Ranolazine Monotherapy in Subjects With Type 2 Diabetes Mellitus

NCT01472185 | Completed Phase 3 Results DMC

• 1 other identifier: GS-US-259-0131
• Study Type: interventional
• Target: 465
• Locations: 10 countries
• Sites: 159

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

Keywords

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24

  The average (mean) change from baseline in HbA1c at Week 24 was analyzed.

  Baseline; Week 24

Secondary Outcomes (4)

• Change From Baseline in Fasting Serum Glucose at Week 24

  Baseline; Week 24

• Percentage of Participants With HbA1c < 7% at Week 24

  Week 24

• Change From Baseline in 2-hour Postprandial Serum Glucose at Week 24

  Baseline; Week 24

• Change From Baseline in Incremental Change of 2-hour Postprandial Serum Glucose at Week 24

  Baseline; Week 24

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo; Behavioral: Diet; Behavioral: Exercise

Ranolazine

EXPERIMENTAL

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.

Drug: Ranolazine; Drug: Placebo; Behavioral: Diet; Behavioral: Exercise

Interventions

Ranolazine DRUG

Ranolazine tablets administered orally twice daily.

Also known as: Ranexa®

Ranolazine

Placebo DRUG

Placebo to match ranolazine administered orally twice daily.

Placebo; Ranolazine

Diet BEHAVIORAL

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

Placebo; Ranolazine

Exercise BEHAVIORAL

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

Placebo; Ranolazine

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (159)

Thunderbird Internal Medicine/Clinical Research Advantage

Glendale, Arizona, 85306, United States

Location

Central Phoenix Medical Clinic

Phoenix, Arizona, 85020, United States

Location

Desert Sun Clinical Research, LLC

Tucson, Arizona, 85710, United States

Location

Eclipse Clinical Research

Tucson, Arizona, 85745, United States

Location

North Central Arkansas Medical Associates

Mountain Home, Arkansas, 72653, United States

Location

Paul W. Davis, MD, Private Practice

Pine Bluff, Arkansas, 71603, United States

Location

Southland Clinical Research Center, Inc.

Fountain Valley, California, 92708, United States

Location

Global Research Management

Glendale, California, 91205, United States

Location

National Research Institute

Los Angeles, California, 90057, United States

Location

Spectrum Clinical Research Institute, Inc

Moreno Valley, California, 92553, United States

Location

Sacramento Heart and Vascular Medical Associates

Sacramento, California, 95825, United States

Location

Clearview Medical Research LLC

Santa Clarita, California, 91350, United States

Location

Infosphere Clinical Research

West Hills, California, 91307, United States

Location

Boca Raton Clinical Research Associates, Inc

Boca Raton, Florida, 33432, United States

Location

PAB Clinical Research

Brandon, Florida, 33511, United States

Location

Florida Research Network, LLC

Gainesville, Florida, 32605-4253, United States

Location

A G A Clinical Trials

Hialeah, Florida, 33012, United States

Location

Jacksonville Center for Clinical Research

Jacksonville, Florida, 32216, United States

Location

Baptist Diabetes Associates

Miami, Florida, 33156, United States

Location

NextPhase Clinical Trials, Inc.

Miami Beach, Florida, 33140, United States

Location

Precision Research Organization

Miami Lakes, Florida, 33016, United States

Location

Suncoast Clinical Research

New Port Richey, Florida, 34652, United States

Location

Florida Institute for Clinical Research LLC

Orlando, Florida, 32822, United States

Location

Regenerate Clinical Trials

South Miami, Florida, 33143, United States

Location

Synergy Therapeutic Partners

Atlanta, Georgia, 30127, United States

Location

CTL Research

Eagle, Idaho, 83616, United States

Location

Cedar-Crosse Research Center

Chicago, Illinois, 60607, United States

Location

LaPorte County Institute for Clinical Research

Michigan City, Indiana, 46360, United States

Location

Clinical Trials Management, LLC

Metairie, Louisiana, 70006, United States

Location

MD Medical Research

Oxon Hill, Maryland, 20745, United States

Location

IRC Clinics, Inc

Towson, Maryland, 21204, United States

Location

Associated Internal Medicine Specialists, P.C.

