E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003661 |
E.1.2 | Term | Atrial fibrillation paroxysmal |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10034039 |
E.1.2 | Term | Paroxysmal atrial fibrillation |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to assess, by the use of long term beat to beat pacemaker monitoring, the effect of BMS-914392 on the reduction of placebo-corrected AF burden (% of time spent in AF) in pacemaker subjects with paroysmal AF. |
|
E.2.2 | Secondary objectives of the trial |
• To assess the effect of BMS-914392 on the total number of AF episodes, average duration of AF per episode, and average sinus rhythm duration derived from continuous pacemaker monitoring.
• To assess the effect of BMS-914392 on subject-perceived AF-related symptoms through self-reporting using the Canadian Cardiovascular Society Atrial Fibrillation Severity Scale (CCS-AFSS).
• To assess the safety and tolerability of BMS-914392.
• To assess the effect of BMS-914392 on PR, QRS, RR, QT, and QTc intervals derived from 12-lead ECGs for periods of sinus rhythm.
• To assess the pharmacokinetics of BMS-914392 on Day 1 and Day 8 of Period 1, 2, 3, and 4. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Women of childbearing potential (WOCBP) and men must be using an acceptable method of contraception to avoid pregnancy
• Paroxysmal atrial fibrillation (AF) within 6 month prior to screening.
• Programmable dual chamber pacemaker with appropriate arrhythmia diagnostics that was implanted for a primary or secondary indication at least 1 month with a stable peacemaker assessment prior to screening.
a. 1-50% AF burden (% of time spend in AF) on pacemaker interrogation at screening.
• Any oral anticoagulant approved for use in atrial fibrillation for prevention of stroke or other embolic disease.
• Able to tolerate withdrawal of antiarrhythmic therapy.
• Able to tolerate pacemaker antiarrhythmic algorithms turned off.
• Clinically stable at the time of randomization as determined by the investigator. |
|
E.4 | Principal exclusion criteria |
• AF burden <1% and > 50% on pacemaker interrogation prior to first dosing.
• Permanent AF.
• Development of persistent AF prior to first dosing.
• Any significant acute or chronic medical illness that is severe, progressive or uncontrolled at the time of screening.
• Current or history of neurological diseases and mental disorders, including syncope, convulsive disorders such as epilepsy, central thrombosis and cerebral embolism, stroke, or accidents involving brain injuries.
• History of TIA in the last 12 months.
• History of Ventricular Arrythmia.
• Cardioversion within 3 months of study drug administration. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
• AF burden: percent of time in which a subject is in AF
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Measured from Day 8 to Day 22 of Periods 1, 2, 3, 4 and Day 1 to Day 8 of period 5.
|
|
E.5.2 | Secondary end point(s) |
• Total number of AF episodes
• Average duration of AF per episode
• Average sinus rhythm duration
• Self-reported AF symptoms
• ECG intervals derived from 12-lead ECGs
• Safety assessments will be based on medical review of adverse event reports and the results of vital sign measurements, 12-lead ECGs, physical and neurological examinations and clinical laboratory tests. The incidence of observed adverse events will be tabulated and reviewed for potential significance and clinical importance.
• Pharmacokinetic Measures:
Observed Cmin at steady state (Day 7) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Throughout of the Treatment Period |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |