A Phase 3 Study of Ranolazine in Subjects With Type 2 Diabetes Who Are Inadequately Controlled on Metformin Alone

September 17, 2014 updated by: Gilead Sciences

A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Ranolazine When Added to Metformin in Subjects With Type 2 Diabetes Mellitus

This is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study to determine the effect of ranolazine when added to metformin on glycemic control in adults with type 2 diabetes mellitus (T2DM) who are inadequately controlled despite current treatment with stable metformin therapy in addition to diet and exercise.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

442

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • British Columbia
      • Kelowna, British Columbia, Canada, V1Y 3G8
        • The Medical Arts Health Research Group
      • Vancouver, British Columbia, Canada, V5Z 1L8
        • Diabetes Research Clinic
    • Ontario
      • Cambridge, Ontario, Canada, N1R7L6
        • Joanne F. Liutkus Medicine Professional Corporation
      • Hawkesbury, Ontario, Canada, K6A 1A1
        • Source Unique Research
  • Czech Republic
    • Moravskoslezsky kraj
      • Havirov, Moravskoslezsky kraj, Czech Republic, 736-01
        • Nemocnice s poliklinikou Havirov
    • Praha
      • Praha 8, Praha, Czech Republic, 18100
        • ResTrial s.r.o.
  • Hungary
      • Budapest, Hungary, 1036
        • Synexus Hungary Ltd
      • Komárom, Hungary, 2900
        • Selye János Kórház és Rendel?intézet, Belgyógyászati Szakrendelés
      • Nagykanizsa, Hungary, 8800
        • Kanizsai Dorottya Hospital
      • Nyíregyháza, Hungary, 4400
        • Medifarma 98
      • Nyíregyháza, Hungary, 4405
        • Borbanya Praxis Kft., Outpatient Clinic
  • India
    • Andhra Pradesh
      • Hyderabad, Andhra Pradesh, India, 500034
        • Diabetomics India
    • Gujarat
      • Ahmadabad, Gujarat, India, 380015
        • DHL Research Centre, 2nd Floor
      • Ahmadabad, Gujarat, India, 380015
        • Dia Care- A Complete Diabetes Care Center
      • Vadodara, Gujarat, India, 390001
        • Baroda Medical College and SSG Hospital
      • Vadodara, Gujarat, India, 390015
        • Banker's Heart Institute
    • Karnataka
      • Bangalore, Karnataka, India, 560017
        • Manipal Hospital
      • Bangalore, Karnataka, India, 560003
        • Endocrinology & Diabetes Research Centre
      • Bangalore, Karnataka, India, 560038
        • Endocrinology Diabetes Centre
      • Bangalore, Karnataka, India, 560043
        • Bangalore Diabetes Hospital
      • Bangalore, Karnataka, India, 560052
        • The Bangalore Diabetes Hospital
      • Bangalore, Karnataka, India, 560078
        • Jnana Sanjeevani Medical Center
      • Mangalore, Karnataka, India, 575003
        • Vinaya Hospital and Research Centre
    • Maharashtra
      • Mumbai, Maharashtra, India, 400012
        • Seth G. S. Medical College and KEM Hospital
      • Nagpur, Maharashtra, India, 440012
        • Getwell Hospital and Research Institute
      • Nagpur, Maharashtra, India, 440010
        • Institue of Clinical Endocrinology (I.C.E) and Diabetes Care Unit (D.C.U),
      • Pune, Maharashtra, India, 411011
        • KEM Hospital Research Center
      • Pune, Maharashtra, India, 411011
        • Diabetes Care and Research Centre
    • Punjab
      • Chandigarh, Punjab, India, 160017
        • Fortis City Centre
      • Ludhiana, Punjab, India, 141008
        • Diabetes and Heart Centre
    • Tamilnadu
      • Chennai, Tamilnadu, India, 600028
        • Swamy Diabetes Centre
      • Chennai, Tamilnadu, India, 600086
        • Madras Diabetes Research Foundation
      • Coimbatore, Tamilnadu, India, 641009
        • Kovai Diabetes Speciality Centre & Hospital
  • Israel
      • Beer Sheva, Israel, 84101
        • Soroka University Medical Center
      • Holon, Israel, 58100
        • Edith Wolfson Medical Center
      • Safed, Israel, 13100
        • Ziv Medical Center Safed-Israel
  • Mexico
    • Jalisco
      • Guadalajara, Jalisco, Mexico, 44600
        • Instituto Jalisciense de Investigacion en Diabetes y Obesidad
  • Poland
      • Bialystok, Poland, 15-435
        • Niepubliczy Zaklad Opieki Zdrowotnej (NZOZ) Specjalistyczny Osrodek Internistyczno - Diabetologiczny
      • Gniewkowo, Poland, 88-140
        • NZOZ "Esculap" S.C.
    • Lodzkie
      • Lodz, Lodzkie, Poland, 90242
        • Centrum Terapii Wspolczesnej J.M. Jasnorzewska Sp. Komandytowo - Akcyjna
    • Malopolskie
      • Krakow, Malopolskie, Poland, 30-015
        • LANDA - Specjalistyczne Gabinety Lekarskie
  • Russian Federation
      • Chita, Russian Federation, 672090
        • GOU VPO "Chita State Medical Academy" of Minzdravsocrazvitie RF
      • Dzerzhinskiy, Russian Federation, 140091
        • Clinic of New Medical Technology Company Limited
      • Kemerovo, Russian Federation, 650066
        • Kemerovo Regional Clinical Hospital
      • Moscow, Russian Federation, 119034
        • State Institution of Public Health of Moscow City Endocrinology Dispensary
      • Novosibirsk, Russian Federation, 630087
        • Novosibirsk State Medical University
