Ranolazine Monotherapy in Subjects With Type 2 Diabetes Mellitus

NCT ID: NCT01472185

Last Updated: 2014-10-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 465 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2013-10-31

Brief Summary

This is a randomized, double-blind, placebo-controlled, parallel-group, multi-center study to determine the effect of ranolazine when given as monotherapy on glycemic control in subjects with type 2 diabetes mellitus (T2DM) who were inadequately controlled with diet and exercise alone and who are treatment naive to antihyperglycemic therapy or have not received antihyperglycemic therapy in the 90 days (or thiazolidinediones [TZDs] for at least 24 weeks) prior to screening, and to characterize the relationship between HbA1c reduction and other glycemic parameters in subjects with T2DM.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Placebo

Qualifying Period: Placebo to match ranolazine (1 tablet twice daily) for 14 days.

Treatment Period: Placebo to match ranolazine (Days 1-7: 1 tablet twice daily; 2 tablets twice daily thereafter) for up to 24 weeks.

Participants were required to maintain their diet and exercise regimen.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo to match ranolazine administered orally twice daily.

Diet

Intervention Type: BEHAVIORAL

Participants are instructed to continue the diet regimen prescribed by their physician.

Exercise

Intervention Type: BEHAVIORAL

Participants are instructed to continue the exercise regimen prescribed by their physician.

Ranolazine

Qualifying Period: Placebo to match ranolazine (1 tablet twice daily) for 14 days.

Treatment Period: Ranolazine tablets (Days 1-7: 1 × 500 mg twice daily; 2 × 500 mg twice daily thereafter) for up to 24 weeks.

Participants were required to maintain their diet and exercise regimen.

Group Type: EXPERIMENTAL

Ranolazine

Intervention Type: DRUG

Ranolazine tablets administered orally twice daily.

Placebo

Intervention Type: DRUG

Placebo to match ranolazine administered orally twice daily.

Diet

Intervention Type: BEHAVIORAL

Participants are instructed to continue the diet regimen prescribed by their physician.

Exercise

Intervention Type: BEHAVIORAL

Participants are instructed to continue the exercise regimen prescribed by their physician.

Interventions

Ranolazine

Ranolazine tablets administered orally twice daily.

Intervention Type: DRUG

Placebo

Placebo to match ranolazine administered orally twice daily.

Intervention Type: DRUG

Diet

Participants are instructed to continue the diet regimen prescribed by their physician.

Intervention Type: BEHAVIORAL

Exercise

Participants are instructed to continue the exercise regimen prescribed by their physician.

Intervention Type: BEHAVIORAL

Other Intervention Names

Ranexa®

Eligibility Criteria

Inclusion Criteria

• Written informed consent
• Males and females, 18 to 75 years old, inclusive
• Documented history of T2DM
• Treatment naïve to antihyperglycemic therapy or having received no prior treatment with antihyperglycemic therapy for at least 90 days (TZDs for at least 24 weeks) prior to screening
• Body mass index (BMI) 25 kg/m2 to 45 kg/m2 inclusive at screening
• HbA1c 7% - 10%, inclusive at screening and at the end of the Qualifying Period (Day 14 +2 days)
• Fasting serum glucose (FSG) of ≥ 130 mg/dL (7.2 mmol/L) and ≤ 240 mg/dL (13.3 mmol/L) at screening and at the end of the Qualifying Period (Day 14 +2 days). A one-time central laboratory re-test of FSG is allowed in subjects with an initial central laboratory FSG ≥ 125 mg/dL (6.9 mmol/L) and < 130 mg/dL (7.2 mmol/L) who are otherwise eligible as determined by the investigator.
• Fasting serum C-peptide ≥ 0.8 ng/mL at screening
• Able and willing to comply with all study procedures during the course of the study
• Females of child-bearing potential must have a negative pregnancy test at screening and must agree to use highly effective contraception methods from screening throughout the duration of the Treatment Period and for 14 days following the last dose of study drug
• At least 80% compliant with dosing during the Qualifying Period

