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

Phase 3

Completed

Conditions: Type 2 Diabetes Mellitus

Interventions: Drug: Ranolazine
Drug: Placebo to match ranolazine
Drug: Metformin
Drug: Placebo to match metformin
Behavioral: Diet
Behavioral: Exercise

Registration Number: NCT01555164

Lead Sponsor: Gilead Sciences

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 442

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ranolazine+metformin	Ranolazine	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.
Ranolazine+metformin	Placebo to match 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.
Ranolazine+metformin	Diet	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.
Ranolazine+metformin	Exercise	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.
Placebo+metformin	Placebo to match ranolazine	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.
Placebo+metformin	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.
Placebo+metformin	Diet	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.
Placebo+metformin	Exercise	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.
Ranolazine+metformin	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.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24	Baseline; Week 24	The average (mean) change from baseline in HbA1c at Week 24 was analyzed.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Fasting Serum Glucose at Week 24	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	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.

Trial Locations

Locations (142): New Phase Research & Development
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Knoxville, Tennessee, United States
National Research Institute
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Los Angeles, California, United States
Baptist Diabetes Associates
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Miami, Florida, United States
Rapid Medical Research, Inc
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Cleveland, Ohio, United States
West Houston Clinical Research
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Houston, Texas, United States
Kovai Diabetes Speciality Centre & Hospital
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Coimbatore, Tamilnadu, India
Jnana Sanjeevani Medical Center
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Bangalore, Karnataka, India
Institue of Clinical Endocrinology (I.C.E) and Diabetes Care Unit (D.C.U),
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Nagpur, Maharashtra, India
Diabetes Care and Research Centre
🇮🇳
Pune, Maharashtra, India
Madras Diabetes Research Foundation
🇮🇳
Chennai, Tamilnadu, India
KEM Hospital Research Center
🇮🇳
Pune, Maharashtra, India
Swamy Diabetes Centre
🇮🇳
Chennai, Tamilnadu, India
Synergy Therapeutic Partners
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Atlanta, Georgia, United States
Medical Research Group of Central Florida
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Sanford, Florida, United States
Cedar-Crosse Research Center
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Chicago, Illinois, United States
Clearview Medical Research, LLC
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Santa Clarita, California, United States
Clinical Research Advantage
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Henderson, Nevada, United States
Bellevue Family Practice
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Bellevue, Nebraska, United States
KLR Business Group DBA Arkansas Clinical Research
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Little Rock, Alaska, United States
Carolina Research Center
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Shelby, North Carolina, United States
A G A Clinical Trials
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Hialeah, Florida, United States
Metabolic Institute of America
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Tarzana, California, United States
Ritchken and First MD's
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San Diego, California, United States
Fundamental Research LLC
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Gulf Shores, Alabama, United States
Infosphere Clinical Research
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West Hills, California, United States
Central Phoenix Medical Clinic
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Phoenix, Arizona, United States
Radiant Research, Inc.
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Chandler, Arizona, United States
Columbus Research Foundation
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Columbus, Georgia, United States
Perimeter Institute for Clinical Research
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Atlanta, Georgia, United States
Albuquerque Clinical Trials, Inc.
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Albuquerque, New Mexico, United States
MD Clinical Institute
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Hallandale Beach, Florida, United States
Colorado Springs Health Partners
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Colorado Springs, Colorado, United States
Advanced Clinical Research
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Boise, Idaho, United States
Alexandria Cardiology Clinic
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Alexandria, Louisiana, United States
University of New Mexico Health Sciences Center
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Albuquerque, New Mexico, United States
Covington Medical Care
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Mandeville, Louisiana, United States
Juno Research, LLC