      • Novosibirsk, Russian Federation, 630099
        • Reafan, LLC
      • Rostov-on-Don, Russian Federation, 344022
        • Rostov State Medical University
      • Ryazan, Russian Federation, 29005
        • Ryazan State Medical University
      • Samara, Russian Federation, 443067
        • Center "Diabetes", LLC
      • Smolensk, Russian Federation, 214019
        • Smolensk State Medical Academy, Sanatorium-Preventorium
      • St. Petersburg, Russian Federation, 190000
        • Medinet, LLC
      • St. Petersburg, Russian Federation, 191015
        • North-Western State Medical Unversity n.a. I.I.Mechnikov
      • St. Petersburg, Russian Federation, 191119
        • Saint-Petersburg City Outpatient Clinic#37
      • St. Petersburg, Russian Federation, 191124
        • Military Medical Academy named after S.M. Kirov
      • St. Petersburg, Russian Federation, 193312
        • Alexanders City Hospital
      • St. Petersburg, Russian Federation, 194291
        • Clinical Hospital #122 n.a. Sokolov of FMBA
      • St. Petersburg, Russian Federation, 197042
        • Krestovsky Island Medical Institute, LLC
      • St. Petersburg, Russian Federation, 197341
        • Federal Centre of Heart, Blood and Endocrinology named after V.A. Almazov
      • St. Petersburg, Russian Federation, 192012
        • City Diabetology Center #4, "City Polyclinic #77"
      • St. Petersburg, Russian Federation, 194354
        • ANO Medical Centre XXI Century
      • St. Petersburg, Russian Federation, 196601
        • City Hospital #38 named after N. A. Semashko
      • St. Petersburg, Russian Federation, 198013
        • Federal State Budget Military Educational Institution Medical Military Academy n. a. S. M. Kirov
      • St. Petersburg, Russian Federation, 198255
        • SPb GBUZ Diagnostic Center #85
      • Yaroslavl, Russian Federation, 150062
        • Yaroslavl Regional Clinical Hospital
      • Yaroslavl, Russian Federation, 150002
        • City Hospital named after N.A.Semashko
  • South Africa
      • Benoni, South Africa, 1500
        • East Rand Research Trading as Worthwhile Clinical Trials
      • Johannesburg, South Africa, 2193
        • Charlotte Maxeke Johannesburg Academic Hospital
      • Kwa Zulu Natal, South Africa, 4170
        • Aliwal Shoal Medical & Clinical Trial Centre
      • Kwa Zulu Natal, South Africa, 4320
        • Netcare Umhlanga Medical Centre
      • Somerset West, South Africa, 7129
        • Helderberg Clinical Trials Centre
    • Durban
      • Congella, Durban, South Africa, 4091
        • Centre for Diabetes and Endocrinology Suite 1
      • Kwa Zulu Natal, Durban, South Africa, 4091
        • Vawda Z Private Practice
      • Newlands West, Durban, South Africa, 4037
        • Newkwa Medical Centre
      • Overport, Durban, South Africa, 4001
        • Drs. Naiker and Naicker Inc.
    • Pretoria
      • Meyerspark, Pretoria, South Africa, 0102
        • Synexus Clinical Research SA (Pty) Ltd
  • Ukraine
      • Donetsk, Ukraine, 83003
        • Educational Scientific Medical Centre, Donetsk National Medical University
      • Kharkiv, Ukraine, 61002
        • State Institution "Institute of Problems of Endocrine Pathology n.a. V.Y. Danylevsky of NAMS of Ukra
      • Kyiv, Ukraine, 04050
        • Administration of Medical Service and Rehabilitation of "ARTEM" State Holding Company
      • Kyiv, Ukraine, 04114
        • V. P. Komissarenko Institute of Endocrinology and Metabolism of AMS of Ukraine
      • Kyiv, Ukraine, 02175
        • Ukrainian Scientific-and-Practical Center of Endocrine Surgery, Transplantation of Endocrine Organs
      • Kyiv, Ukraine, 03049
        • Department of Endocrinology of Railway Clinical Hospital #2 of station "Kyiv" of South East Railroad
      • Kyiv, Ukraine, 04050
        • National Medical University n.a. O.O. Bogomolets, Chair of Family Medicine based on Outpatient Clini
      • Odesa, Ukraine, 65039
        • Odessa State Medical University
      • Odesa, Ukraine, 65114
        • Odessa City Policlinic #20
      • Vinnytsya, Ukraine, 21010
        • Vinnytsya Regional Clinical Endocrinology Dispensary
  • United States
    • Alabama
      • Gulf Shores, Alabama, United States, 36542
        • Fundamental Research LLC
    • Alaska
      • Little Rock, Alaska, United States, 72205
        • KLR Business Group dba Arkansas Clinical Research
    • Arizona
      • Chandler, Arizona, United States, 85224
        • Radiant Research, Inc.
      • Phoenix, Arizona, United States, 85020
        • Central Phoenix Medical Clinic
      • Tempe, Arizona, United States, 85282
        • Clinical Research Advantage
      • Tucson, Arizona, United States, 85710
        • Desert Sun Clinical Research, LLC
    • California
      • Los Angeles, California, United States, 90057
        • National Research Institute
      • San Diego, California, United States, 92117
        • Ritchken and First MD's
      • Santa Clarita, California, United States, 91350
        • Clearview Medical Research, LLC
      • Tarzana, California, United States, 91356
        • Metabolic Institute of America
      • Tustin, California, United States, 92780
        • University Clinical Investigators
