NCT01334203撤回4 期
A Phase 4, Randomized, Double-Blind, Placebo-Controlled, Parallel Study of Ranolazine in Subjects With Chronic Stable Angina and Coronary Artery Disease With a History of Type 2 Diabetes Mellitus
适应症
干预措施
相关药物
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 主要终点
- The primary efficacy endpoint is the change from baseline in exercise treadmill duration in the peak ETT at week 12 or last visit.
研究概览
简要总结
This study will evaluate the efficacy of ranolazine compared to placebo on duration of exercise assessed by exercise tolerance testing (ETT) at anticipated peak ranolazine plasma concentration after 12 weeks of treatment in subjects with chronic stable angina and coronary artery disease (CAD) who have a history of type 2 diabetes mellitus (T2DM).
详细描述
This study will evaluate the efficacy of ranolazine compared to placebo on duration of exercise assessed by exercise tolerance testing (ETT) at anticipated peak ranolazine plasma concentration after 12 weeks of treatment in subjects with chronic stable angina and coronary artery disease (CAD) who have a history of type 2 diabetes mellitus (T2DM). This is a randomized, double-blind, placebo-controlled, parallel group study in subjects with chronic stable angina and CAD receiving a stable dose of a single concomitant antianginal medication who also have a history of T2DM; allowed antianginals will be a beta-blocker (atenolol or metoprolol) or a calcium-channel blocker.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent
- •Males and females aged 18 to 79 years
- •Able to perform a Sheffield Modified Bruce Treadmill Exercise Protocol
- •At least a 3-months history of chronic stable angina triggered by physical effort and relieved by rest and/or sublingual nitroglycerin
- •Coronary artery disease documented by one or more of the following:
- •Angiographic evidence of ≥ 50% stenosis of one or more major coronary arteries
- •History of myocardial infarction (MI) documented by positive CK-MB enzymes, troponins, or ECG changes
- •Cardiac nuclear scan studies diagnostic of CAD, e.g., thallium scan or ECHO with stress or pharmacologic interventions (adenosine, dipyridamole, etc.)
- •Stable treatment with one of the following antianginal medications for at least 4 weeks prior to Screening:
- •beta-blocker (atenolol up to 50 mg daily or metoprolol up to 100 mg daily)
- •dihydropyridine calcium-channel blocker (amlodipine up to 5 mg daily or nifedipine up to 30 mg daily)
- •non-dihydropyridine calcium-channel blocker (diltiazem 180 to 360 mg daily or verapamil 180 to 360 mg daily)
- •Willingness to discontinue other antianginals and be treated with one of the allowed antianginal therapies
- •Documented history of type 2 diabetes mellitus
- •Females of childbearing potential must agree to utilize highly effective contraception methods from Screening throughout the duration of study treatment and for 14 days following the last dose of study drug.
排除标准
- •Inability to exercise or having exercise limitation due to other co-morbidities that may interfere with ability to perform required ETT (e.g., morbid obesity, significant chronic lung disease, prior hospitalization for acute exacerbation of chronic lung disease or home oxygen use, chronic oral steroid therapy that can limit exercise capacity, osteoarthritis, peripheral artery disease, etc.)
- •Any absolute contraindication to ETT
- •Presence of electrocardiographic or other abnormalities that interfere with ECG interpretation or may cause a false positive stress test (e.g., ≥ 1 mm horizontal or down-sloping ST segment depression at rest in any standard ECG lead, Lown-Ganong-Levine syndrome, Wolff-Parkinson-White syndrome, left bundle branch block, left ventricular hypertrophy with repolarization abnormality, ventricular pacemaker, etc.)
- •Decompensated heart failure
- •Clinically significant valvular heart disease or congenital cardiac defects
- •Acute coronary syndrome in the prior 2 months or coronary revascularization within the prior 6 months or planned coronary revascularization during the study period
- •Stroke or transient ischemic attack within 6 months prior to Screening
- •History of serious ventricular dysrhythmias or a history of life-threatening ventricular arrhythmia
- •Atrial fibrillation
- •QTc > 0.5 seconds
- •Hypertrophic cardiomyopathy
- •Uncontrolled hypertension (seated systolic blood pressure > 180 mm Hg or diastolic blood pressure > 110 mm Hg)
- •Systolic blood pressure < 90 mm Hg
- •Inability to discontinue current antianginal medications and remain on one allowed antianginal therapy
- •Clinically significant hepatic impairment
- •Creatinine clearance (CLCr) < 30 ml/min
- •Prior treatment with ranolazine
- •Participation in another investigational drug or device study within 1 month prior to Screening
- •Females who are breastfeeding
- •Positive serum pregnancy test
- •Current treatment with potent inhibitors of CYP3A (e.g., ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir)
- •Current treatment with CYP3A and P glycoprotein (Pgp) inducers (e.g., rifampicin/rifampin, carbamazepine, St. John's wort)
- •History of illicit drug use or alcohol abuse within one year of screening
- •Any other conditions that, in the opinion of the investigator, are likely to prevent compliance with the study protocol or pose a safety concern if the subject participates in the study
研究组 & 干预措施
Ranolazine
Experimental
干预措施: Ranolazine (Drug)
Placebo
Placebo Comparator
干预措施: Ranolazine (Drug)
结局指标
主要结局
The primary efficacy endpoint is the change from baseline in exercise treadmill duration in the peak ETT at week 12 or last visit.
时间窗: 12 weeks
次要结局
- Time to onset of angina during peak ETT at week 12 or last visit(12 weeks)
- Time to onset of 1 mm ST-segment depression during peak ETT at week 12 or last visit(12 weeks)
- Change from baseline in exercise treadmill duration in the trough ETT at week 12(12 weeks)
研究者
相似试验
已完成
3 期
Ranolazine for Incomplete Vessel Revascularization Post-Percutaneous Coronary Intervention (PCI)Angina PectorisCoronary Artery DiseaseNCT01442038Gilead Sciences2,651
已完成
4 期
Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable AnginaType 2 Diabetes MellitusCoronary Artery DiseaseAngina PectorisNCT01425359Gilead Sciences949
已完成
2 期
Ranolazine in Atrial Fibrillation Following An ELectricaL CardiOversionPersistent Atrial FibrillationNCT01534962Menarini Group241
已完成
2 期
Study to Evaluate the Effect of Ranolazine and Dronedarone When Given Alone and in Combination in Patients With Paroxysmal Atrial FibrillationAtrial FibrillationNCT01522651Gilead Sciences134
终止
4 期
Study of Ranexa in Patients With Coronary Artery Disease and Painful PolyneuropathyPainPeripheral Nervous System DiseasesCoronary Artery DiseasePolyneuropathyNCT00832572Gilead Sciences5