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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

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.

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

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 949 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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
Study Start Date : September 2011
Actual Primary Completion Date : October 2012
Actual Study Completion Date : October 2012

Resource links provided by the National Library of Medicine

Drug Information available for: Ranolazine

Arm Intervention/treatment
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



Primary Outcome Measures :
  1. 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.



Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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 ]
  4. 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.

  5. 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).



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01425359


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Locations
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United States, Arkansas
Cardiology and Medicine Clinic
Little Rock, Arkansas, United States, 72204
United States, California
Merced Heart Associates
Merced, California, United States, 95340
Spectrum Clinical Research Institute, Inc
Moreno Valley, California, United States, 92553
Sacramento Heart and Vascular Research Center
Sacramento, California, United States, 95825
United States, Florida
South Florida Research Solutions, LLC
Hollywood, Florida, United States, 33021
Baptist Heart Specialist
Jacksonville, Florida, United States, 32207
Clinical Research of Central Florida
Winter Haven, Florida, United States, 33880
United States, Georgia
Masters of Clinical Research, Inc.
Augusta, Georgia, United States, 30909
Columbus Cardiology Associates
Columbus, Georgia, United States, 31909
United States, Kentucky
Central Cardiology Associates
Elizabethtown, Kentucky, United States, 42701
Research Integrity, LLC
Owensboro, Kentucky, United States, 42303
United States, Louisiana
Alexandria Cardiology Clinic
Alexandria, Louisiana, United States, 71301
Clinical Trials Management, LLC
Mandeville, Louisiana, United States, 70471
United States, Michigan
Endeavor Medical Research, PLC
Alpena, Michigan, United States, 49707
United States, Minnesota
Minneapolis Heart Institute Foundation
Minneapolis, Minnesota, United States, 55407
United States, New Jersey
Cross Country Cardiology
Edgewater, New Jersey, United States, 07020
United States, Tennessee
Kore CV Research
Jackson, Tennessee, United States, 38305
Wellmont Cardiovascular Associates Heart Institute
Johnson City, Tennessee, United States, 37604
United States, Texas
Med-Tech Research
Houston, Texas, United States, 77024
Humble Cardiology Associates
Humble, Texas, United States, 77338
Belarus
State Institution "Gomel regional clinical hospital"
Gomel, Belarus, 246029
State Inst Rep Scientific and Practical center
Minsk, Belarus, 220036
Bulgaria
Diagnostic Consultative Center, Ascendent Cardiological Out-Patient Office
Sofia, Bulgaria, 1202
MHAT "Tsar Boris III"
Sofia, Bulgaria, 1233
National Cardiology Center, Cardiology Clinic - III
Sofia, Bulgaria, 1309
MHAT "Vita", Cardiology Department
Sofia, Bulgaria, 1505
UMHAT "Tsaritsa Yoanna" - ISUL, Cardiology Clinic
Sofia, Bulgaria, 1527
Military Medical Academy, Clinic of Cardiology and Intesive Care
Sofia, Bulgaria, 1606
Canada, Ontario
SKDS Research Inc
New Market, Ontario, Canada, L3Y 5G8
Dr. Roger Labonté Professional Medicine Corp.
Sudbury, Ontario, Canada, P3E 3B8
Aniol Gupta MD
Toronto, Ontario, Canada, M9V 4B4
Canada, Quebec
Montréal General Hospital
Montreal, Quebec, Canada, H3G 1A4
Canada
High Desert Medical Group
Lancaster, Canada, 93534
Montreal Heart Institute
Montreal, Canada, H1T 1C8
London Road Diagnostic Clinic and Medical Centre
Ontario, Canada, N7T 4X3
Topsail Road Medical Clinic
Saint John's, Canada, A1E 2E2
Czech Republic
Vojenska Nemocnice Brno
Brno, Czech Republic, 636 00
Cardiocentrum Kladno s.r.o.
Kladno, Czech Republic, 27280
Poliklinika Modrany - Kardiologie
Praha 4, Czech Republic, 14300
Fakultní Nemocnice v Motole
Praha 5, Czech Republic, 150 06
Corintez s.r.o.
Praha 5, Czech Republic, 158 00
Centrum klinického výzkumu, s.r.o.
Príbram, Czech Republic, 26101
Nemocnice Slaný
Slaný, Czech Republic, 27401
Georgia
Tbilisi State Medical University Alexandre Aladashvili University Clinic
Tbilisi, Georgia, 0102
