A Phase 2, Proof of Concept, Randomized, Placebo-Controlled, Parallel Group Study to Evaluate the Effect of Ranolazine and Dronedarone When Given Alone and in Combination on Atrial Fibrillation Burden in Subjects With Paroxysmal Atrial Fibrillation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 134
- 试验地点
- 1
- 主要终点
- Absolute Change From Baseline in AFB by Week 12
研究概览
简要总结
The primary objective of this study is to evaluate the effect of ranolazine and of low-dose dronedarone when given alone and in combination at different dose levels on atrial fibrillation burden (AFB) over 12 weeks of treatment. AFB is defined as the total time a participant is in atrial tachycardia/atrial fibrillation (AT/AF) expressed as a percentage of total recording time.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females aged 18 years and older
- •Have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
- •History of PAF documented within the prior 12 months
- •Patients with PAF undergoing cardioversion greater than 4 weeks prior to Screening are eligible
- •Implanted (at least 3 months prior to Screening) dual chamber programmable pacemakers with AF detection capabilities
- •AFB ≥ 1% and ≤ 70% between the last clinic evaluation and Screening (minimum of 1 month observation period) and AFB ≥ 2% and ≤ 70% during the Run in period
- •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
排除标准
- •Disease - specific:
- •Persistent AF or Permanent AF
- •History of atrial flutter or atrial tachycardia without successful ablation
- •Other acutely reversible causes of AF, including but not limited to: hyperthyroidism, pericarditis, myocarditis, or pulmonary embolism
- •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.
- •Recent history of left ventricular ejection fraction (LVEF) < 40%
- •Myocardial infarction, unstable angina, or coronary artery bypass graft (CABG) surgery within three months prior to Screening or percutaneous coronary intervention (PCI) within 4 weeks prior to Screening
- •Clinically significant valvular disease in the opinion of the Investigator
- •Stroke within 3 months prior to Screening
- •History of serious ventricular arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation) within 4 weeks prior to Screening
- •Family history of long QT syndrome
- •Corrected QT interval (QTc) ≥ 500 msec (Bazett) at Screening ECG if in sinus rhythm (SR). If in AF, evidence of QTc ≥ 500 msec (Bazett) within 4 weeks prior to Screening
- •Prior heart transplant
- •Cardiac ablation within 4 months prior to Screening, or planned ablation during the course of the study
- •Concomitant medications/food
- •Need for concomitant treatment during the trial, with drugs or products that are strong inhibitors of cytochrome P450 3A (CYP3A), or inducers of CYP3A
- •Such medications should be discontinued 5-half lives prior to the Run-in period
- •Use of grapefruit juice or Seville orange juice during the study
- •Use of Class I and Class III antiarrhythmic drugs other than amiodarone within 5-half lives prior to the Run-in period
- •Use of amiodarone within 3 months prior to Screening
- •Use of drugs that prolong the QT interval
- •Previous use of ranolazine or dronedarone within 2 months prior to screening
- •Prior use of ranolazine or dronedarone which was discontinued for safety or tolerability
- •Use of dabigatran during the study
- •Use of digitalis preparations (eg, digoxin) during the study
- •Use of a greater than 1000 mg total daily dose of metformin during the study
- •Laboratory tests:
- •Hypokalemia (serum potassium < 3.5 mEq/L) at Screening that cannot be corrected to a level of potassium ≥ 3.5 mEq/L prior to randomization
- •Moderate and severe hepatic impairment (ie, Child-Pugh Class B and C), abnormal liver function test defined as alanine aminotransferase (ALT), aspartate aminotransferase (AST), or bilirubin > 2 x upper limit of normal (ULN) at Screening
- •Severe renal impairment defined as creatinine clearance ≤ 30 mL/min at Screening
- •Females who are pregnant or are breastfeeding
- •In the judgment of the Investigator, any clinically-significant ongoing medical condition that might jeopardize the individual's safety or interfere with the study, including participation in another clinical trial within the previous 30 days using a therapeutic modality which could have potential residual effects that might confound the results of this study
- •Any device-related technical issue which in the judgment of the investigator would disrupt adequate data collection or interpretation (eg, anticipated pulse generator change or lead revision)
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Placebo
Ranolazine placebo plus dronedarone placebo for 12 weeks.
干预措施: Ranolazine placebo (Drug)
Placebo
Ranolazine placebo plus dronedarone placebo for 12 weeks.
干预措施: Dronedarone placebo (Drug)
Ranolazine 750 mg
Ranolazine 750 mg plus dronedarone placebo for 12 weeks.
干预措施: Ranolazine (Drug)
Ranolazine 750 mg
Ranolazine 750 mg plus dronedarone placebo for 12 weeks.
干预措施: Dronedarone placebo (Drug)
Dronedarone 225 mg
Ranolazine placebo plus dronedarone 225 mg for 12 weeks.
干预措施: Dronedarone (Drug)
Dronedarone 225 mg
Ranolazine placebo plus dronedarone 225 mg for 12 weeks.
干预措施: Ranolazine placebo (Drug)
Ranolazine 750 mg + Dronedarone 225 mg
Ranolazine 750 mg plus dronedarone 225 mg for 12 weeks.
干预措施: Ranolazine (Drug)
Ranolazine 750 mg + Dronedarone 225 mg
Ranolazine 750 mg plus dronedarone 225 mg for 12 weeks.
干预措施: Dronedarone (Drug)
Ranolazine 750 mg + Dronedarone 150 mg
Ranolazine 750 mg plus dronedarone 150 mg for 12 weeks.
干预措施: Ranolazine (Drug)
Ranolazine 750 mg + Dronedarone 150 mg
Ranolazine 750 mg plus dronedarone 150 mg for 12 weeks.
干预措施: Dronedarone (Drug)
结局指标
主要结局
Absolute Change From Baseline in AFB by Week 12
时间窗: Baseline; Week 12
AFB is defined as the total time a participant is in AT/AF expressed as a percentage of total recording time. Data are presented for baseline-adjusted AFB over 12 weeks of treatment.
Atrial Fibrillation Burden (AFB) at Baseline
时间窗: Baseline
AFB was defined as the total time a participant was in atrial tachycardia (AT)/atrial fibrillation (AF) expressed as a percentage of total recording time. Geometric mean is the mean of log-transformed AFB exponentiated.
Percent Change From Baseline in Atrial Fibrillation Burden (AFB) by Week 12
时间窗: Baseline; Week 12
AFB was defined as the total time a participant was in atrial tachycardia (AT)/atrial fibrillation (AF) expressed as a percentage of total recording time. Data are presented for baseline-adjusted AFB over 12 weeks of treatment. Geometric mean is the mean of log-transformed AFB exponentiated.
次要结局
- Percentage of Participants Who Had ≥ 30%, ≥ 50%, or ≥ 70% Reduction From Baseline in AFB(Week 12)