Exclusion Criteria

• History of or current diagnosis of type 1 diabetes mellitus
• History of diabetic ketoacidosis, ketosis-prone diabetes, or hyperosmolar hyperglycemic coma
• History of a severe episode of hypoglycemia (≥ 1 episode within 3 months prior to screening or ≥ 2 episodes within 6 months prior to screening), defined as hypoglycemia requiring 3rd party assistance to actively administer carbohydrate, glucagon, or other resuscitative actions due to severe impairment in consciousness or behavior
• Clinically significant complications of diabetes that, in the judgment of the investigator, would make the subject unsuitable to participate in this study
• History of any clinically significant cardiovascular or cerebrovascular event (eg, myocardial infarction [MI], acute coronary syndrome [ACS], recent coronary revascularization [including coronary artery bypass graft procedures or percutaneous coronary intervention], transient ischemic attack or ischemic stroke) ≤ 3 months prior to screening
• Inadequately controlled or unstable hypertension as defined by systolic blood pressure (SBP) > 160 mmHg or diastolic blood pressure (DBP) > 100 mmHg at screening and randomization
• Prolonged QTc interval > 500 msec by ECG at screening, a personal or family history of QTc prolongation, congenital long QT syndrome, or subjects who are receiving drugs that prolong the QTc interval, such as Class Ia or Class III antiarrhythmic agents, erythromycin, and certain antipsychotics (eg, ziprasidone)
• History of bariatric surgery at any time in the past or any other surgery < 2 months before screening, or planning to undergo surgery during the study. Subjects with a planned minor surgery may be enrolled upon approval by the Medical Monitor.
• Any other hospitalization in the 14 days prior to screening or planned hospitalization at any time during the study
• Significant weight change (± 5%) < 2 months prior to screening or on a weight-loss program and is not in the maintenance phase at screening
• Severe renal impairment, defined as an estimated glomerular filtration rate (eGFR) by the Modification of Diet in Renal Disease (MDRD) equation < 30 mL/min/1.73 m2 at screening or undergoing any type of dialysis at screening or planning to undergo any type of dialysis during the course of the study.
• History of liver cirrhosis (Child-Pugh Class A, B or C)
• Active liver disease and/or significant abnormal liver function defined as aspartate aminotransferase (AST) > 3x upper limit of the normal range (ULN) and/or alanine aminotransferase (ALT) > 3x ULN and/or serum total bilirubin > 2.0 mg/dL
• History of cancer (except non-melanomic skin cancers or cervical in situ) within 5 years prior to screening
• History of alcohol or other drug abuse < 12 months prior to screening
• Any other clinically significant existing medical or psychiatric condition, including clinically significant laboratory abnormalities, or one requiring further evaluation that, in the opinion of the investigator, could interfere with conduct of the study or interpretation of the data
• Prior treatment with open-label ranolazine or known hypersensitivity or intolerance to ranolazine or any of its excipients
• Treatment with strong or moderate cytochrome (CYP)3A inhibitors or P-glycoprotein (P-gp) inhibitors within 14 days prior to randomization
• Treatment with CYP3A inducers or P-gp inducers within 14 days prior to randomization
• Treatment with CYP3A4 substrates with a narrow therapeutic range (eg, cyclosporine, tacrolimus, sirolimus) within 14 days prior to randomization
• Treatment with simvastatin at a daily dose > 20 mg or lovastatin at a daily dose > 40 mg, within 14 days prior to randomization
• Weight-loss medication or anti-obesity medication (prescription or nonprescription) < 3 months prior to screening
• Treatment with niacin > 200 mg daily; if receiving ≤ 200 mg daily, should be on stable doses for ≥ 90 days prior to screening and for the duration of the study
• Expected or current treatment with systemic corticosteroids (oral or injectable) for > 14 days from screening through the end of the Treatment Period. Topical or inhaled corticosteroid formulations are permitted at any time during the study
• If receiving thyroid replacement therapy, should be on stable doses for at least 6 weeks prior to randomization
• Hemoglobin < 12 g/dL for males; or < 11 g/dL for females, at screening
• Participation in another clinical study involving an investigational drug or device < 30 days prior to screening; participation in another clinical study involving an antihyperglycemic therapy < 90 days prior to screening
• Donation of blood < 2 months prior to screening; plans to donate blood while participating in the study
• Females who are pregnant or breastfeeding
• Other condition(s) that, in the opinion of the investigator, would compromise the safety of the subject, would prevent compliance with the study protocol (including the ability to comply with Mixed Meal Tolerance Test [MMTT]), or would compromise the quality of the clinical study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Thunderbird Internal Medicine/Clinical Research Advantage

Glendale, Arizona, United States

Central Phoenix Medical Clinic

Phoenix, Arizona, United States

Desert Sun Clinical Research, LLC

Tucson, Arizona, United States

Eclipse Clinical Research

Tucson, Arizona, United States

North Central Arkansas Medical Associates

Mountain Home, Arkansas, United States

Paul W. Davis, MD, Private Practice

Pine Bluff, Arkansas, United States

Southland Clinical Research Center, Inc.

