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

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ClinicalTrials.gov Identifier: NCT01425359
Recruitment Status : Completed
First Posted : August 30, 2011
Results First Posted : November 4, 2014
Last Update Posted : November 4, 2014
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE August 24, 2011
First Posted Date  ICMJE August 30, 2011
Results First Submitted Date  ICMJE October 20, 2014
Results First Posted Date  ICMJE November 4, 2014
Last Update Posted Date November 4, 2014
Study Start Date  ICMJE September 2011
Actual Primary Completion Date October 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 30, 2014)
Average Weekly Angina Frequency Over the Last 6 Weeks of Treatment [ Time Frame: 6 weeks ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 26, 2011)
The average weekly angina frequency over the last 6 weeks of treatment [ Time Frame: 6 weeks ]
Change History Complete list of historical versions of study NCT01425359 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 30, 2014)
  • Average Weekly Frequency of Sublingual Nitroglycerin Use Over the Last 6 Weeks of Treatment [ Time Frame: 6 weeks ]
    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 ]
    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 ]
  • Change From Baseline in the Short-Form 36® (SF-36) Mental and Physical Component Scores [ Time Frame: Up to 8 weeks ]
    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 ]
    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).
Original Secondary Outcome Measures  ICMJE
 (submitted: August 26, 2011)
  • Average Weekly Frequency of Sublingual Nitroglycerin Use Over the Last 6 Weeks of Treatment [ Time Frame: 6 weeks ]
  • Angina-free days over the last 6 weeks of treatment [ Time Frame: 6 weeks ]
  • Proportion of subjects achieving at least a 50% reduction in the average weekly angina frequency [ Time Frame: 6 weeks ]
  • Change from baseline in the SF-36 Mental and Physical Component Scores [ Time Frame: 8 weeks ]
  • PGIC scale score [ Time Frame: 8 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina
Official Title  ICMJE 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
Brief Summary 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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Angina Pectoris
  • Coronary Artery Disease
  • Type 2 Diabetes Mellitus
Intervention  ICMJE
  • Drug: Ranolazine
    Other Name: Ranexa®
  • Drug: Ranolazine placebo
Study Arms  ICMJE
  • 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.

    Intervention: 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.

    Interventions:
    • Drug: Ranolazine
    • Drug: Ranolazine placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 5, 2012)
949
Original Estimated Enrollment  ICMJE
 (submitted: August 26, 2011)
900
Actual Study Completion Date  ICMJE October 2012
Actual Primary Completion Date October 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belarus,   Bulgaria,   Canada,   Czech Republic,   Georgia,   Germany,   Israel,   Poland,   Russian Federation,   Serbia,   Slovakia,   Slovenia,   Ukraine,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01425359
Other Study ID Numbers  ICMJE GS-US-259-0133
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Gilead Sciences
Study Sponsor  ICMJE Gilead Sciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Patrick Yue, MD Gilead Sciences
PRS Account Gilead Sciences
Verification Date October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP