Pacemaker Holter Assessment of the Effect of BMS-914392 on Atrial Fibrillation Burden

Study Overview
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Brief Summary
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The purpose of the study is to determine whether treatment with BMS-914392 is safe, well tolerated and associated with a reduction of atrial fibrillation burden in patients with paroxysmal atrial fibrillation and permanent pacemaker.

Official Title
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Randomized, Double-Blind, Placebo-Controlled, 4-Way Crossover Study to Evaluate the Safety, Tolerability and Effect on Atrial Fibrillation Burden of BMS-914392 in Patients With Paroxysmal Atrial Fibrillation and Permanent Pacemaker

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Drug: BMS-914392
* Drug: BMS-914392
* Drug: BMS-914392
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Paroxysmal atrial fibrillation (AF) Programmable dual chamber pacemaker with appropriate arrhythmia diagnostics. 1-50% AF burden on pacemaker interrogation at screening. Women of childbearing potential (WOCBP) and men must be using an acceptable method of contraception to avoid pregnancy. Exclusion Criteria: Persistent or permanent AF. AF Burden <1% or > 50%. Current or history of neurological diseases and mental disorders. Ejection Fraction < 45%. Severe mitral or aortic valve dysfunction. TIA (Transient Ischemic Attack) within last 12 months. Acute coronary syndrome in the last 2 months. Previous AF ablation. Cardioversion in last 3 months. Current kidney or liver disease, or current cancer. History of neurological and mental disorders. Major surgery within 4 weeks of first dose (cardiac surgery within 4 months). Screening lab test results outside of allowed limits per protocol. QTcF > 450 msec.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A: BMS-914392<br> | Drug: BMS-914392<br>* Tablets, Oral, 10 mg, Every Day (QD), 20 days<br>|
| Experimental: Treatment B: BMS-914392<br> | Drug: BMS-914392<br>* Tablets, Oral, 10 mg, Three Times Daily (TID), 20 days<br>|
| Experimental: Treatment C: BMS-914392<br> | Drug: BMS-914392<br>* Tablets, Oral, 20 mg, Three Times Daily (TID), 20 days<br>|
| Placebo Comparator: Treatment D: Placebo<br> | Drug: Placebo<br>* Tablets, Oral, 0 mg, Three Times Daily (TID), 20 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Atrial Fibrillation Burden |  | At screening (baseline) | 
| Atrial Fibrillation Burden |  | Prior to randomization to study drug | 
| Atrial Fibrillation Burden |  | On Day 1 of each cross-over period | 
| Atrial Fibrillation Burden |  | On Day 8 of each cross-over period | 
| Atrial Fibrillation Burden |  | On Day 22 of each cross-over period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events and type of adverse events |  | At Day 1 of each cross-over period | 
| Number of participants with adverse events and type of adverse events |  | At Day 8 of each cross-over period | 
| Number of participants with adverse events and type of adverse events |  | At Day 22 of each cross-over period | 
| Number of Atrial fibrillation (AF) episodes |  | At Day 1 of each cross-over period | 
| Number of AF episodes |  | At Day 8 of each cross-over period | 
| Number of AF episodes |  | At Day 22 of each cross-over period | 
| Duration of AF episodes |  | At Day 1 of each cross-over period | 
| Duration of AF episodes |  | At Day 8 of each cross-over period | 
| Duration of AF episodes |  | At Day 22 of each cross-over period | 
| Heart Rate |  | At Day 1 of each cross-over period | 
| Heart Rate |  | At Day 8 of each cross-over period | 
| Heart Rate |  | At Day 22 of each cross-over period | 
| Severity of AF (SAF) scale score at the end of each study period |  | At Day 1 of each cross-over period | 
| Severity of AF (SAF) scale score at the end of each study period |  | At Day 8 of each cross-over period | 
| Severity of AF (SAF) scale score at the end of each study period |  | At Day 22 of each cross-over period | 
| Electrocardiogram (ECG) intervals (PR, QRS, RR, QT, QTc) |  | At Day 1 of each cross-over period | 
| Electrocardiogram (ECG) intervals (PR, QRS, RR, QT, QTc) |  | At Day 8 of each cross-over period | 
| Electrocardiogram (ECG) intervals (PR, QRS, RR, QT, QTc) |  | At Day 22 of each cross-over period | 
| BMS-914392 plasma concentrations and exposures during each study period |  | At Days 1, 8 and 22 of each cross-over period |