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Katy, Texas, United States
DeGarmo Institute of Medical Research
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Greer, South Carolina, United States
Pharmacorp Clinical Trials, Inc.
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Charleston, South Carolina, United States
Dallas Diabetes and Endocrine Center
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Dallas, Texas, United States
Columbus Clinical Research Inc.
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Columbus, Ohio, United States
Blair Medical Associates Inc.
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Altoona, Pennsylvania, United States
University Medical Associates
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Huntersville, North Carolina, United States
Texas Center for Drug Development, Inc.
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Houston, Texas, United States
Manassas Clinical Research Center
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Manassas, Virginia, United States
Northeast Clinical Research of San Antonio, LLC
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Schertz, Texas, United States
Dia Care- A Complete Diabetes Care Center
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Ahmadabad, Gujarat, India
Kanizsai Dorottya Hospital
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Nagykanizsa, Hungary
Joanne F. Liutkus Medicine Professional Corporation
🇨🇦
Cambridge, Ontario, Canada
Source Unique Research
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Hawkesbury, Ontario, Canada
Soroka University Medical Center
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Beer Sheva, Israel
Diabetomics India
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Hyderabad, Andhra Pradesh, India
Endocrinology Diabetes Centre
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Bangalore, Karnataka, India
Synexus Hungary Ltd
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Budapest, Hungary
Selye János Kórház és Rendel?intézet, Belgyógyászati Szakrendelés
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Komárom, Hungary
Medifarma 98
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Nyíregyháza, Hungary
Ziv Medical Center Safed-Israel
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Safed, Israel
Alexanders City Hospital
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St. Petersburg, Russian Federation
Clinic of New Medical Technology Company Limited
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Dzerzhinskiy, Russian Federation
Novosibirsk State Medical University
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Novosibirsk, Russian Federation
State Institution of Public Health of Moscow City Endocrinology Dispensary
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Moscow, Russian Federation
Fortis City Centre
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Chandigarh, Punjab, India
Seth G. S. Medical College and KEM Hospital
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Mumbai, Maharashtra, India
Edith Wolfson Medical Center
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Holon, Israel
Kemerovo Regional Clinical Hospital
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Kemerovo, Russian Federation
GOU VPO "Chita State Medical Academy" of Minzdravsocrazvitie RF
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Chita, Russian Federation
Ryazan State Medical University
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Ryazan, Russian Federation
Krestovsky Island Medical Institute, LLC
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St. Petersburg, Russian Federation
Smolensk State Medical Academy, Sanatorium-Preventorium
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Smolensk, Russian Federation
Military Medical Academy named after S.M. Kirov
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St. Petersburg, Russian Federation
East Rand Research Trading as Worthwhile Clinical Trials
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Benoni, South Africa
SPb GBUZ Diagnostic Center #85
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St. Petersburg, Russian Federation
Centre for Diabetes and Endocrinology Suite 1
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Congella, Durban, South Africa
City Hospital named after N.A.Semashko
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Yaroslavl, Russian Federation
Yaroslavl Regional Clinical Hospital
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Yaroslavl, Russian Federation
Netcare Umhlanga Medical Centre
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Kwa Zulu Natal, South Africa
Charlotte Maxeke Johannesburg Academic Hospital
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Johannesburg, South Africa
Drs. Naiker and Naicker Inc.
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Overport, Durban, South Africa
Aliwal Shoal Medical & Clinical Trial Centre
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Kwa Zulu Natal, South Africa
Helderberg Clinical Trials Centre
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Somerset West, South Africa
State Institution "Institute of Problems of Endocrine Pathology n.a. V.Y. Danylevsky of NAMS of Ukra
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Kharkiv, Ukraine
Odessa State Medical University
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Odesa, Ukraine
Administration of Medical Service and Rehabilitation of "ARTEM" State Holding Company
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Kyiv, Ukraine
Synexus Clinical Research SA (Pty) Ltd
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Meyerspark, Pretoria, South Africa
