NCT01425359

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.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
949

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Sep 2011

Shorter than P25 for phase_4

Geographic Reach
13 countries

132 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 24, 2011

Completed
6 days until next milestone

First Posted

Study publicly available on registry

August 30, 2011

Completed
2 days until next milestone

Study Start

First participant enrolled

September 1, 2011

Completed
1.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2012

Completed
2.1 years until next milestone

Results Posted

Study results publicly available

November 4, 2014

Completed
Last Updated

November 4, 2014

Status Verified

October 1, 2014

Enrollment Period

1.1 years

First QC Date

August 24, 2011

Results QC Date

October 20, 2014

Last Update Submit

October 30, 2014

Conditions

Keywords

Chronic anginaAngina pectorisCoronary artery diseaseType 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

  • Average Weekly Angina Frequency Over the Last 6 Weeks of Treatment

    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.

    6 weeks

Secondary Outcomes (5)

  • Average Weekly Frequency of Sublingual Nitroglycerin Use Over the Last 6 Weeks of Treatment

    6 weeks

  • Percentage of Weeks Participants Achieved at Least a 50% Reduction in Angina Frequency

    6 weeks

  • Percentage of the Last 6 Weeks on Treatment During Which the Angina Frequency Was ≤ 50% of the Baseline Average Weekly Angina Frequency

    6 weeks

  • Change From Baseline in the Short-Form 36® (SF-36) Mental and Physical Component Scores

    Up to 8 weeks

  • Patient's Global Impression of Change (PGIC) Scale Score

    8 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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

Ranolazine

EXPERIMENTAL

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: RanolazineDrug: Ranolazine placebo

Interventions

Also known as: Ranexa®
Ranolazine
PlaceboRanolazine

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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:
  • Angiographic evidence of ≥ 50% stenosis of one or more major coronary arteries
  • History of myocardial infarction (MI) documented by positive myocardial muscle creatine kinase (CK-MB) enzymes, troponins, or electrocardiogram (ECG) changes
  • 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.

You may not qualify if:

  • 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)
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (135)

Cardiology and Medicine Clinic

Little Rock, Arkansas, 72204, United States

Location

Merced Heart Associates

Merced, California, 95340, United States

Location

Spectrum Clinical Research Institute, Inc

Moreno Valley, California, 92553, United States

Location

Sacramento Heart and Vascular Research Center

Sacramento, California, 95825, United States

Location

South Florida Research Solutions, LLC

Hollywood, Florida, 33021, United States

Location

Baptist Heart Specialist

Jacksonville, Florida, 32207, United States

Location

Clinical Research of Central Florida

Winter Haven, Florida, 33880, United States

Location

Masters of Clinical Research, Inc.

Augusta, Georgia, 30909, United States

Location

Columbus Cardiology Associates

Columbus, Georgia, 31909, United States

Location

Central Cardiology Associates

Elizabethtown, Kentucky, 42701, United States

Location

Research Integrity, LLC

Owensboro, Kentucky, 42303, United States

Location

Alexandria Cardiology Clinic

Alexandria, Louisiana, 71301, United States

Location

Clinical Trials Management, LLC

Mandeville, Louisiana, 70471, United States

Location

Endeavor Medical Research, PLC

Alpena, Michigan, 49707, United States

Location

Minneapolis Heart Institute Foundation

Minneapolis, Minnesota, 55407, United States

Location

Cross Country Cardiology

Edgewater, New Jersey, 07020, United States

Location

Kore CV Research

Jackson, Tennessee, 38305, United States

Location

Wellmont Cardiovascular Associates Heart Institute

Johnson City, Tennessee, 37604, United States

Location

Med-Tech Research

Houston, Texas, 77024, United States

Location

Humble Cardiology Associates

Humble, Texas, 77338, United States

Location

State Institution "Gomel regional clinical hospital"

Homyel, 246029, Belarus

Location

State Inst Rep Scientific and Practical center

Minsk, 220036, Belarus

Location

Diagnostic Consultative Center, Ascendent Cardiological Out-Patient Office

Sofia, 1202, Bulgaria

Location

MHAT "Tsar Boris III"

Sofia, 1233, Bulgaria

Location

National Cardiology Center, Cardiology Clinic - III

Sofia, 1309, Bulgaria

Location

MHAT "Vita", Cardiology Department

Sofia, 1505, Bulgaria

Location

UMHAT "Tsaritsa Yoanna" - ISUL, Cardiology Clinic

Sofia, 1527, Bulgaria

Location

Military Medical Academy, Clinic of Cardiology and Intesive Care

Sofia, 1606, Bulgaria

Location

Dr. Roger Labonté Professional Medicine Corp.

