject is in Atrial Fibrillation) [ Time Frame: Day 8 to Day 29 ]

Current Secondary Outcome Measures (submitted: April 30, 2019)

• Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-related AEs and Death [ Time Frame: 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 [ Time Frame: 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 [ 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) ]
  Ctrough is defined as the minimum estimated plasma concentration at steady state.
• Oral Clearance (CL/F) of BMS-919373 [ 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) ]
  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 [ 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) ]
  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 [ 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) ]
  Ka is the absorption rate constant.
• Average Concentration (Cavg) of BMS-919373 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) ]
  Cavg is defines as the average concentration at steady state.
• Area Under the Concentration-time Curve (AUC) at Steady State of BMS-919373 [ 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) ]
  AUC is defined as the area under the concentration-time curve at steady state.
• Time to First Atrial Fibrillation Recurrence (TTFR) (Symptomatic or Asymptomatic) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: June 3, 2014)

• Safety assessments will be based on review of adverse events, vital sign measurements, ECGs, physical examinations, and clinical laboratory tests collected at specified time points and continuous monitoring of safety events of special interest [ Time Frame: From initiation of study drug until follow up visit (approximately 50 days) ]
• Maximum observed concentration (Cmax) of BMS-919373 [ Time Frame: Day 1 and Day 22 ]
• Trough Observed Concentration (Cmin) of BMS-919373 [ Time Frame: Day 8, Day 22, and Day 29 ]
  Estimates of individual exposure parameters will be derived from the population pharmacokinetics (PK) model
• Oral Clearance (CL/F) of BMS-919373 [ Time Frame: Day 36, Day 50 ]
  PK data collected will be used to develop a population PK model to estimate model-based parameters
• Central Volume of Distribution (Vc/F) of BMS-919373 [ Time Frame: Day 8, Day 22, and Day 29 ]
  PK data collected will be used to develop a population PK model to estimate model-based parameters
• Absorption Rate Constant (Ka) of BMS-919373 [ Time Frame: Day 8, Day 22, and Day 29 ]
  PK data collected will be used to develop a population PK model to estimate model-based parameters
• Average concentration (Cavg) of BMS-919373 [ Time Frame: Day 8, Day 22, and Day 29 ]
  Estimates of individual exposure parameters will be derived from the population PK model
• Area Under the Concentration-time Curve (AUC) at Steady State of BMS-919373 [ Time Frame: Day 8, Day 22, and Day 29 ]
  Estimates of individual exposure parameters will be derived from the population PK model
• Efficacy based on time to first AF recurrence (symptomatic or asymptomatic) [ Time Frame: From initiation of study drug until follow up visit (approximately 50 days) ]
• Efficacy based on number of AF episodes [ Time Frame: From initiation of study drug until follow up visit (approximately 50 days) ]
• Efficacy based on average duration of AF per episode [ Time Frame: From initiation of study drug until follow up visit (approximately 50 days) ]
• Efficacy based on average sinus rhythm duration [ Time Frame: From initiation of study drug until follow up visit (approximately 50 days) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Other
• Condition: Paroxysmal Atrial Fibrillation

Intervention

• Drug: BMS-919373
• Drug: Placebo (Matching with BMS-919373)

Study Arms

• Placebo Comparator: Arm A: Placebo (Matching with BMS-919373)
  Placebo (Matching with BMS-919373) 0 mg tablets orally once daily for approximately 28 Days
  Intervention: Drug: Placebo (Matching with BMS-919373)
• Experimental: Arm B: BMS-919373
  BMS-919373 3 mg tablets orally once daily for approximately 28 days
  Intervention: Drug: BMS-919373
• Experimental: Arm C: BMS-919373
  BMS-919373 5 mg tablets orally once daily for approximately 28 days
  Intervention: Drug: BMS-919373
• Experimental: Arm D: BMS-919373
  BMS-919373 12 mg tablets orally once daily for approximately 28 days
  Intervention: Drug: BMS-919373

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: April 30, 2019): 158
• Original Estimated Enrollment (submitted: June 3, 2014): 80
• Actual Study Completion Date: June 1, 2016
• Actual Primary Completion Date: June 1, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT02156076
• Other Study ID Numbers: CV205-005
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Bristol-Myers Squibb
• Study Sponsor: Bristol-Myers Squibb
• Collaborators: Not Provided

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

• PRS Account: Bristol-Myers Squibb
• Verification Date: July 2019