      • West Hills, California, United States, 91307
        • Infosphere Clinical Research
    • Colorado
      • Colorado Springs, Colorado, United States, 80906
        • Colorado Springs Health Partners
    • Florida
      • Boca Raton, Florida, United States, 33432
        • Boca Raton Clinical Research Associates, Inc.
      • Hallandale Beach, Florida, United States, 33009
        • MD Clinical Institute
      • Hialeah, Florida, United States, 33012
        • A G A Clinical Trials
      • Miami, Florida, United States, 33156
        • Baptist Diabetes Associates
      • Orlando, Florida, United States, 32822
        • Florida Institute For Clinical Research LLC
      • Sanford, Florida, United States, 32771
        • Medical Research Group of Central Florida
    • Georgia
      • Atlanta, Georgia, United States, 30338
        • Perimeter Institute For Clinical Research
      • Atlanta, Georgia, United States, 30312
        • Synergy Therapeutic Partners
      • Columbus, Georgia, United States, 31904
        • Columbus Research Foundation
    • Idaho
      • Boise, Idaho, United States, 83642
        • Advanced Clinical Research
      • Eagle, Idaho, United States, 83616
        • Choose To Lose
    • Illinois
      • Chicago, Illinois, United States, 60607
        • Cedar-Crosse Research Center
    • Louisiana
      • Alexandria, Louisiana, United States, 71301
        • Alexandria Cardiology Clinic
      • Mandeville, Louisiana, United States, 70471
        • Covington Medical Care
      • Metairie, Louisiana, United States, 70006
        • Clinical Trials Management, LLC
    • Maryland
      • Oxon Hill, Maryland, United States, 20745
        • MD Medical Research
    • Nebraska
      • Bellevue, Nebraska, United States, 68005
        • Bellevue Family Practice
    • Nevada
      • Henderson, Nevada, United States, 89052
        • Clinical Research Advantage
    • New Mexico
      • Albuquerque, New Mexico, United States, 87102
        • Albuquerque Clinical Trials, Inc.
      • Albuquerque, New Mexico, United States, 87131-0001
        • University of New Mexico Health Sciences Center
    • North Carolina
      • Greensboro, North Carolina, United States, 27405
        • PhysiqueMed Clinical Trials
      • Hickory, North Carolina, United States, 28601
        • Clinical Trials of America Inc
      • Huntersville, North Carolina, United States, 28078
        • University Medical Associates
      • Lenoir, North Carolina, United States, 28645
        • Northstate Clinical Research
      • Shelby, North Carolina, United States, 28150
        • Carolina Research Center
    • North Dakota
      • Fargo, North Dakota, United States, 58103
        • Lillestol Research
    • Ohio
      • Cleveland, Ohio, United States, 44122
        • Rapid Medical Research, Inc
      • Columbus, Ohio, United States, 43213
        • Columbus Clinical Research Inc.
      • Dayton, Ohio, United States, 45432
        • Hometown Urgent Care and Research
    • Pennsylvania
      • Altoona, Pennsylvania, United States, 16602
        • Blair Medical Associates Inc.
    • Rhode Island
      • East Providence, Rhode Island, United States, 02914
        • Safe Harbor Clinical Research
    • South Carolina
      • Charleston, South Carolina, United States, 29412
        • Pharmacorp Clinical Trials, Inc.
      • Greer, South Carolina, United States, 29651
        • DeGarmo Institute of Medical Research
    • Tennessee
      • Bristol, Tennessee, United States, 37620
        • Holston Medical Group, P.C.
      • Knoxville, Tennessee, United States, 37923
        • New Phase Research & Development
    • Texas
      • Corpus Christi, Texas, United States, 78414
      • Dallas, Texas, United States, 75230
        • Dallas Diabetes and Endocrine Center
      • Houston, Texas, United States, 77081
        • Texas Center for Drug Development, Inc.
      • Houston, Texas, United States, 77055
        • West Houston Clinical Research
      • Houston, Texas, United States, 77074
        • Juno Research, LLC
      • Katy, Texas, United States, 77450
        • Juno Research, LLC
      • Schertz, Texas, United States, 78154
        • Northeast Clinical Research of San Antonio, LLC
      • Sugarland, Texas, United States, 77479
    • Utah
      • Bountiful, Utah, United States, 84010
        • Progressive Clinical Research, LLC
      • Salt Lake City, Utah, United States, 84124
        • Highland Clinical Research
    • Virginia
      • Burke, Virginia, United States, 22015
        • Burke Internal Medicine, Inc.
      • Manassas, Virginia, United States, 20110
        • Manassas Clinical Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Documented history of T2DM
  • Metformin therapy at a stable total daily dose ≥ 1500 mg and ≤ 2550 mg in addition to diet and exercise for ≥ 8 weeks prior to Screening
  • Body mass index (BMI) 25 to 45 kg/m^2, inclusive, at Screening
  • HbA1c within specified ranges at Screening and at the end of the Qualifying Period based on current metformin dose
  • C-peptide ≥ 0.8 ng/mL at Screening
  • Fasting serum glucose (FSG) ≥ 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

