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

Coronary Artery Disease Clinical Trial

— TERISA  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01425359
• Other study ID #: GS-US-259-0133
• Status: Completed
• Phase: Phase 4
• First received: August 24, 2011
• Last updated: October 30, 2014
• Start date: September 2011
• Est. completion date: October 2012

Study information

• Verified date: October 2014
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review BoardCanada: Health CanadaCanada: Ethics Review CommitteeBelarus: Ministry of HealthCzech Republic: Ethics CommitteeCzech Republic: State Institute for Drug ControlGeorgia: Ministry of HealthGermany: Federal Institute for Drugs and Medical DevicesGermany: Ethics CommissionIsrael: Ethics CommissionIsrael: Ministry of HealthPoland: Ethics CommitteePoland: The Central Register of Clinical TrialsRussia: Ethics CommitteeRussia: Ministry of Health of the Russian FederationSerbia and Montenegro: Agency for Drugs and Medicinal DevicesSerbia: Ethics CommitteeUkraine: Ethics CommitteeUkraine: Ministry of HealthRomania: Ethics CommitteeRomania: National Medicines AgencySlovak Republic: Ethics CommitteeSlovakia: State Institute for Drug ControlSlovenia: Agency for Medicinal Products - Ministry of HealthSlovenia: Ethics CommitteeBulgaria: Bulgarian Drug AgencyBulgaria: Ethics committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 949
• Est. completion date: October 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Angina Pectoris
• Angina, Stable
• Coronary Artery Disease
• Coronary Disease
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Myocardial Ischemia
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Ranolazine

