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

This study has been completed.
Information provided by (Responsible Party):
Gilead Sciences Identifier:
First received: March 13, 2012
Last updated: September 17, 2014
Last verified: September 2014
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.

Condition Intervention Phase
Type 2 Diabetes Mellitus Drug: Ranolazine Drug: Placebo to match ranolazine Drug: Metformin Drug: Placebo to match metformin Behavioral: Diet Behavioral: Exercise Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:

Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • 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.

Secondary Outcome Measures:
  • 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.

  • 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.

Enrollment: 442
Study Start Date: June 2012
Study Completion Date: October 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Ranexa®
Drug: Metformin
Metformin tablet(s) administered orally once daily
Drug: Placebo to match metformin
Placebo to match metformin for the duration of the study
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.
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.

Drug: Placebo to match ranolazine
Placebo to match ranolazine for the duration of the study
Drug: Metformin
Metformin tablet(s) administered orally once daily
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.


Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01555164

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

Responsible Party: Gilead Sciences Identifier: NCT01555164     History of Changes
Other Study ID Numbers: GS-US-259-0147
2012-001259-37 ( EudraCT Number )
Study First Received: March 13, 2012
Results First Received: September 17, 2014
Last Updated: September 17, 2014

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Hypoglycemic Agents
Physiological Effects of Drugs
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action processed this record on September 21, 2017