Exclusion Criteria:

  • Type 1 diabetes mellitus
  • History of diabetic ketoacidosis, ketosis-prone diabetes, or hyperosmolar hyperglycemic coma
  • History of severe hypoglycemia
  • Any clinically significant cardiovascular or cerebrovascular event ≤ 3 months prior to Screening
  • History of congestive heart failure
  • Corrected QT interval (QTc) > 500 msec by ECG at Screening, a personal or family history of QTc prolongation, congenital long QT syndrome, or individuals who are receiving drugs that prolong the QTc interval, such as Class Ia or Class III antiarrhythmic agents, erythromycin, and certain antipsychotics (eg, ziprasidone)
  • Serum creatinine concentration ≥ 1.5 mg/dL for males or ≥ 1.4 mg/dL for females at Screening
  • Active liver disease and/or significant abnormal liver function defined as aspartate aminotransferase (AST) > 3 x upper limit of the normal range (ULN) and/or alanine aminotransferase (ALT) > 3 x ULN and/or serum total bilirubin > 2.0 mg/dL
  • Use of any non-insulin antihyperglycemic therapy (other than metformin) for more than 14 days (consecutive or not) during the 12 weeks (24 weeks for thiazolidinediones) prior to Screening and/or use of any antihyperglycemic therapy other than metformin, at any dose, at any time during the 4 weeks prior to randomization
  • Treatment with chronic insulin within 24 weeks prior to Screening (except for one temporary period of daily insulin injections no longer than 7 days)
  • Treatment with strong or moderate cytochrome P450 3A (CYP3A) 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 simvastatin or lovastatin at a dose > 20 mg or > 40 mg daily, respectively, within 14 days prior to randomization