Battle Creek, Michigan, 49015, United States

Location

Albuquerque Clinical Trials

Albuquerque, New Mexico, 87102, United States

Location

University of New Mexico Clinical and Translational Science Center

Albuquerque, New Mexico, 87131, United States

Location

Clinical Research Solution

New York, New York, 10016, United States

Location

PMG Research of Charlotte

Charlotte, North Carolina, 28202, United States

Location

PharmQuest

Greensboro, North Carolina, 27408, United States

Location

PMG Research of Salisbury

Salisbury, North Carolina, 28144, United States

Location

Clinical Inquest Center, Ltd.

Beavercreek, Ohio, 45431, United States

Location

Infinity Research Group, LLC

Oklahoma City, Oklahoma, 73103, United States

Location

Blair Medical Associates, Inc, Station Medical Center

Altoona, Pennsylvania, 16602, United States

Location

Southeastern Research Associates, Inc.

Taylors, South Carolina, 29687, United States

Location

HCCA Clinical Research Solutions

Columbia, Tennessee, 38401, United States

Location

HCCA Clinical Research Solution

Jackson, Tennessee, 38305, United States

Location

New Phase Research & Development

Knoxville, Tennessee, 37923, United States

Location

HCCA Clinical Research Solutions

Smyrrna, Tennessee, 37167, United States

Location

The University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, 75390, United States

Location

Excel Clinical Research, LLC

Houston, Texas, 77081, United States

Location

Texas Center for Drug Development, PA

Houston, Texas, 77081, United States

Location

Humble Cardiology Associates

Humble, Texas, 77338, United States

Location

Juno Research, LLC

Katy, Texas, 77450, United States

Location

Cetero Research

San Antonio, Texas, 78237, United States

Location

Discovery Clinical Trials

San Antonio, Texas, 78258, United States

Location

Highland Clinical Research

Salt Lake City, Utah, 84124, United States

Location

Jean Brown Research

Salt Lake City, Utah, 84124, United States

Location

Burke Internal Medicine & Research

Burke, Virginia, 22015, United States

Location

Manassas Clinical Research Center

Manassas, Virginia, 20110, United States

Location

Nemocnice s poliklinikou Havirov

Havířov, Moravskoslezský kraj, 736 01, Czechia

Location

Drug Research Center

Balatonfüred, 8230, Hungary

Location

Synexus Hungary Ltd

Budapest, 1036, Hungary

Location

Markhot Ferenc Hospital

Eger, 3300, Hungary

Location

Kanizsai Dorottya Hospital

Nagykanizsa, 8800, Hungary

Location

Borbanya Praxis Kft., Outpatient Clinic

Nyíregyháza, 4400, Hungary

Location

Medifarma 98

Nyíregyháza, 4400, Hungary

Location

Zala County Hospital

Zalaegerszeg, 08900, Hungary

Location

LANDA - Specjalistyczne Gabinety Lekarskie

Krakow, Lesser Poland Voivodeship, 30-015, Poland

Location

NZOZ Centrum Badan Klinicznych Oswiecim

Oswięcim, Lesser Poland Voivodeship, 32-600, Poland

Location

NZOZ Regionalna Poradnia Diabetologiczna

Wroclaw, Lower Silesian Voivodeship, 50-127, Poland

Location

NZOZ Centrum Badan Klinicznych

Wroclaw, Lower Silesian Voivodeship, 50-349, Poland

Location

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

Bialystok, 15-461, Poland

Location

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

Chrzanów, 32-500, Poland

Location

NZOZ Specjalistyczna Przychodnia Medyczna Atopia

Krakow, 31-159, Poland

Location

NZOZ Cereo-Med Sp. z o.o.