Greater Sudbury, Ontario, P3E 3B8, Canada

Location

SKDS Research Inc

Newmarket, Ontario, L3Y 5G8, Canada

Location

Aniol Gupta MD

Toronto, Ontario, M9V 4B4, Canada

Location

Montréal General Hospital

Montreal, Quebec, H3G 1A4, Canada

Location

High Desert Medical Group

Lancaster, 93534, Canada

Location

Montreal Heart Institute

Montreal, H1T 1C8, Canada

Location

London Road Diagnostic Clinic and Medical Centre

Ontario, N7T 4X3, Canada

Location

Topsail Road Medical Clinic

St. John's, A1E 2E2, Canada

Location

Vojenska Nemocnice Brno

Brno, 636 00, Czechia

Location

Cardiocentrum Kladno s.r.o.

Kladno, 27280, Czechia

Location

Poliklinika Modrany - Kardiologie

Prague, 14300, Czechia

Location

Fakultní Nemocnice v Motole

Prague, 150 06, Czechia

Location

Corintez s.r.o.

Prague, 158 00, Czechia

Location

Centrum klinického výzkumu, s.r.o.

Príbram, 26101, Czechia

Location

Nemocnice Slaný

Slaný, 27401, Czechia

Location

Tbilisi State Medical University Alexandre Aladashvili University Clinic

Tbilisi, 0102, Georgia

Location

Amtel Hospital First Clinical LLC

Tbilisi, 0144, Georgia

Location

Clinic "Guli"

Tbilisi, 0144, Georgia

Location

Cardio-Reanimation Clinic LTD

Tbilisi, 0159, Georgia

Location

Emergency Cardiology Center by Academician G. Chapidze LTD

Tbilisi, 0159, Georgia

Location

Tbilisi Heart and Vascular Clinic LTD

Tbilisi, 0159, Georgia

Location

Multiprofile Clinical Hospital of Tbilisi #2 LTD

Tbilisi, 0164, Georgia

Location

Charité Campus Virchow Klinikum

Berlin, 13353, Germany

Location

Städtische Kliniken Bielefeld

Bielefeld, 33604, Germany

Location

Sankt Johannes-Hospital Dortmund

Dortmund, 44137, Germany

Location

Universitätsklinikum Göttingen

Göttingen, 37099, Germany

Location

Gemeinschaftspraxis fur Kardiologie

Heidelberg, 69115, Germany

Location

Praxis Fur Innere Medizin Kardiologie, Pneumologic und Allergologie

Mannheim, 68165, Germany

Location

Universitätsmedizin Mannheim

Mannheim, 68169, Germany

Location

Barzilai Medical Center, Cardiology Dept.

Ashkelon, 78287, Israel

Location

Assaf Harofeh Medical Centre

Be’er Ya‘aqov, 70300, Israel

Location

Shaare Zedek Medical Center

Jerusalem, 91004, Israel

Location

Kaplan Medical Center

Rehovot, 76100, Israel

Location

Ziv Medical Center

Safed, 13100, Israel

Location

Tel Aviv Souraski Medical Center

Tel Aviv, 64239, Israel

Location

Specjalistyczna Praktyka Lekarska Leszek Bryniarski

Krakow, Lesser Poland Voivodeship, 30-082, Poland

Location

NZOZ Revita Poradnia Kardiologiczna

Krakow, Lesser Poland Voivodeship, 31-949, Poland

Location

KO-MED Marek Konieczny

Puławy, Lublin Voivodeship, 24-100, Poland

Location

Instytut Kardiologii

Warsaw, Masovian Voivodeship, 02-637, Poland

Location

Instytut Kardiologii

Warsaw, Masovian Voivodeship, 04-628, Poland

Location

NZOZ Sródmiescie Sp z o.o.

Gdynia, Pomeranian Voivodeship, 81-394, Poland

Location

Pomorskie Centra Kardiologiczne S.A.

Gdansk, 80126, Poland

Location

S.P. Specjalistyczny Szpital Zachodni im.JP II

Grodzisk Mazowiecki, 05-825, Poland

Location

Krakowski Szpital Specjalistyczny im.JPII

Krakow, 31-202, Poland

Location

Synexus SCM Sp. z o.o. Oddział w Warszawie

Warsaw, 01-192, Poland

Location

Centrum Badawcze Współczenej Terapii

Warsaw, 02-679, Poland

Location

Slaskie Centrum Chorób Serca w Zabrzu

Zabrze, 41-800, Poland

Location

MULTI-MED PLUS Sp. z o.o.

