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

Condition(s) targeted: Angina Pectoris; Coronary Artery Disease; Type 2 Diabetes Mellitus

Intervention: Ranolazine (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Gilead Sciences

Official(s) and/or principal investigator(s):
Jay Garg, MD, Study Director, Affiliation: Gilead Sciences

This study will evaluate the safety and efficacy 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).

The purpose of this study is to evaluate if 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.

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

Primary outcome: The average weekly angina frequency over the last 6 weeks of treatment

Secondary outcome:

Average weekly frequency of sublingual nitroglycerin use over the last 6 weeks of treatment

Angina-free days over the last 6 weeks of treatment

Proportion of subjects achieving at least a 50% reduction in the average weekly angina frequency

Change from baseline in the SF-36 Mental and Physical Component Scores

PGIC scale score

Detailed description: Subjects who meet the eligibility criteria at Screening will enter a 4-to 6-week qualifying phase. The allowed concomitant antianginal medication(s) must be maintained at a stable dose throughout the study. Subjects 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. Subjects eligible to stay in the study after the qualifying phase will enter the 8-week double-blind dosing phase. Subjects will have study visits at the end of Weeks 2 and 8. Subjects will continue to document the number of angina episodes and number of SL NTG doses taken as well as a dyspnea score on a daily basis by the end of each day in their diary. In addition, subjects 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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 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 4-week single-blind placebo run-in 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 initiating the run-in period.

- Current treatment with potent inhibitors of CYP3A (eg, ketoconazole, itraconazole,

clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir)

- Current treatment with CYP3A and 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

Barzilai Medical Center, Cardiology Dept., Ashkelon 78287, Israel; Not yet recruiting
Irena Greenshtein, Phone: +972577678702, Email: irenag@barzi.health.gov.il
Bianca Fishman, Phone: +972577678091, Email: bianaf@barzi.health.gov.il
Amos Katz, MD, Principal Investigator

Assaf Harofeh Medical Centre, Be'er Ya`aqov 70300, Israel; Not yet recruiting
Roy Sagi, Phone: +97289778060, Email: roysagi@bezeqint.net
Alex Blatt, MD, Principal Investigator

Shaare Zedek Medical Center, Jerusalem 91004, Israel; Not yet recruiting
Astrid Rozanski, Phone: +97226555956, Email: astrid@szmc.org.il
Marc Klutstein, MD, Principal Investigator

Kaplan Medical Center, Rehovot 76100, Israel; Not yet recruiting
Avishag Hassid, Phone: +972502203965, Email: avishagha@clalit.org.il
Oscar Kracoff, MD, Principal Investigator

Ziv Medical Center, Safed 13100, Israel; Not yet recruiting
Luba Pritulo, Phone: +97246828482, Email: lubov.p@ziv.health.gov.il
Alon Marmor, MD, Principal Investigator

Tel Aviv Souraski Medical Center, Tel Aviv 64239, Israel; Not yet recruiting
Nurit Platner, Phone: +97236973776, Email: nuritp@tasmc.health.gov.il
David Zeltser, MD, Principal Investigator

Altay Regional Cardiologycal Dispensary, Barnaul 656055, Russian Federation; Recruiting
Galina Chumakova, MD, Phone: +7 3852 44 10 30, Email: g.a.chumakova@mail.ru
Galina Chumakova, MD, Principal Investigator

"Chita State Medical Academy" Curative-Diagnostic Clinic department, Chita 672039, Russian Federation; Recruiting
Natalya Sokolova, MD, Phone: +79242724127, Email: natalasocolova@mail.ru
Anatoly Govorin, MD, Principal Investigator

Sverdlovsky Regional Clinical Hospital of Wars Veterans, Ekaterinburg 620905, Russian Federation; Recruiting
Natalia Lepikhina, Phone: +7912 606 31 99, Email: ofdgvv@mail.ru
Mikhail Arkhipov, MD, Principal Investigator

Non-state Institution of healthcare "Department hospital on station Kemerovo of OAO "Russian Railway", Kemerovo 650056, Russian Federation; Recruiting
Anatoly Masin, MD, Phone: +79039078125, Email: anmasin@bk.ru
Anatoly Masin, MD, Principal Investigator

Medical centre "Delis", LLC, Kirovsk 187342, Russian Federation; Recruiting
Vera Eltishcheva, MD, Phone: +7 813 62 22772, Email: vera-eltischeva@rambler.ru
Vera Eltishcheva, MD, Principal Investigator

First Moscow State Medical University I.M. Sechenov, Moscow 119991, Russian Federation; Recruiting
Artem Doletskiy, Phone: +74992480603, Email: artdoletsky@mail.ru
Denis Andreev, MD, Principal Investigator

State healthcare institution of Moscow "City Clinical hospital#15 named after O.M.Filatov", Moscow 111539, Russian Federation; Recruiting
Elena Luchinkina, Phone: +79261750756, Email: eluchinkina@gmail.com
Ivan Gordeev, MD, Principal Investigator

Moscow State University of Medicine and Dentistry based on Moscow City Clinical Hospital #71, Moscow 121374, Russian Federation; Recruiting
Tatyana Ivanova, MD, Phone: +74997376232, Email: tbiva@mail.ru
Tatyana Ivanova, MD, Principal Investigator

State Healthcare institution of Moscow"Cardiology Dispensary #2", Moscow 117556, Russian Federation; Recruiting
Alexander Vozzhaev, Phone: +79104263280, Email: alex.vozzhaev@gmail.com
Sergey Fitilev, MD, Principal Investigator