Fountain Valley, California, United States

Global Research Management

Glendale, California, United States

National Research Institute

Los Angeles, California, United States

Spectrum Clinical Research Institute, Inc

Moreno Valley, California, United States

Sacramento Heart and Vascular Medical Associates

Sacramento, California, United States

Clearview Medical Research LLC

Santa Clarita, California, United States

Infosphere Clinical Research

West Hills, California, United States

Boca Raton Clinical Research Associates, Inc

Boca Raton, Florida, United States

PAB Clinical Research

Brandon, Florida, United States

Florida Research Network, LLC

Gainesville, Florida, United States

A G A Clinical Trials

Hialeah, Florida, United States

Jacksonville Center for Clinical Research

Jacksonville, Florida, United States

Baptist Diabetes Associates

Miami, Florida, United States

NextPhase Clinical Trials, Inc.

Miami Beach, Florida, United States

Precision Research Organization

Miami Lakes, Florida, United States

Suncoast Clinical Research

New Port Richey, Florida, United States

Florida Institute for Clinical Research LLC

Orlando, Florida, United States

Regenerate Clinical Trials

South Miami, Florida, United States

Synergy Therapeutic Partners

Atlanta, Georgia, United States

CTL Research

Eagle, Idaho, United States

Cedar-Crosse Research Center

Chicago, Illinois, United States

LaPorte County Institute for Clinical Research

Michigan City, Indiana, United States

Clinical Trials Management, LLC

Metairie, Louisiana, United States

MD Medical Research

Oxon Hill, Maryland, United States

IRC Clinics, Inc

Towson, Maryland, United States

Associated Internal Medicine Specialists, P.C.

Battle Creek, Michigan, United States

Albuquerque Clinical Trials

Albuquerque, New Mexico, United States

University of New Mexico Clinical and Translational Science Center

Albuquerque, New Mexico, United States

Clinical Research Solution

New York, New York, United States

PMG Research of Charlotte

Charlotte, North Carolina, United States

PharmQuest

Greensboro, North Carolina, United States

PMG Research of Salisbury

Salisbury, North Carolina, United States

Clinical Inquest Center, Ltd.

Beavercreek, Ohio, United States

Infinity Research Group, LLC

Oklahoma City, Oklahoma, United States

Blair Medical Associates, Inc, Station Medical Center

Altoona, Pennsylvania, United States

Southeastern Research Associates, Inc.

Taylors, South Carolina, United States

HCCA Clinical Research Solutions

Columbia, Tennessee, United States

HCCA Clinical Research Solution

Jackson, Tennessee, United States

New Phase Research & Development

Knoxville, Tennessee, United States

HCCA Clinical Research Solutions

Smyrrna, Tennessee, United States

The University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, United States

Excel Clinical Research, LLC

Houston, Texas, United States

Texas Center for Drug Development, PA

Houston, Texas, United States

Humble Cardiology Associates

Humble, Texas, United States

Juno Research, LLC

Katy, Texas, United States

Cetero Research

San Antonio, Texas, United States

Discovery Clinical Trials

San Antonio, Texas, United States

Highland Clinical Research

Salt Lake City, Utah, United States

Jean Brown Research

Salt Lake City, Utah, United States

Burke Internal Medicine & Research

Burke, Virginia, United States

Manassas Clinical Research Center

Manassas, Virginia, United States

Nemocnice s poliklinikou Havirov

Havířov, Moravskoslezský kraj, Czechia

Drug Research Center

Balatonfüred, , Hungary

Synexus Hungary Ltd

Budapest, , Hungary

Markhot Ferenc Hospital

Eger, , Hungary

Kanizsai Dorottya Hospital

Nagykanizsa, , Hungary

Borbanya Praxis Kft., Outpatient Clinic

Nyíregyháza, , Hungary

Medifarma 98

Nyíregyháza, , Hungary

Zala County Hospital

Zalaegerszeg, , Hungary

LANDA - Specjalistyczne Gabinety Lekarskie

Krakow, Lesser Poland Voivodeship, Poland

NZOZ Centrum Badan Klinicznych Oswiecim

Oswięcim, Lesser Poland Voivodeship, Poland

NZOZ Regionalna Poradnia Diabetologiczna

Wroclaw, Lower Silesian Voivodeship, Poland

NZOZ Centrum Badan Klinicznych

Wroclaw, Lower Silesian Voivodeship, Poland

NZOZ Centrum Osteporozy i Chorob Kostno-Stawowych J.Badurski Sp.j.

