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

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

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.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: BMS-914392; Drug: BMS-914392; Drug: BMS-914392; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Eastbourne, United Kingdom, BN21 2UD
    • Eastbourne General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

General Publications

• Podd SJ, Freemantle N, Furniss SS, Sulke N. First clinical trial of specific IKACh blocker shows no reduction in atrial fibrillation burden in patients with paroxysmal atrial fibrillation: pacemaker assessment of BMS 914392 in patients with paroxysmal atrial fibrillation. Europace. 2016 Mar;18(3):340-6. doi: 10.1093/europace/euv263. Epub 2015 Oct 12.

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: April 15, 2011
• First Submitted That Met QC Criteria: May 19, 2011
• First Posted (Estimate): May 20, 2011

Study Record Updates

• Last Update Posted (Estimate): October 12, 2015
• Last Update Submitted That Met QC Criteria: September 23, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: CV203-010; 2010-022947-39 (EudraCT Number)