Amtel Hospital First Clinical LLC
Tbilisi, Georgia, 0144
Clinic "Guli"
Tbilisi, Georgia, 0144
Cardio-Reanimation Clinic LTD
Tbilisi, Georgia, 0159
Emergency Cardiology Center by Academician G. Chapidze LTD
Tbilisi, Georgia, 0159
Tbilisi Heart and Vascular Clinic LTD
Tbilisi, Georgia, 0159
Multiprofile Clinical Hospital of Tbilisi #2 LTD
Tbilisi, Georgia, 0164
Germany
Charité Campus Virchow Klinikum
Berlin, Germany, 13353
Städtische Kliniken Bielefeld
Bielefeld, Germany, 33604
Sankt Johannes-Hospital Dortmund
Dortmund, Germany, 44137
Universitätsklinikum Göttingen
Göttingen, Germany, 37099
Gemeinschaftspraxis fur Kardiologie
Heidelberg, Germany, 69115
Praxis Fur Innere Medizin Kardiologie, Pneumologic und Allergologie
Mannheim, Germany, 68165
Universitätsmedizin Mannheim
Mannheim, Germany, 68169
Israel
Barzilai Medical Center, Cardiology Dept.
Ashkelon, Israel, 78287
Assaf Harofeh Medical Centre
Be'er Ya`aqov, Israel, 70300
Shaare Zedek Medical Center
Jerusalem, Israel, 91004
Kaplan Medical Center
Rehovot, Israel, 76100
Ziv Medical Center
Safed, Israel, 13100
Tel Aviv Souraski Medical Center
Tel Aviv, Israel, 64239
Poland
MULTI-MED PLUS Sp. z o.o.
Lódz, Lodzkie, Poland, 90-553
Niepubliczny Zakład Opieki Zdrowotnej Przychodnia Zdrowia "Zadębie"
Skierniewice, Lodzkie, Poland, 96-100
KO-MED Marek Konieczny
Puławy, Lubelskie, Poland, 24-100
Specjalistyczna Praktyka Lekarska Leszek Bryniarski
Kraków, Malopolskie, Poland, 30-082
NZOZ Revita Poradnia Kardiologiczna
Kraków, Malopolskie, Poland, 31-949
Instytut Kardiologii
Warszawa, Mazowieckie, Poland, 02-637
Instytut Kardiologii
Warszawa, Mazowieckie, Poland, 04-628
NZOZ Sródmiescie Sp z o.o.
Gdynia, Pomorskie, Poland, 81-394
Pomorskie Centra Kardiologiczne S.A.
Gdansk, Poland, 80126
S.P. Specjalistyczny Szpital Zachodni im.JP II
Grodzisk, Mazowiecki, Poland, 05-825
Krakowski Szpital Specjalistyczny im.JPII
Krakow, Poland, 31-202
Synexus SCM Sp. z o.o. Oddział w Warszawie
Warszawa, Poland, 01-192
Centrum Badawcze Współczenej Terapii
Warszawa, Poland, 02-679
Slaskie Centrum Chorób Serca w Zabrzu
Zabrze, Poland, 41-800
Russian Federation
City Hospital #38 named after Semashko N.A
Pushkin, St. Petersburg, Russian Federation, 196601
Altay Regional Cardiologycal Dispensary
Barnaul, Russian Federation, 656055
"Chita State Medical Academy" Curative-Diagnostic Clinic department
Chita, Russian Federation, 672039
Sverdlovsky Regional Clinical Hospital of Wars Veterans
Ekaterinburg, Russian Federation, 620905
Municipal Institution of Healthcare "Kemerovo Cardiology Dispensary"
Kemerovo, Russian Federation, 650002
Non-state Institution of healthcare "Department hospital on station Kemerovo of OAO "Russian Railway"
Kemerovo, Russian Federation, 650056
Medical centre "Delis", LLC
Kirovsk, Russian Federation, 187342
Federal State Institution "National Research Center for Preventive Medicine"
Moscow, Russian Federation, 101990
State healthcare institution of Moscow "City Clinical hospital#15 named after O.M.Filatov"
Moscow, Russian Federation, 111539
State Healthcare institution of Moscow"Cardiology Dispensary #2"
Moscow, Russian Federation, 117556
First Moscow State Medical University I.M. Sechenov
Moscow, Russian Federation, 119991
State Budget Educational Institution of High Professional Education First Moscow State Medical University... #1, Cardiology Clinic, Hospital Therapy Department
Moscow, Russian Federation, 119991
State Budget Educational Institution of High Professional Education First Moscow State Medical University... #1, Cardiology Clinic, Hospital Therapy Department
Moscow, Russian Federation, 119992
Moscow City Clinical Hospital #51
Moscow, Russian Federation, 121309
FGU Central Clinical Hospital with Polyclinic of President Administrative Department of RF
Moscow, Russian Federation, 121359
Moscow State University of Medicine and Dentistry based on Moscow City Clinical Hospital #71
Moscow, Russian Federation, 121374
City Clinical Hospital named after S.P.Botkin
Moscow, Russian Federation, 125284
State Institution of Moscow Healthcare "City Clinical Hospital named after S.P. Botkin"
Moscow, Russian Federation, 125284
Moscow State Institution of Health "City Clinical Hospital #81"
Moscow, Russian Federation, 127644
Federal State Institution "Outpatient department #3" of President Management department of Russian Federation
Moscow, Russian Federation, 129090
State Novosibirsk Regional Clinical Hospital
Novosibirsk, Russian Federation, 630087
Regional Clinical Hospital named after N.N.Burdenko
Penza, Russian Federation, 440026
State Institution of Healthcare Perm Regional Hospital for War Veterans