Bialystok, , Poland

Leszek Romanowski Barbara Romanowska "DIABET" Centrum Medyczne s.c.

Chrzanów, , Poland

NZOZ Specjalistyczna Przychodnia Medyczna Atopia

Krakow, , Poland

NZOZ Cereo-Med Sp. z o.o.

Lodz, , Poland

Specjalistyzny Ośrodek Lecznicz-Badawczy

Ostróda, , Poland

Miedzyleski Szpital Specjalistyczny w Warszawie

Warsaw, , Poland

SPZOZ Uniwersytecki Szpital Kliniczny Nr 1 im. Norberta Barlickiego Uniwersytetu Medycznego w Łodzi, Oddział Kliniczny Diabetologii

Lodz, Łódź Voivodeship, Poland

NZOZ Centrum Medyczne Szpital Sw. Rodziny

Lodz, Łódź Voivodeship, Poland

NZOZ Polimedica

Zgierz, Łódź Voivodeship, Poland

NZOZ PrimaMED

Kielce, Świętokrzyskie Voivodeship, Poland

CMI Morosanu V. Magdalena

Galati, Galați County, Romania

Spitalul Clinic Judetean de Urgenta "Sf. Apostol Andrei" Galati

Galati, Galați County, Romania

Spital Clinic Judetean de Urgenta Oradea Stationarul 1

Oradea, Jud Bihor, Romania

Vitadiab SRL - Cabinet Medical Dr. Barabas Alina SRL

Brasov, Jud Brasov, Romania

Consultmed SRL

Iași, Jud. Iasi, Romania

CMI Diabet Nutritie Boli Metabolice Dr. Pop Lavinia

Baia Mare, Jud. Maramures, Romania

Diabmed Dr. Popescu Alexandrina SRL

Ploieşti, Prahova, Romania

Institutul de Diabet, Nutritie si Boli Metabolice "Dr. N. C. Paulescu"

Bucharest, , Romania

Tehnomed Trading Srl

Bucharest, , Romania

O.D. Medica Srl

Bucharest, , Romania

Centru Medical Dr. Negrisanu

Timisoara, Jud. Timis, , Romania

3rd Central Military Clinical Hospital named after A.A.Vishnevskogo

Arkhangel'skoye, , Russia

GOU VPO "Chita State Medical Academy" of Minzdravsocrazvitie RF

Chita, , Russia

"Clinic of New Medical Technology" Company Limited

Dzerzhinskiy, , Russia

Kemerovo Regional Clinical Hospital

Kemerovo, , Russia

"Krasnoyarsk State Medical University n.a. Prof. V.F. Voyno-Yasenetsky

Krasnoyarsk, , Russia

State Healthcare Institution of Moscow "Cardiologival Dispensary #2 of Management Department of South Administrative District"

Moscow, , Russia

Central Clinical Hospital of Russian Academy of Sciences

Moscow, , Russia

Medical Sanitary Unit of Minestry of Internal Affairs of Russia in Moscow

Moscow, , Russia

Moscow City Clinical Hospital #63

Moscow, , Russia

City Clinical Hospital # 13 of Avtozavodsky District of Nizhniy Novgorod

Nizhny Novgorod, , Russia

Novosibirsk State Medical University

Novosibirsk, , Russia

LLC "Reafan"

Novosibirsk, , Russia

Scientific Research Institute of Physiology of Siberian Department RAMS

Novosibirsk, , Russia

City Hospital # 38 named after N A Semashko

Pushkin, , Russia

Rostov State Medical University

Rostov-on-Don, , Russia

Ryazan State Medical University

Ryazan, , Russia

Saint-Petersburg City Outpatient Clinic#37

Saint Petersburg, , Russia

Medinet, LLC

Saint Petersburg, , Russia

North-Western State Medical Unversity n.a. I.I.Mechnikov

Saint Petersburg, , Russia

Military Medical Academy named after S.M. Kirov

Saint Petersburg, , Russia

Saint-Petersburg state budgetary healthcare institution "City Polyclinic #109"

Saint Petersburg, , Russia

Alexanders City Hospital

Saint Petersburg, , Russia

Clinical Hospital #122 n.a. Sokolov of FMBA

Saint Petersburg, , Russia

ANO "Medical Centre "XXI century"