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Ranolazine+metformin

Qualifying Period: Participants will receive metformin 1000 mg + placebo to match ranolazine twice daily for either 2 or 8 weeks (dependent on metformin dose and HbA1c level at Screening).

Treatment Period: Participants will receive ranolazine 500 mg + metformin 500 mg + placebo to match metformin twice daily on Days 1 through 7, followed by ranolazine 1000 mg + metformin 500 mg + placebo to match metformin twice daily from Day 8 through Week 24.

Participants are required to maintain their diet and exercise regimen.
Drug: Ranolazine
Ranolazine tablet(s) administered orally
Other Names:
  • Ranexa®
Behavioral: Diet
Participants are instructed to continue the diet regimen prescribed by their physician.
Behavioral: Exercise
Participants are instructed to continue the exercise regimen prescribed by their physician.
Drug: Metformin
Metformin tablet(s) administered orally once daily
Drug: Placebo to match metformin
Placebo to match metformin for the duration of the study
PLACEBO_COMPARATOR: Placebo+metformin

Qualifying Period: Participants will receive metformin 1000 mg + placebo to match ranolazine twice daily for either 2 or 8 weeks (dependent on metformin dose and HbA1c level at Screening).

Treatment Period: Participants will receive metformin 1000 mg + placebo to match ranolazine twice daily through Week 24.

Participants are required to maintain their diet and exercise regimen.
Behavioral: Diet
Participants are instructed to continue the diet regimen prescribed by their physician.
Behavioral: Exercise
Participants are instructed to continue the exercise regimen prescribed by their physician.
Drug: Metformin
Metformin tablet(s) administered orally once daily
Drug: Placebo to match ranolazine
Placebo to match ranolazine for the duration of the study

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24
Time Frame: Baseline; Week 24
The average (mean) change from baseline in HbA1c at Week 24 was analyzed.
Baseline; Week 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Fasting Serum Glucose at Week 24
Time Frame: Baseline; Week 24
The average (mean) change from baseline in fasting serum glucose at Week 24 was analyzed.
Baseline; Week 24
Change From Baseline in 2-hour Postprandial Serum Glucose at Week 24
Time Frame: Baseline; Week 24

The average (mean) change from baseline in 2-hour postprandial serum glucose at Week 24 was analyzed.

Mixed Meal Tolerance Test (MMTT) Full Analysis Set: randomized participants who received at least one dose of study treatment with a baseline and at least one postbaseline measurement of serum glucose at T=120 minutes during the MMTT, administered under fasting conditions, excluding participants with major eligibility protocol violations; analyzed based on the randomized treatment regardless of actual treatment received.
Baseline; Week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gilead Sciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2012

Primary Completion (ACTUAL)

September 1, 2013

Study Completion (ACTUAL)

October 1, 2013

Study Registration Dates

First Submitted

March 13, 2012

First Submitted That Met QC Criteria

March 13, 2012

First Posted (ESTIMATE)

March 15, 2012

Study Record Updates

Last Update Posted (ESTIMATE)

September 23, 2014

Last Update Submitted That Met QC Criteria

September 17, 2014

Last Verified

September 1, 2014

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GS-US-259-0147
  • 2012-001259-37 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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