Lódz, Łódź Voivodeship, 90-553, Poland

Location

Niepubliczny Zakład Opieki Zdrowotnej Przychodnia Zdrowia "Zadębie"

Skierniewice, Łódź Voivodeship, 96-100, Poland

Location

City Hospital #38 named after Semashko N.A

Pushkin, Sankt-Peterburg, 196601, Russia

Location

Altay Regional Cardiologycal Dispensary

Barnaul, 656055, Russia

Location

"Chita State Medical Academy" Curative-Diagnostic Clinic department

Chita, 672039, Russia

Location

Municipal Institution of Healthcare "Kemerovo Cardiology Dispensary"

Kemerovo, 650002, Russia

Location

Non-state Institution of healthcare "Department hospital on station Kemerovo of OAO "Russian Railway"

Kemerovo, 650056, Russia

Location

Medical centre "Delis", LLC

Kirovsk, 187342, Russia

Location

Federal State Institution "National Research Center for Preventive Medicine"

Moscow, 101990, Russia

Location

State healthcare institution of Moscow "City Clinical hospital#15 named after O.M.Filatov"

Moscow, 111539, Russia

Location

State Healthcare institution of Moscow"Cardiology Dispensary #2"

Moscow, 117556, Russia

Location

First Moscow State Medical University I.M. Sechenov

Moscow, 119991, Russia

Location

State Budget Educational Institution of High Professional Education First Moscow State Medical University... #1, Cardiology Clinic, Hospital Therapy Department

Moscow, 119991, Russia

Location

State Budget Educational Institution of High Professional Education First Moscow State Medical University... #1, Cardiology Clinic, Hospital Therapy Department

Moscow, 119992, Russia

Location

Moscow City Clinical Hospital #51

Moscow, 121309, Russia

Location

FGU Central Clinical Hospital with Polyclinic of President Administrative Department of RF

Moscow, 121359, Russia

Location

Moscow State University of Medicine and Dentistry based on Moscow City Clinical Hospital #71

Moscow, 121374, Russia

Location

City Clinical Hospital named after S.P.Botkin

Moscow, 125284, Russia

Location

State Institution of Moscow Healthcare "City Clinical Hospital named after S.P. Botkin"

Moscow, 125284, Russia

Location

Moscow State Institution of Health "City Clinical Hospital #81"

Moscow, 127644, Russia

Location

Federal State Institution "Outpatient department #3" of President Management department of Russian Federation

Moscow, 129090, Russia

Location

State Novosibirsk Regional Clinical Hospital

Novosibirsk, 630087, Russia

Location

Regional Clinical Hospital named after N.N.Burdenko

Penza, 440026, Russia

Location

State Institution of Healthcare Perm Regional Hospital for War Veterans

Perm, 614097, Russia

Location

State Healthcare Institution "Ryazan regional clinical cardiological dispensary"

Ryazan, 390026, Russia

Location

FGU Central Clinical Hospital with Polyclinic of President Administrative Department of RF

Saint Petersburg, 121359, Russia

Location

Federal State Educational Institution of High Professional Education "Military Medical Academy n.a. S.M. Kirov" of the Ministry of Defence of Russia

Saint Petersburg, 191124, Russia

Location

International Medical Center "SOGAZ", LLC

Saint Petersburg, 191186, Russia

Location

State Healthcare institution "Municipal Out-patient Clinic #109"

Saint Petersburg, 192288, Russia

Location

Saint-Petersburg State Healthcare Institution

Saint Petersburg, 193144, Russia

Location

Federal Heart, Blood and Endocrinology Centre n.a. Almazov

Saint Petersburg, 194156, Russia

Location

Institution and Address: "Medical Research Institute", LLC

Saint Petersburg, 196084, Russia

Location

Federal Heart, Blood and Endocrinology Centre n.a. Almazov

Saint Petersburg, 197341, Russia

Location

State Institution of Healthcare "City Hospital #40 of Kurortniy administrative district

Saint Petersburg, 197705, Russia

Location

"Clinical hospital named after S.R.Mirotvortsev"

Saratov, 410054, Russia

Location

Educational Institution of Higher Vocational Education "Smolensk State Medical Academy" on the base of Municipal Medicoprophylactic Institution "Hospital of Emergency Medical Care",

Smolensk, 214000, Russia

Location

Autonomous healthcare institution of Voronezh region "Voronezh regional clinic consultative and diagnostic centre"

Voronezh, 394018, Russia

Location

Municipal Institution of Healthcare "Clinical Hospital #8 of Yaroslavl"

Yaroslavl, 150030, Russia

Location

Sverdlovsky Regional Clinical Hospital of Wars Veterans

Yekaterinburg, 620905, Russia

Location

Cardiology Clinic, Clinical Center Serbia

Belgrade, 11000, Serbia

Location

Institute of Cardiovascular Diseases

Kamenitz, 21204, Serbia

Location

ALIAN, s.r.o.