Lodz, 92-003, Poland

Location

Specjalistyzny Ośrodek Lecznicz-Badawczy

Ostróda, 14-100, Poland

Location

Miedzyleski Szpital Specjalistyczny w Warszawie

Warsaw, 04-749, Poland

Location

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

Lodz, Łódź Voivodeship, 90-153, Poland

Location

NZOZ Centrum Medyczne Szpital Sw. Rodziny

Lodz, Łódź Voivodeship, 90-302, Poland

Location

NZOZ Polimedica

Zgierz, Łódź Voivodeship, 95-100, Poland

Location

NZOZ PrimaMED

Kielce, Świętokrzyskie Voivodeship, 25-364, Poland

Location

CMI Morosanu V. Magdalena

Galati, Galați County, 800371, Romania

Location

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

Galati, Galați County, 800578, Romania

Location

Spital Clinic Judetean de Urgenta Oradea Stationarul 1

Oradea, Jud Bihor, 410169, Romania

Location

Vitadiab SRL - Cabinet Medical Dr. Barabas Alina SRL

Brasov, Jud Brasov, 500269, Romania

Location

Consultmed SRL

Iași, Jud. Iasi, 700547, Romania

Location

CMI Diabet Nutritie Boli Metabolice Dr. Pop Lavinia

Baia Mare, Jud. Maramures, 430123, Romania

Location

Diabmed Dr. Popescu Alexandrina SRL

Ploieşti, Prahova, 100163, Romania

Location

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

Bucharest, 020042, Romania

Location

Tehnomed Trading Srl

Bucharest, 020354, Romania

Location

O.D. Medica Srl

Bucharest, 020725, Romania

Location

Centru Medical Dr. Negrisanu

Timisoara, Jud. Timis, 300456, Romania

Location

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

Arkhangel'skoye, 143420, Russia

Location

GOU VPO "Chita State Medical Academy" of Minzdravsocrazvitie RF

Chita, 672090, Russia

Location

"Clinic of New Medical Technology" Company Limited

Dzerzhinskiy, 140091, Russia

Location

Kemerovo Regional Clinical Hospital

Kemerovo, 650066, Russia

Location

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

Krasnoyarsk, 660062, Russia

Location

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

Moscow, 117556, Russia

Location

Central Clinical Hospital of Russian Academy of Sciences

Moscow, 117593, Russia

Location

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

Moscow, 127299, Russia

Location

Moscow City Clinical Hospital #63

Moscow, 129090, Russia

Location

City Clinical Hospital # 13 of Avtozavodsky District of Nizhniy Novgorod

Nizhny Novgorod, 603018, Russia

Location

Novosibirsk State Medical University

Novosibirsk, 630087, Russia

Location

LLC "Reafan"

Novosibirsk, 630099, Russia

Location

Scientific Research Institute of Physiology of Siberian Department RAMS

Novosibirsk, 630117, Russia

Location

City Hospital # 38 named after N A Semashko

Pushkin, 196601, Russia

Location

Rostov State Medical University

Rostov-on-Don, 344022, Russia

Location

Ryazan State Medical University

Ryazan, 390005, Russia

Location

Saint-Petersburg City Outpatient Clinic#37

Saint Petersburg, +011 78123152068, Russia

Location

Medinet, LLC

Saint Petersburg, 190000, Russia

Location

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

Saint Petersburg, 191015, Russia

Location

Military Medical Academy named after S.M. Kirov

Saint Petersburg, 191124, Russia

Location

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

Saint Petersburg, 192283, Russia

Location

Alexanders City Hospital

Saint Petersburg, 193312, Russia

Location

Clinical Hospital #122 n.a. Sokolov of FMBA

Saint Petersburg, 194291, Russia

Location

ANO "Medical Centre "XXI century"