• Ranolazine placebo

Locations

Country	Name	City	State
Belarus	State Institution "Gomel regional clinical hospital"	Gomel
Belarus	State Inst Rep Scientific and Practical center	Minsk
Bulgaria	Diagnostic Consultative Center, Ascendent Cardiological Out-Patient Office	Sofia
Bulgaria	MHAT "Tsar Boris III"	Sofia
Bulgaria	MHAT "Vita", Cardiology Department	Sofia
Bulgaria	Military Medical Academy, Clinic of Cardiology and Intesive Care	Sofia
Bulgaria	National Cardiology Center, Cardiology Clinic - III	Sofia
Bulgaria	UMHAT "Tsaritsa Yoanna" - ISUL, Cardiology Clinic	Sofia
Canada	High Desert Medical Group	Lancaster
Canada	Montréal General Hospital	Montreal	Quebec
Canada	Montreal Heart Institute	Montreal
Canada	SKDS Research Inc	New Market	Ontario
Canada	London Road Diagnostic Clinic and Medical Centre	Ontario
Canada	Topsail Road Medical Clinic	Saint John's
Canada	Dr. Roger Labonté Professional Medicine Corp.	Sudbury	Ontario
Canada	Aniol Gupta MD	Toronto	Ontario
Czech Republic	Vojenska Nemocnice Brno	Brno
Czech Republic	Cardiocentrum Kladno s.r.o.	Kladno
Czech Republic	Poliklinika Modrany - Kardiologie	Praha 4
Czech Republic	Corintez s.r.o.	Praha 5
Czech Republic	Fakultní Nemocnice v Motole	Praha 5
Czech Republic	Centrum klinického výzkumu, s.r.o.	Príbram
Czech Republic	Nemocnice Slaný	Slaný
Georgia	Amtel Hospital First Clinical LLC	Tbilisi
Georgia	Cardio-Reanimation Clinic LTD	Tbilisi
Georgia	Clinic "Guli"	Tbilisi
Georgia	Emergency Cardiology Center by Academician G. Chapidze LTD	Tbilisi
Georgia	Multiprofile Clinical Hospital of Tbilisi #2 LTD	Tbilisi
Georgia	Tbilisi Heart and Vascular Clinic LTD	Tbilisi
Georgia	Tbilisi State Medical University Alexandre Aladashvili University Clinic	Tbilisi
Germany	Charité Campus Virchow Klinikum	Berlin
Germany	Städtische Kliniken Bielefeld	Bielefeld
Germany	Sankt Johannes-Hospital Dortmund	Dortmund
Germany	Universitätsklinikum Göttingen	Göttingen
Germany	Gemeinschaftspraxis fur Kardiologie	Heidelberg
Germany	Praxis Fur Innere Medizin Kardiologie, Pneumologic und Allergologie	Mannheim
Germany	Universitätsmedizin Mannheim	Mannheim
Israel	Barzilai Medical Center, Cardiology Dept.	Ashkelon
Israel	Assaf Harofeh Medical Centre	Be'er Ya`aqov
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Kaplan Medical Center	Rehovot
Israel	Ziv Medical Center	Safed
Israel	Tel Aviv Souraski Medical Center	Tel Aviv
Poland	Pomorskie Centra Kardiologiczne S.A.	Gdansk
Poland	NZOZ Sródmiescie Sp z o.o.	Gdynia	Pomorskie
Poland	S.P. Specjalistyczny Szpital Zachodni im.JP II	Grodzisk, Mazowiecki
Poland	Krakowski Szpital Specjalistyczny im.JPII	Krakow
Poland	NZOZ Revita Poradnia Kardiologiczna	Kraków	Malopolskie
Poland	Specjalistyczna Praktyka Lekarska Leszek Bryniarski	Kraków	Malopolskie
Poland	MULTI-MED PLUS Sp. z o.o.	Lódz	Lodzkie
Poland	KO-MED Marek Konieczny	Pulawy	Lubelskie
Poland	Niepubliczny Zaklad Opieki Zdrowotnej Przychodnia Zdrowia "Zadebie"	Skierniewice	Lodzkie
Poland	Centrum Badawcze Wspólczenej Terapii	Warszawa
Poland	Instytut Kardiologii	Warszawa	Mazowieckie
Poland	Instytut Kardiologii	Warszawa	Mazowieckie
Poland	Synexus SCM Sp. z o.o. Oddzial w Warszawie	Warszawa
Poland	Slaskie Centrum Chorób Serca w Zabrzu	Zabrze
Russian Federation	Altay Regional Cardiologycal Dispensary	Barnaul
Russian Federation	"Chita State Medical Academy" Curative-Diagnostic Clinic department	Chita
Russian Federation	Sverdlovsky Regional Clinical Hospital of Wars Veterans	Ekaterinburg
Russian Federation	Municipal Institution of Healthcare "Kemerovo Cardiology Dispensary"	Kemerovo
Russian Federation	Non-state Institution of healthcare "Department hospital on station Kemerovo of OAO "Russian Railway"	Kemerovo
Russian Federation	Medical centre "Delis", LLC	Kirovsk
Russian Federation	City Clinical Hospital named after S.P.Botkin	Moscow
Russian Federation	Federal State Institution "National Research Center for Preventive Medicine"	Moscow
Russian Federation	Federal State Institution "Outpatient department #3" of President Management department of Russian Federation	Moscow
Russian Federation	FGU Central Clinical Hospital with Polyclinic of President Administrative Department of RF	Moscow
Russian Federation	First Moscow State Medical University I.M. Sechenov	Moscow
Russian Federation	Moscow City Clinical Hospital #51	Moscow
Russian Federation	Moscow State Institution of Health "City Clinical Hospital #81"	Moscow
Russian Federation	Moscow State University of Medicine and Dentistry based on Moscow City Clinical Hospital #71	Moscow
Russian Federation	State Budget Educational Institution of High Professional Education First Moscow State Medical University... #1, Cardiology Clinic, Hospital Therapy Department	Moscow
Russian Federation	State Budget Educational Institution of High Professional Education First Moscow State Medical University... #1, Cardiology Clinic, Hospital Therapy Department	Moscow
Russian Federation	State healthcare institution of Moscow "City Clinical hospital#15 named after O.M.Filatov"	Moscow
Russian Federation	State Healthcare institution of Moscow"Cardiology Dispensary #2"	Moscow
Russian Federation	State Institution of Moscow Healthcare "City Clinical Hospital named after S.P. Botkin"	Moscow