Bardejov, 085 01, Slovakia

Location

Cardioconsult, s.r.o.

Bratislava, 811 04, Slovakia

Location

Kardiovaskulárne centrum, s.r.o.

Bratislava, 831 01, Slovakia

Location

CARDIO D&R, s.r.o.

Košice, 040 22, Slovakia

Location

KARDIOMED, s.r.o.

Lučenec, 984 01, Slovakia

Location

Kardiocentrum Nitra, s.r.o.

Nitra, 949 01, Slovakia

Location

University Clinic of Respiratory and Allergic Diseases Golnik

Golnik, 4204, Slovenia

Location

University Klinicni Center Ljubljana

Ljubljana, 1000, Slovenia

Location

General Hospital Murska Sobota

Murska Sobota, 9001, Slovenia

Location

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, 83045, Ukraine

Location

Central Clinical Hospital of Ukrzaliznitsia, Cardiology department

Kharkiv, 61103, Ukraine

Location

Kharkiv Medical Academy of Postgraduate Education, Department of cardiology and functional diagnostics based on City Clinical Hospital #8, Department of Cardiology #2

Kharkiv, 61176, Ukraine

Location

Central polyclinic of Pechersk district, Department of cardiology

Kyiv, 01103, Ukraine

Location

Kyiv City Clinical Hospital #1, Department of Emergency Cardiology

Kyiv, 02091, Ukraine

Location

Kyiv city clinical hospital #5

Kyiv, 03115, Ukraine

Location

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, 04050, Ukraine

Location

SI "Institute of Gerontology of AMS of Ukraine"

Kyiv, 04114, Ukraine

Location

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, 79044, Ukraine

Location

SI Odessa Regional Cardiological Dispensary

Odesa, 65025, Ukraine

Location

Related Publications (3)

  • Arnold SV, Kosiborod M, Li Y, Jones PG, Yue P, Belardinelli L, Spertus JA. Comparison of the Seattle Angina Questionnaire With Daily Angina Diary in the TERISA Clinical Trial. Circ Cardiovasc Qual Outcomes. 2014 Nov;7(6):844-50. doi: 10.1161/CIRCOUTCOMES.113.000752. Epub 2014 Sep 23.

  • Roubinian NH, Escobar GJ, Liu V, Gardner MN, Carson JL, Kleinman SH, Murphy EL; NHLBI Recipient Epidemiology and Donor Evaluation Study (REDS-III). Decreased red blood cell use and mortality in hospitalized patients. JAMA Intern Med. 2014 Aug;174(8):1405-7. doi: 10.1001/jamainternmed.2014.2889. No abstract available.

  • Kosiborod M, Arnold SV, Spertus JA, McGuire DK, Li Y, Yue P, Ben-Yehuda O, Katz A, Jones PG, Olmsted A, Belardinelli L, Chaitman BR. Evaluation of ranolazine in patients with type 2 diabetes mellitus and chronic stable angina: results from the TERISA randomized clinical trial (Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina). J Am Coll Cardiol. 2013 May 21;61(20):2038-45. doi: 10.1016/j.jacc.2013.02.011. Epub 2013 Mar 10.

MeSH Terms

Conditions

Angina PectorisCoronary Artery DiseaseDiabetes Mellitus, Type 2

Interventions

Ranolazine

Condition Hierarchy (Ancestors)

Myocardial IschemiaHeart DiseasesCardiovascular DiseasesVascular DiseasesChest PainPainNeurologic ManifestationsSigns and SymptomsPathological Conditions, Signs and SymptomsCoronary DiseaseArteriosclerosisArterial Occlusive DiseasesDiabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Intervention Hierarchy (Ancestors)

AcetanilidesAnilidesAmidesOrganic ChemicalsAniline CompoundsAminesPiperazinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Results Point of Contact

Title
Clinical Trial Disclosures
Organization
Gilead Sciences, Inc.

Study Officials

  • Patrick Yue, MD

    Gilead Sciences

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

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
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 24, 2011

First Posted

August 30, 2011

Study Start

September 1, 2011

Primary Completion

October 1, 2012

Study Completion

October 1, 2012

Last Updated

November 4, 2014

Results First Posted

November 4, 2014

Record last verified: 2014-10

Locations