Saint Petersburg, 194354, Russia

Location

St. Elizabeth City Hospital

Saint Petersburg, 195257, Russia

Location

Krestovsky Island Medical Institute, LLC

Saint Petersburg, 197042, Russia

Location

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

Saint Petersburg, 197341, Russia

Location

Military Medical Academy named after S.M. Kirov

Saint Petersburg, 198013, Russia

Location

International Medical Center "SOGAZ", LLC

Saint Petersburg, 198168, Russia

Location

Saint-Petersburg City Pokrovskaya Hospital

Saint Petersburg, 199106, Russia

Location

Center "Diabetes", LLC

Samara, 443067, Russia

Location

Smolensk State Medical Academy, Sanatorium-Preventorium

Smolensk, 214019, Russia

Location

Tyumen State Medical Academy

Tyumen, 625023, Russia

Location

Voronezh Regional Clinical Hospital #1

Voronezh, 394082, Russia

Location

City Hospital named after N.A.Semashko

Yaroslavl, 150002, Russia

Location

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

Yaroslavl, 150003, Russia

Location

Medical Sanitary Unit of Novo-Yaroslavsky Oil Refinery

Yaroslavl, 150023, Russia

Location

Yaroslavl Regional Clinical Hospital

Yaroslavl, 150062, Russia

Location

The Urals State Medical Academy

Yekaterinburg, 620102, Russia

Location

Clinical Center of Serbia

Belgrade, 11000, Serbia

Location

Clinical Center of Kragujevac

Kragujevac, 34000, Serbia

Location

METABOLKLINIK s.r.o.

Bratislava, Bratislava Region, 811 01, Slovakia

Location

Metabolic Center of Dr. Katarina Raslova Ltd.

Bratislava, Bratislava Region, 831 01, Slovakia

Location

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

Košice, Košice Region, 04001, Slovakia

Location

ARETEUS s.r.o., Diabetologicka ambulancia

Trebišov, Košice Region, 07501, Slovakia

Location

MediVet s.r.o.

Malacky, 901 01, Slovakia

Location

ENDIAMED s.r.o

Dolný Kubín, Žilina Region, 02601, Slovakia

Location

MEDIVASA s.r.o.

Žilina, Žilina Region, 010 10, Slovakia

Location

Newkwa Medical Centre

Newlands West, Durban, 4037, South Africa

Location

Global Clinical Trials

Pretoria, Pretoria, 0001, South Africa

Location

Netcare Umhlanga Medical Centre

Kwa Zulu Natal, Umhlanga, Durban, 4320, South Africa

Location

Worthwhile Clinical Trials

Benoni, 1500, South Africa

Location

Centre for Diabetes, Asthma and Allergy

Johannesburg, 01829, South Africa

Location

Soweto Clinical Trial Centre

Johannesburg, 1818, South Africa

Location

Aliwal Shoal Medical & Clinical Trial Centre

Kwa Zulu Natal, 4170, South Africa

Location

Helderberg Clinical Trials Centre

Somerset West, 7130, South Africa

Location

Tiervlei Trial Centre

Western Cape, 7530, South Africa

Location

City Clinical Hospital#9, Dnipropetrovsk State Medical Academy

Dnipropetrovsk, 49023, Ukraine

Location

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

Donetsk, 83003, Ukraine

Location

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

Kharkiv, 61002, Ukraine

Location

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

Kyiv, 04050, Ukraine

Location

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

Kyiv, 04050, Ukraine

Location

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

Kyiv, 04114, Ukraine

Location

Municipal Institution Lutsk City Clinical Hospital

Lutsk, 43024, Ukraine

Location

Lviv Regional Endocrinology Dispensary

Lviv, 79010, Ukraine

Location

Odessa State Medical University

Odesa, 65039, Ukraine

Location

Public Institution "City Outpatients' Hospital #20"

Odesa, 65114, Ukraine

Location

Vinnytsya Regional Clinical Endocrinology Dispensary

Vinnytsia, 21010, Ukraine

Location

Zhytomyr Regional Clinical Hospital

Zhytomyr, 10002, Ukraine

Location

Related Publications (1)

• 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.

  PMID: 26049552 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Ranolazine; Diet; Exercise

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Results Point of Contact

• Title: Clinical Trial Disclosures
• Organization: Gilead Sciences, Inc.

ClinicalTrialDisclosures@gilead.com

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2011
• First Posted: November 16, 2011
• Study Start: November 1, 2011
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: October 24, 2014
• Results First Posted: October 15, 2014

Record last verified: 2014-10

Locations

SE (2); ZA (9); SL (7); US (57); CZ (1); PL (14); HU (7); RO (11); UA (12); RU (39)