Perm, Russian Federation, 614097
State Healthcare Institution "Ryazan regional clinical cardiological dispensary"
Ryazan, Russian Federation, 390026
"Clinical hospital named after S.R.Mirotvortsev"
Saratov, Russian Federation, 410054
Educational Institution of Higher Vocational Education "Smolensk State Medical Academy" on the base of Municipal Medicoprophylactic Institution "Hospital of Emergency Medical Care",
Smolensk, Russian Federation, 214000
FGU Central Clinical Hospital with Polyclinic of President Administrative Department of RF
St. Petersburg, Russian Federation, 121359
Federal State Educational Institution of High Professional Education "Military Medical Academy n.a. S.M. Kirov" of the Ministry of Defence of Russia
St. Petersburg, Russian Federation, 191124
International Medical Center "SOGAZ", LLC
St. Petersburg, Russian Federation, 191186
State Healthcare institution "Municipal Out-patient Clinic #109"
St. Petersburg, Russian Federation, 192288
Saint-Petersburg State Healthcare Institution
St. Petersburg, Russian Federation, 193144
Federal Heart, Blood and Endocrinology Centre n.a. Almazov
St. Petersburg, Russian Federation, 194156
Institution and Address: "Medical Research Institute", LLC
St. Petersburg, Russian Federation, 196084
Federal Heart, Blood and Endocrinology Centre n.a. Almazov
St. Petersburg, Russian Federation, 197341
State Institution of Healthcare "City Hospital #40 of Kurortniy administrative district
St. Petersburg, Russian Federation, 197705
Autonomous healthcare institution of Voronezh region "Voronezh regional clinic consultative and diagnostic centre"
Voronezh, Russian Federation, 394018
Municipal Institution of Healthcare "Clinical Hospital #8 of Yaroslavl"
Yaroslavl, Russian Federation, 150030
Serbia
Cardiology Clinic, Clinical Center Serbia
Belgrade, Serbia, 11000
Institute of Cardiovascular Diseases
Sremska Kamenica, Serbia, 21204
Slovakia
ALIAN, s.r.o.
Bardejov, Slovakia, 085 01
Cardioconsult, s.r.o.
Bratislava, Slovakia, 811 04
Kardiovaskulárne centrum, s.r.o.
Bratislava, Slovakia, 831 01
CARDIO D&R, s.r.o.
Košice, Slovakia, 040 22
KARDIOMED, s.r.o.
Lučenec, Slovakia, 984 01
Kardiocentrum Nitra, s.r.o.
Nitra, Slovakia, 949 01
Slovenia
University Clinic of Respiratory and Allergic Diseases Golnik
Golnik, Slovenia, 4204
University Klinicni Center Ljubljana
Ljubljana, Slovenia, 1000
General Hospital Murska Sobota
Murska Sobota, Slovenia, 9001
Ukraine
Donetsk National Medical University, Department of Internal Medicine #1 based on Department of Emergency Cardiology and Rehabilitation of Institute of Urgent and Recovery Surgery named after V. K. Gusak
Donetsk, Ukraine, 83045
Central Clinical Hospital of Ukrzaliznitsia, Cardiology department
Kharkiv, Ukraine, 61103
Kharkiv Medical Academy of Postgraduate Education, Department of cardiology and functional diagnostics based on City Clinical Hospital #8, Department of Cardiology #2
Kharkiv, Ukraine, 61176
Central polyclinic of Pechersk district, Department of cardiology
Kyiv, Ukraine, 01103
Kyiv City Clinical Hospital #1, Department of Emergency Cardiology
Kyiv, Ukraine, 02091
Kyiv city clinical hospital #5
Kyiv, Ukraine, 03115
Department of Diabetology of National Medical Academy of Postgraduate Education named after P.L.Shupyk based on Day Time Hospital of Administration of Medical Service and Rehabilitation of "ARTEM" SHC
Kyiv, Ukraine, 04050
SI "Institute of Gerontology of AMS of Ukraine"
Kyiv, Ukraine, 04114
Lviv National Medical University named after Danylo Halytsky, Department of Propaedeutics of Internal Medicine #1 based on Polyclinic Department of Municipal City Clinical Hospital #5
Lviv, Ukraine, 79044
SI Odessa Regional Cardiological Dispensary
Odessa, Ukraine, 65025
Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Patrick Yue, MD Gilead Sciences

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01425359     History of Changes
Other Study ID Numbers: GS-US-259-0133
First Posted: August 30, 2011    Key Record Dates
Results First Posted: November 4, 2014
Last Update Posted: November 4, 2014
Last Verified: October 2014
Keywords provided by Gilead Sciences:
Chronic angina
Angina pectoris
Coronary artery disease
Type 2 Diabetes Mellitus
Additional relevant MeSH terms:
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Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Angina Pectoris
Angina, Stable
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Chest Pain
Pain
Neurologic Manifestations
Signs and Symptoms
Ranolazine
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action