Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina (TERISA)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01425359
First received: August 24, 2011
Last updated: October 30, 2014
Last verified: October 2014
  Purpose

This study will evaluate the effect of ranolazine compared to placebo on the average weekly angina frequency in subjects with chronic stable angina and coronary artery disease (CAD) who have a history of type 2 diabetes mellitus (T2DM), and whether ranolazine can reduce the frequency of angina (chest pain) attacks, compared to a placebo. Subjects will be asked to record their daily angina episodes in a diary at the end of each study day. Ranolazine is approved for the treatment of chronic angina, and is not approved for the treatment of T2DM.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: 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:
  • Average Weekly Angina Frequency Over the Last 6 Weeks of Treatment [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

    Average weekly angina frequency was defined as the total number of angina episodes reported during the last 6 weeks of treatment divided by 6 weeks.

    For subjects who terminated with less than 6 weeks of treatment, frequency was calculated as the total number of angina episodes reported during the treatment period divided by the subject's actual duration of treatment.



Secondary Outcome Measures:
  • Average Weekly Frequency of Sublingual Nitroglycerin Use Over the Last 6 Weeks of Treatment [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Average weekly frequency of sublingual nitroglycerin use was defined as the total number reported during the last 6 weeks of treatment divided by the duration corresponding to the last 6 weeks of treatment.

  • Percentage of Weeks Participants Achieved at Least a 50% Reduction in Angina Frequency [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    For each participant, the percentage of the last 6 weeks on treatment during which the angina frequency was less than or equal to 50% of the baseline average weekly angina frequency was determined.

  • Percentage of the Last 6 Weeks on Treatment During Which the Angina Frequency Was ≤ 50% of the Baseline Average Weekly Angina Frequency [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Change From Baseline in the Short-Form 36® (SF-36) Mental and Physical Component Scores [ Time Frame: Up to 8 weeks ] [ Designated as safety issue: No ]
    The range of each health domain score is 0-100, with 0 indicating a poorer health state and 100 indicating a better health state. An increase in score indicates an improvement in health state. Participants were asked to complete the survey at randomization (prior to receiving treatment), and at end of treatment visit (Week 8) or early study drug discontinuation or early termination visit. The survey asked participants for responses specific to the preceding 4 weeks prior to completing the survey.

  • Patient's Global Impression of Change (PGIC) Scale Score [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    The PGIC was completed at the end of treatment/last visit.The PGIC scale measures the change in the participant's overall status since the beginning of the study on a scale ranging from 1 (no change or worse) to 7 (very much improved).


Enrollment: 949
Study Start Date: September 2011
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo

Qualifying phase: Participants will enter a 2-week washout period if needing to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period will be randomized to the treatment period.

Treatment Period: Placebo to match ranolazine (Day 1: 1 tablet in the evening; Days 2-7: 1 tablet twice daily; 2 tablets twice daily thereafter) for up to 8 weeks.

Drug: Ranolazine placebo
Experimental: Ranolazine

Qualifying phase: Participants will enter a 2-week washout period if needing to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period will be randomized to the treatment period.

Treatment period: Ranolazine tablets (Day 1: 1 × 500 tablet in the evening; Days 2-7: 1 × 500 mg twice daily; 2 × 500 mg twice daily thereafter) for up to 8 weeks.

Drug: Ranolazine
Other Name: Ranexa®
Drug: Ranolazine placebo

Detailed Description:

Participants who meet the eligibility criteria at screening will enter a 4-to 6-week Qualifying Period. The allowed concomitant antianginal medication(s) must be maintained at a stable dose throughout the study. Participants will document the number of angina episodes, number of sublingual nitroglycerin doses taken, and a dyspnea score (on a scale from 1 to 5) on a daily basis in a diary. Participants eligible to stay in the study after the Qualifying Period will enter the 8-week double-blind dosing phase. Participants will have study visits at the end of Weeks 2 and 8. Participants will continue to document the number of angina episodes and number of sublingual nitroglycerin doses taken as well as a dyspnea score on a daily basis by the end of each day in their diary. In addition, participants will be called during Week 2 and at the end of Week 5 to encourage compliance. A safety follow-up phone call will be made 14 days after the last study visit or early discontinuation.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent
  • Males and females aged at least 18 years
  • At least a 3-month history of chronic stable angina triggered by physical effort and relieved by rest and/or sublingual nitroglycerin
  • CAD documented by one or more of the following:

    1. Angiographic evidence of ≥ 50% stenosis of one or more major coronary arteries
    2. History of myocardial infarction (MI) documented by positive myocardial muscle creatine kinase (CK-MB) enzymes, troponins, or electrocardiogram (ECG) changes
    3. Cardiac imaging study or exercise test diagnostic for CAD
  • Treatment with up to 2 antianginal therapies at a stable dose for at least 2 weeks prior to the Qualifying Period.
  • Documented history of T2DM
  • Willing to maintain stable tobacco usage habits throughout the study
  • Willing to maintain stable activity levels throughout the study
  • 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:

  • New York Heart Association (NYHA) Class III and IV
  • Acute coronary syndrome in the prior 2 months or planned coronary revascularization during the study period
  • Stroke or transient ischemic attack within 6 months prior to Screening
  • QTc > 500 milliseconds
  • Uncontrolled hypertension (seated systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg)
  • Systolic blood pressure < 100 mmHg
  • Clinically significant hepatic impairment
  • Prior treatment with ranolazine, or known hypersensitivity or intolerance to ranolazine
  • Females who are breastfeeding
  • Positive serum pregnancy test
  • Participation in another investigational drug or device study within 1 month prior to Screening
  • Current treatment with trimetazidine, ivabradine, or nicorandil. Subjects will need to discontinue these medications 2 weeks prior to the Qualifying Period.
  • Current treatment with potent inhibitors of cytochrome (CYP)3A (eg, ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir)
  • Current treatment with CYP3A and P glycoprotein (Pgp) inducers (eg, rifampicin/rifampin, carbamazepine, and St. John's wort [Hypericum perforatum])
  • Current treatment with CYP3A4 substrates with a narrow therapeutic range (eg, cyclosporine, tacrolimus, and sirolimus)
  • Subjects taking simvastatin who cannot reduce the dose to 20 mg once daily or who cannot switch to another statin
  • Current treatment with Class I or III antiarrhythmic medications
  • History of illicit drug use or alcohol abuse within 1 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: NCT01425359

  Show 135 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Patrick Yue, MD Gilead Sciences
  More Information

No publications provided by Gilead Sciences

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01425359     History of Changes
Other Study ID Numbers: GS-US-259-0133
Study First Received: August 24, 2011
Results First Received: October 20, 2014
Last Updated: October 30, 2014
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
Georgia: Ministry of Health
Germany: Federal Institute for Drugs and Medical Devices
Germany: Ethics Commission
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
Ukraine: Ethics Committee
Ukraine: Ministry of Health
Romania: Ethics Committee
Romania: National Medicines Agency
Slovak Republic: Ethics Committee
Slovakia: State Institute for Drug Control
Slovenia: Agency for Medicinal Products - Ministry of Health
Slovenia: Ethics Committee
Bulgaria: Bulgarian Drug Agency
Bulgaria: Ethics committee

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

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

ClinicalTrials.gov processed this record on November 27, 2014