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)

NCT01334203 | Withdrawn Phase 4

• 1 other identifier: GS-US-259-0108
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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).

Conditions

Angina Pectoris; Coronary Artery Disease; Type 2 Diabetes Mellitus

Keywords

Chronic angina; Angina pectoris; Coronary artery disease; Type 2 Diabetes Mellitus; ETT

Outcome Measures

Primary Outcomes (1)

• The primary efficacy endpoint is the change from baseline in exercise treadmill duration in the peak ETT at week 12 or last visit.

  12 weeks

Secondary Outcomes (3)

• 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

Study Arms (2)

Ranolazine

EXPERIMENTAL

Drug: Ranolazine

Placebo

PLACEBO COMPARATOR

Drug: Ranolazine

Interventions

Ranolazine DRUG

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.

Also known as: Ranexa

Placebo; Ranolazine

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

MeSH Terms

Conditions

Angina Pectoris; Coronary Artery Disease; Diabetes Mellitus, Type 2

Interventions

Ranolazine

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Coronary Disease; Arteriosclerosis; Arterial Occlusive Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jay Garg, MD

  Gilead Sciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: April 11, 2011
• First Posted: April 13, 2011
• Study Start: May 1, 2011
• Primary Completion: October 1, 2012
• Study Completion: December 1, 2012
• Last Updated: July 31, 2012

Record last verified: 2012-07