Russian Federation	State Novosibirsk Regional Clinical Hospital	Novosibirsk
Russian Federation	Regional Clinical Hospital named after N.N.Burdenko	Penza
Russian Federation	State Institution of Healthcare Perm Regional Hospital for War Veterans	Perm
Russian Federation	City Hospital #38 named after Semashko N.A	Pushkin	St. Petersburg
Russian Federation	State Healthcare Institution "Ryazan regional clinical cardiological dispensary"	Ryazan
Russian Federation	"Clinical hospital named after S.R.Mirotvortsev"	Saratov
Russian Federation	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	Federal Heart, Blood and Endocrinology Centre n.a. Almazov	St. Petersburg
Russian Federation	Federal Heart, Blood and Endocrinology Centre n.a. Almazov	St. Petersburg
Russian Federation	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	FGU Central Clinical Hospital with Polyclinic of President Administrative Department of RF	St. Petersburg
Russian Federation	Institution and Address: "Medical Research Institute", LLC	St. Petersburg
Russian Federation	International Medical Center "SOGAZ", LLC	St. Petersburg
Russian Federation	Saint-Petersburg State Healthcare Institution	St. Petersburg
Russian Federation	State Healthcare institution "Municipal Out-patient Clinic #109"	St. Petersburg
Russian Federation	State Institution of Healthcare "City Hospital #40 of Kurortniy administrative district	St. Petersburg
Russian Federation	Autonomous healthcare institution of Voronezh region "Voronezh regional clinic consultative and diagnostic centre"	Voronezh
Russian Federation	Municipal Institution of Healthcare "Clinical Hospital #8 of Yaroslavl"	Yaroslavl
Serbia	Cardiology Clinic, Clinical Center Serbia	Belgrade
Serbia	Institute of Cardiovascular Diseases	Sremska Kamenica
Slovakia	ALIAN, s.r.o.	Bardejov
Slovakia	Cardioconsult, s.r.o.	Bratislava
Slovakia	Kardiovaskulárne centrum, s.r.o.	Bratislava
Slovakia	CARDIO D&R, s.r.o.	Košice
Slovakia	KARDIOMED, s.r.o.	Lucenec
Slovakia	Kardiocentrum Nitra, s.r.o.	Nitra
Slovenia	University Clinic of Respiratory and Allergic Diseases Golnik	Golnik
Slovenia	University Klinicni Center Ljubljana	Ljubljana
Slovenia	General Hospital Murska Sobota	Murska Sobota
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	Central Clinical Hospital of Ukrzaliznitsia, Cardiology department	Kharkiv
Ukraine	Kharkiv Medical Academy of Postgraduate Education, Department of cardiology and functional diagnostics based on City Clinical Hospital #8, Department of Cardiology #2	Kharkiv
Ukraine	Central polyclinic of Pechersk district, Department of cardiology	Kyiv
Ukraine	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	Kyiv City Clinical Hospital #1, Department of Emergency Cardiology	Kyiv
Ukraine	Kyiv city clinical hospital #5	Kyiv
Ukraine	SI "Institute of Gerontology of AMS of Ukraine"	Kyiv
Ukraine	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	SI Odessa Regional Cardiological Dispensary	Odessa
United States	Alexandria Cardiology Clinic	Alexandria	Louisiana
United States	Endeavor Medical Research, PLC	Alpena	Michigan
United States	Masters of Clinical Research, Inc.	Augusta	Georgia
United States	Columbus Cardiology Associates	Columbus	Georgia
United States	Cross Country Cardiology	Edgewater	New Jersey
United States	Central Cardiology Associates	Elizabethtown	Kentucky
United States	South Florida Research Solutions, LLC	Hollywood	Florida
United States	Med-Tech Research	Houston	Texas
United States	Humble Cardiology Associates	Humble	Texas
United States	Kore CV Research	Jackson	Tennessee
United States	Baptist Heart Specialist	Jacksonville	Florida
United States	Wellmont Cardiovascular Associates Heart Institute	Johnson City	Tennessee
United States	Cardiology and Medicine Clinic	Little Rock	Arkansas
United States	Clinical Trials Management, LLC	Mandeville	Louisiana
United States	Merced Heart Associates	Merced	California
United States	Minneapolis Heart Institute Foundation	Minneapolis	Minnesota
United States	Spectrum Clinical Research Institute, Inc	Moreno Valley	California
United States	Research Integrity, LLC	Owensboro	Kentucky
United States	Sacramento Heart and Vascular Research Center	Sacramento	California
United States	Clinical Research of Central Florida	Winter Haven	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Belarus,  Bulgaria,  Canada,  Czech Republic,  Georgia,  Germany,  Israel,  Poland,  Russian Federation,  Serbia,  Slovakia,  Slovenia,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Average Weekly Frequency of Sublingual Nitroglycerin Use Over the Last 6 Weeks of Treatment	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.	6 weeks	No
Secondary	Percentage of Weeks Participants Achieved at Least a 50% Reduction in Angina Frequency	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.	6 weeks	No
Secondary	Percentage of the Last 6 Weeks on Treatment During Which the Angina Frequency Was = 50% of the Baseline Average Weekly Angina Frequency		6 weeks	No
Secondary	Change From Baseline in the Short-Form 36® (SF-36) Mental and Physical Component Scores	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.	Up to 8 weeks	No
Secondary	Patient's Global Impression of Change (PGIC) Scale Score	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).	8 weeks	No