State Novosibirsk Regional Clinical Hospital, Novosibirsk 630087, Russian Federation; Recruiting
Irina Ivanova, Phone: +7 383 315 96 93, Email: Ivanova.irina.v@mail.ru
Sergey Ivanov, MD, Principal Investigator

State Healthcare Institution "Ryazan regional clinical cardiological dispensary", Ryazan 390026, Russian Federation; Recruiting
Natalia Nikulina, Phone: 7 910 906 84 54, Email: natalia.nikulina@mail.ru
Sergey Yakushin, MD, Principal Investigator

State Healthcare institution "Municipal Out-patient Clinic #109", St. Petersburg 192288, Russian Federation; Recruiting
Farid Tumarov, Phone: 7 812 366 55 32, Email: tumafa@mail.ru
Victor Kostenko, MD, Principal Investigator

"Medical Research Institute", LLC, St. Petersburg 196084, Russian Federation; Recruiting
Zhanna Paltsman, MD, Phone: +7812 369 24 86, Email: zhannapaltsman@yandex.ru
Zhanna Paltsman, MD, Principal Investigator

Municipal Institution of Healthcare "Clinical Hospital #8 of Yaroslavl", Yaroslavl 150030, Russian Federation; Recruiting
Alexander Malygin, MD, Phone: +7(4852)447912, Email: doc_mal@rambler.ru
Alexander Malygin, MD, Principal Investigator

Cardiology and Medicine Clinic, Little Rock, Arkansas 72204, United States; Recruiting
Tina Green, Phone: 501-664-0941, Email: cmcresearch1@gmail.com
Joe Hargrove, MD, Principal Investigator

Spectrum Clinical Research Institute, Inc, Moreno Valley, California 92553, United States; Recruiting
Alfred Serrato, Phone: 951-247-3080, Email: aserrato@scrinstitute.com
George Ponce, MD, Principal Investigator

Sacramento Heart and Vascular Medical Associates, Sacramento, California 95825, United States; Recruiting
Leslie Sears, Phone: 916-830-2084, Email: lsears@sacheart.com
Daniel VanHamersveld, MD, Principal Investigator

HealthwoRx, Hollywood, Florida 33021, United States; Recruiting
Maria Mejia, Phone: 954-986-3067, Email: mmejiagomez@mitral.com
Adam Splaver, MD, Principal Investigator

Jacksonville Heart Center, Jacksonville, Florida 32207, United States; Recruiting
Nancy Ebreo, Phone: 904-398-0125, Email: nwilliams@jaxheart.com
Marc Litt, MD, Principal Investigator

Clinical Research of Central Florida, Winter Haven, Florida 33880, United States; Recruiting
Vickie Boelman, Phone: 863-677-8648, Email: vboelman@clinicalresearchcf.com
Richard Giusti, MD, Principal Investigator

Masters of Clinical Research, Inc., Augusta, Georgia 30909, United States; Recruiting
Yeini Thompson, Phone: 706-210-8890, Email: mcr-research@comcast.net
Amy Sprague, MD, Principal Investigator

Columbus Cardiology Associates, PC, Columbus, Georgia 31909, United States; Recruiting
Kindal Klein, Phone: 706-243-2320, Email: kklein@ccaheart.com
Alonzo Jones, PI, Principal Investigator

Central Cardiology Associates, Elizabethtown, Kentucky 42701, United States; Recruiting
Amy Steward, Phone: 270-765-5921, Email: amys@centralcardiology.com
Krishnan Challappa, MD, Principal Investigator

Clinical Trials Management, LLC, Mandeville, Louisiana 70471, United States; Recruiting
Sandi Bailey, Phone: 985-727-1781, Email: sbailey@clinicaltrialsmgt.com
Dale Presser, MD, Principal Investigator

Endeavor Medical Research, PLC, Alpena, Michigan 49707, United States; Recruiting
Sandra Keavey, Phone: 989-356-0141, Email: skeavey@gmail.com
Abraham Salacata, MD, Principal Investigator

Cross Country Cardiology, Edgewater, New Jersey 07020, United States; Recruiting
Brian Bechtold, Phone: 201-941-8100, Email: bechtoldpa@yahoo.com
Yaron Bareket, MD, Principal Investigator

Dr. Roger Labonté Professional Medicine Corp., Sudbury, Ontario P3E 3B8, Canada; Recruiting
Cynthia Dewar, Phone: 1 (705) 522-7346, Email: cdewar@bellnet.ca
Roger Labonté, MD, Principal Investigator

City Hospital #38 named after Semashko N.A, Pushkin, St. Petersburg 196601, Russian Federation; Recruiting
Elena Ilyaynen, Phone: +79119667859, Email: ilyaynen@mail.ru
Konstantin Zrazhevsky, MD, Principal Investigator

Heart and Vascular Center of West TN, Jackson, Tennessee 38305, United States; Recruiting
Ashley Childs, Phone: 731-668-2620, Email: achilds@deltamedicus.com
Elie Hage-Korban, MD, Principal Investigator

Med-Tech Research, Houston, Texas 77024, United States; Recruiting
Chandra Garret, Phone: 713-465-3535, Email: cgarret@chchouston.com
Salah El-Hafi, MD, Principal Investigator

Humble Cardiology Associates, Humble, Texas 77338, United States; Recruiting
Sheila Tackett, Phone: 281-446-5386, Email: drrevana@aol.com
Madaiah Revana, MD, Principal Investigator

Starting date: September 2011
Last updated: November 28, 2011