Saint Petersburg, , Russia

St. Elizabeth City Hospital

Saint Petersburg, , Russia

Krestovsky Island Medical Institute, LLC

Saint Petersburg, , Russia

Federal Centre of Heart, Blood and Endocrinology named after V.A. Almazov

Saint Petersburg, , Russia

Military Medical Academy named after S.M. Kirov

Saint Petersburg, , Russia

International Medical Center "SOGAZ", LLC

Saint Petersburg, , Russia

Saint-Petersburg City Pokrovskaya Hospital

Saint Petersburg, , Russia

Center "Diabetes", LLC

Samara, , Russia

Smolensk State Medical Academy, Sanatorium-Preventorium

Smolensk, , Russia

Tyumen State Medical Academy

Tyumen, , Russia

Voronezh Regional Clinical Hospital #1

Voronezh, , Russia

City Hospital named after N.A.Semashko

Yaroslavl, , Russia

Clinical Hospital for Emergency Care named after N.V. Solovyov

Yaroslavl, , Russia

Medical Sanitary Unit of Novo-Yaroslavsky Oil Refinery

Yaroslavl, , Russia

Yaroslavl Regional Clinical Hospital

Yaroslavl, , Russia

The Urals State Medical Academy

Yekaterinburg, , Russia

Clinical Center of Serbia

Belgrade, , Serbia

Clinical Center of Kragujevac

Kragujevac, , Serbia

METABOLKLINIK s.r.o.

Bratislava, Bratislava Region, Slovakia

Metabolic Center of Dr. Katarina Raslova Ltd.

Bratislava, Bratislava Region, Slovakia

"Diabetologicka a metabolicka ambulancia Human-care s.r.o"

Košice, Košice Region, Slovakia

ARETEUS s.r.o., Diabetologicka ambulancia

Trebišov, Košice Region, Slovakia

MediVet s.r.o.

Malacky, , Slovakia

ENDIAMED s.r.o

Dolný Kubín, Žilina Region, Slovakia

MEDIVASA s.r.o.

Žilina, Žilina Region, Slovakia

Newkwa Medical Centre

Newlands West, Durban, South Africa

Global Clinical Trials

Pretoria, Pretoria, South Africa

Netcare Umhlanga Medical Centre

Kwa Zulu Natal, Umhlanga, Durban, South Africa

Worthwhile Clinical Trials

Benoni, , South Africa

Centre for Diabetes, Asthma and Allergy

Johannesburg, , South Africa

Soweto Clinical Trial Centre

Johannesburg, , South Africa

Aliwal Shoal Medical & Clinical Trial Centre

Kwa Zulu Natal, , South Africa

Helderberg Clinical Trials Centre

Somerset West, , South Africa

Tiervlei Trial Centre

Western Cape, , South Africa

City Clinical Hospital#9, Dnipropetrovsk State Medical Academy

Dnipropetrovsk, , Ukraine

Educational Scientific Medical Centre "University clinic" of Donetsk National Medical University n.a. M.Gorkiy

Donetsk, , Ukraine

State Institution "Institute of Problems of Endocrine Pathology n.a. V.Y. Danylevsky of NAMS of Ukraine"

Kharkiv, , Ukraine

Administration of Medical Service and Rehabilitation of "ARTEM" State Holding Company

Kyiv, , Ukraine

National Medical University n.a. O.O. Bogomolets, Chair of Family Medicine based on Outpatient Clinic # 2 of Shevchenkovsky District

Kyiv, , Ukraine

V. P. Komissarenko Institute of Endocrinology and Metabolism of AMS of Ukraine

Kyiv, , Ukraine

Municipal Institution Lutsk City Clinical Hospital

Lutsk, , Ukraine

Lviv Regional Endocrinology Dispensary

Lviv, , Ukraine

Odessa State Medical University

Odesa, , Ukraine

Public Institution "City Outpatients' Hospital #20"

Odesa, , Ukraine

Vinnytsya Regional Clinical Endocrinology Dispensary

Vinnytsia, , Ukraine

Zhytomyr Regional Clinical Hospital

Zhytomyr, , Ukraine

Countries

United States; Czechia; Hungary; Poland; Romania; Russia; Serbia; Slovakia; South Africa; Ukraine

References

Eckel RH, Henry RR, Yue P, Dhalla A, Wong P, Jochelson P, Belardinelli L, Skyler JS. Effect of Ranolazine Monotherapy on Glycemic Control in Subjects With Type 2 Diabetes. Diabetes Care. 2015 Jul;38(7):1189-96. doi: 10.2337/dc14-2629. Epub 2015 Jun 6.

Reference Type: DERIVED

PMID: 26049552 (View on PubMed)

Other Identifiers

GS-US-259-0131

Identifier Type: -

Identifier Source: org_study_id