Clinical trial NCT01356914: Pacemaker Holter Assessment of the Effect of BMS-914392 on Atrial Fibrillation Burden
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Atrial Fibrillation
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2011-05-20
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Atrial Fibrillation Burden
timeFrame: At screening (baseline)
measure: Atrial Fibrillation Burden
timeFrame: Prior to randomization to study drug
measure: Atrial Fibrillation Burden
timeFrame: On Day 1 of each cross-over period
measure: Atrial Fibrillation Burden
timeFrame: On Day 8 of each cross-over period
measure: Atrial Fibrillation Burden
timeFrame: On Day 22 of each cross-over period
Secondary outcomes:
measure: Number of participants with adverse events and type of adverse events
timeFrame: At Day 1 of each cross-over period
measure: Number of participants with adverse events and type of adverse events
timeFrame: At Day 8 of each cross-over period
measure: Number of participants with adverse events and type of adverse events
timeFrame: At Day 22 of each cross-over period
measure: Number of Atrial fibrillation (AF) episodes
timeFrame: At Day 1 of each cross-over period
measure: Number of AF episodes
timeFrame: At Day 8 of each cross-over period
measure: Number of AF episodes
timeFrame: At Day 22 of each cross-over period
measure: Duration of AF episodes
timeFrame: At Day 1 of each cross-over period
measure: Duration of AF episodes
timeFrame: At Day 8 of each cross-over period
measure: Duration of AF episodes
timeFrame: At Day 22 of each cross-over period
measure: Heart Rate
timeFrame: At Day 1 of each cross-over period
measure: Heart Rate
timeFrame: At Day 8 of each cross-over period
measure: Heart Rate
timeFrame: At Day 22 of each cross-over period
measure: Severity of AF (SAF) scale score at the end of each study period
timeFrame: At Day 1 of each cross-over period
measure: Severity of AF (SAF) scale score at the end of each study period
timeFrame: At Day 8 of each cross-over period
measure: Severity of AF (SAF) scale score at the end of each study period
timeFrame: At Day 22 of each cross-over period
measure: Electrocardiogram (ECG) intervals (PR, QRS, RR, QT, QTc)
timeFrame: At Day 1 of each cross-over period
measure: Electrocardiogram (ECG) intervals (PR, QRS, RR, QT, QTc)
timeFrame: At Day 8 of each cross-over period
measure: Electrocardiogram (ECG) intervals (PR, QRS, RR, QT, QTc)
timeFrame: At Day 22 of each cross-over period
measure: BMS-914392 plasma concentrations and exposures during each study period
timeFrame: At Days 1, 8 and 22 of each cross-over period
Other outcomes:
Locations:
city: Eastbourne
country: United Kingdom
facility: Eastbourne General Hospital
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: 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.