A Study on the Effects of Ranolazine on Exercise Duration in Subjects With Chronic Stable Angina and Coronary Artery Disease (CAD) With Type 2 Diabetes Mellitus (T2DM)

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by:
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01334203
First received: April 11, 2011
Last updated: July 27, 2012
Last verified: July 2012
  Purpose

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).


Condition Intervention Phase
Angina Pectoris
Coronary Artery Disease
Type 2 Diabetes Mellitus
Drug: Ranolazine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • The primary efficacy endpoint is the change from baseline in exercise treadmill duration in the peak ETT at week 12 or last visit. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to onset of angina during peak ETT at week 12 or last visit [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Time to onset of 1 mm ST-segment depression during peak ETT at week 12 or last visit [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in exercise treadmill duration in the trough ETT at week 12 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: May 2011
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ranolazine Drug: Ranolazine

Subjects will be randomized to either ranolazine 500 mg twice daily up-titrated on Day 4 to 1000 mg administered orally twice a day or matching placebo for the 12 week treatment period.

Subjects receiving diltiazem or verapamil as their concomitant antianginal medication will receive ranolazine 500 mg or placebo administered orally twice a day.

Other Name: Ranexa
Placebo Comparator: Placebo Drug: Ranolazine

Subjects will be randomized to either ranolazine 500 mg twice daily up-titrated on Day 4 to 1000 mg administered orally twice a day or matching placebo for the 12 week treatment period.

Subjects receiving diltiazem or verapamil as their concomitant antianginal medication will receive ranolazine 500 mg or placebo administered orally twice a day.

Other Name: Ranexa

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01334203

Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Jay Garg, MD Gilead Sciences
  More Information

No publications provided

Responsible Party: Jay Garg, MD, Director, Clinical Research, Gilead Sciences, Inc.
ClinicalTrials.gov Identifier: NCT01334203     History of Changes
Other Study ID Numbers: GS-US-259-0108
Study First Received: April 11, 2011
Last Updated: July 27, 2012
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Canada: Health Canada
Canada: Ethics Review Committee
Belarus: Ministry of Health
Czech Republic: Ethics Committee
Czech Republic: State Institute for Drug Control
Denmark: Danish Medicines Agency
Denmark: Ethics Committee
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: National Consultative Ethics Committee for Health and Life Sciences
Georgia: Ministry of Health
Germany: Federal Institute for Drugs and Medical Devices
Israel: Ethics Commission
Israel: Ministry of Health
Poland: Ethics Committee
Poland: The Central Register of Clinical Trials
Russia: Ethics Committee
Russia: Ministry of Health of the Russian Federation
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
Serbia: Ethics Committee
Singapore: Domain Specific Review Boards
Singapore: Health Sciences Authority
Sweden: Medical Products Agency
Sweden: Regional Ethical Review Board
Ukraine: Ethics Committee
Ukraine: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Keywords provided by Gilead Sciences:
Chronic angina
Angina pectoris
Coronary artery disease
Type 2 Diabetes Mellitus
ETT

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Angina Pectoris
Angina, Stable
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Chest Pain
Pain
Signs and Symptoms
Ranolazine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 19, 2014