Paroxysmal Atrial Fibrillation MedDRA version: 20.0 Level: LLT Classification code 10034039 Term: Paroxysmal atrial fibrillation System Organ Class: 100000004849
Conditions
Interventions
Trade Name: Ranexa
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: RANOLAZINE
CAS Number: 95635-55-5
Concentration un
Sponsors
Gilead Sciences, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Males and females aged 18 years and older 2. Have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures 3. History of PAF documented within the prior 12 months — Patients with PAF undergoing cardioversion greater than 4 weeks prior to Screening are eligible 4. Implanted (at least 3 months prior to Screening) dual chamber programmable pacemakers with AF detection capabilities 5. AFB = 1% and = 70% between the last clinic evaluation and Screening (minimum of 1 month observation period) and AFB = 3% and = 50% during the 4-week Run-in period 6. Sexually active females of childbearing potential must agree to utilize effective methods of contraception during heterosexual intercourse throughout the treatment period and for 14 days following discontinuation of the study medication Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: 1. History of persistent or permanent atrial fibrillation, or history of atrial flutter or atrial tachycardia without successful ablation 2. Other acutely reversible causes of AF, including but not limited to: hyperthyroidism, pericarditis, myocarditis, or pulmonary embolism 3. New York Heart Association (NYHA) Class III and IV heart failure or NYHA Class II heart failure with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic within 4 weeks prior to Screening. 4. Myocardial infarction, unstable angina, or coronary artery bypass graft surgery within three months prior to Screening or percutaneous coronary intervention within 4 weeks prior to Screening 5. Clinically significant valvular disease in the opinion of the Investigator 6. Stroke within 3 months prior to Screening 7. History of serious ventricular arrhythmias (e.g., sustained ventricular tachycardia, ventricular fibrillation) within 4 weeks prior to Screening 8. QTc = 500 msec (Bazett) at Screening ECG if in sinus rhythm (SR). If in atrial fibrillation, evidence of QTc = 500 msec (Bazett) within 4 weeks prior to Screening 9. Prior heart transplant 10 Electrical cardioversion within 4 weeks prior to Screening 11. Need for concomitant treatment during the trial, with drugs or products that are strong inhibitors of CYP3A, or inducers of CYP3A (such medications should be discontinued 5 half lives prior to study entry) 12. Use of grapefruit juice during the study 13. Use of Class I and Class III antiarrhythmic drugs other than amiodarone within 5-half lives prior to the Run-in period 14. Use of amiodarone within 3 months prior to Screening 15. Use of drugs that prolong the QT interval 16. No previous use of ranolazine or dronedarone within 6 months prior to screening 17. Prior use of ranolazine or dronedarone which was discontinued for safety or tolerability 18. Use of dabigatran during the study 19. Uncorrected hypokalemia (serum potassium 2 X ULN at Screening 21. Severe renal impairment defined as creatinine clearance = 30 mL/min at Screening 22. Females who are pregnant or are breastfeeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of ranolazine and of low dose dronedarone when given alone and in combination at different dose levels on AFB over 12 weeks of treatment AFB is defined as the total time a subject is in atrial tachycardia/atrial fibrillation (AT/AF) expressed as a percentage of total recording time. ; Secondary Objective: To evaluate the effect of ranolazine and of dronedarone when given alone and in combination at different dose levels on: — Atrial fibrillation burden for each visit period — Number of atrial fibrillation episodes, duration of atrial fibrillation episodes, and ventricular rate during atrial fibrillation episodes — Ventricular rate over 12-weeks of treatment and for each visit period — Percentage of ventricular pacing — Percentage of atrial pacing — Incidence of persistent atrial fibrillation — Incidence of electrical cardioversion — Incidence of symptomatic episodes To determine the percentage of subjects who have = 30% (= 50%) reduction from baseline in AFB To determine the percentage of subjects who have total duration of AF episodes = 5.5 hours per day at any point during the treatment period ;Primary end point(s): Change from baseline in atrial fibrillation burden (both percent change and absolute change).;Timepoint(s) of evaluation of this end point: 12 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Change from baseline in atrial fibrillation burden for each visit period 2. Change from baseline in number of AF episodes, duration of AF episodes, and average ventricular rate for each AF episode 3. Change from baseline in ventricular rate for each visit period 4. Percent ventricular pacing for each visit period 5. Percent atrial pacing 6. Incidence of persistent atrial fibrillation 7. Incidence of electrical cardioversion 8. Incidence of symptomatic episodes ;Timepoint(s) of evaluation of this end point: 4, 8 and 12 weeks | — |
Countries
Germany, Israel, Italy, Netherlands, Poland, United Kingdom, United States
Contacts
Public ContactInternational Regulatory Affairs
Gilead Sciences International Ltd
Outcome results
None listed