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)

July 27, 2012 updated by: Gilead Sciences

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

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).

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Phase 4

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 79 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • Ranexa
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 Names:
  • Ranexa

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
12 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Time to onset of angina during peak ETT at week 12 or last visit
Time Frame: 12 weeks
12 weeks
Time to onset of 1 mm ST-segment depression during peak ETT at week 12 or last visit
Time Frame: 12 weeks
12 weeks
Change from baseline in exercise treadmill duration in the trough ETT at week 12
Time Frame: 12 weeks
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gilead Sciences

Investigators

  • Study Director: Jay Garg, MD, Gilead Sciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2011

Primary Completion (ANTICIPATED)

October 1, 2012

Study Completion (ANTICIPATED)

December 1, 2012

Study Registration Dates

First Submitted

April 11, 2011

First Submitted That Met QC Criteria

April 12, 2011

First Posted (ESTIMATE)

April 13, 2011

Study Record Updates

Last Update Posted (ESTIMATE)

July 31, 2012

Last Update Submitted That Met QC Criteria

July 27, 2012

Last Verified

July 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GS-US-259-0108

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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