Rostov State Medical University
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Rostov-on-Don, Russian Federation
Reafan, LLC
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Novosibirsk, Russian Federation
Desert Sun Clinical Research, LLC
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Tucson, Arizona, United States
University Clinical Investigators
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Tustin, California, United States
Florida Institute for Clinical Research LLC
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Orlando, Florida, United States
MD Medical Research
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Oxon Hill, Maryland, United States
PhysiqueMed Clinical Trials
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Greensboro, North Carolina, United States
Northstate Clinical Research
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Lenoir, North Carolina, United States
Hometown Urgent Care and Research
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Dayton, Ohio, United States
Holston Medical Group, P.C.
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Bristol, Tennessee, United States
Progressive Clinical Research, LLC
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Bountiful, Utah, United States
Burke Internal Medicine, Inc.
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Burke, Virginia, United States
Borbanya Praxis Kft., Outpatient Clinic
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Nyíregyháza, Hungary
DHL Research Centre, 2nd Floor
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Ahmadabad, Gujarat, India
Getwell Hospital and Research Institute
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Nagpur, Maharashtra, India
Diabetes and Heart Centre
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Ludhiana, Punjab, India
Centrum Terapii Wspolczesnej J.M. Jasnorzewska Sp. Komandytowo - Akcyjna
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Lodz, Lodzkie, Poland
Center "Diabetes", LLC
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Samara, Russian Federation
North-Western State Medical Unversity n.a. I.I.Mechnikov
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St. Petersburg, Russian Federation
City Diabetology Center #4, "City Polyclinic #77"
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St. Petersburg, Russian Federation
Medinet, LLC
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St. Petersburg, Russian Federation
Saint-Petersburg City Outpatient Clinic#37
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St. Petersburg, Russian Federation
Clinical Hospital #122 n.a. Sokolov of FMBA
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St. Petersburg, Russian Federation
ANO Medical Centre XXI Century
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St. Petersburg, Russian Federation
City Hospital #38 named after N. A. Semashko
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St. Petersburg, Russian Federation
Federal Centre of Heart, Blood and Endocrinology named after V.A. Almazov
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St. Petersburg, Russian Federation
Federal State Budget Military Educational Institution Medical Military Academy n. a. S. M. Kirov
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St. Petersburg, Russian Federation
Vawda Z Private Practice
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Kwa Zulu Natal, Durban, South Africa
Newkwa Medical Centre
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Newlands West, Durban, South Africa
Ukrainian Scientific-and-Practical Center of Endocrine Surgery, Transplantation of Endocrine Organs
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Kyiv, Ukraine
National Medical University n.a. O.O. Bogomolets, Chair of Family Medicine based on Outpatient Clini
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Kyiv, Ukraine
Clinical Trials Management, LLC
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Metairie, Louisiana, United States
Highland Clinical Research
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Salt Lake City, Utah, United States
Boca Raton Clinical Research Associates, Inc.
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Boca Raton, Florida, United States
Clinical Trials of America Inc
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Hickory, North Carolina, United States
Choose To Lose
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Eagle, Idaho, United States
Lillestol Research
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Fargo, North Dakota, United States
Safe Harbor Clinical Research
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East Providence, Rhode Island, United States
The Bangalore Diabetes Hospital
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Bangalore, Karnataka, India
LANDA - Specjalistyczne Gabinety Lekarskie
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Krakow, Malopolskie, Poland
Educational Scientific Medical Centre, Donetsk National Medical University
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Donetsk, Ukraine
V. P. Komissarenko Institute of Endocrinology and Metabolism of AMS of Ukraine
🇺🇦
Kyiv, Ukraine
Odessa City Policlinic #20
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Odesa, Ukraine
Vinnytsya Regional Clinical Endocrinology Dispensary
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Vinnytsya, Ukraine
Diabetes Research Clinic
🇨🇦
Vancouver, British Columbia, Canada
Restrial s.r.o.
🇨🇿
Praha 8, Praha, Czech Republic
Endocrinology & Diabetes Research Centre
🇮🇳
Bangalore, Karnataka, India
Manipal Hospital
🇮🇳
Bangalore, Karnataka, India
The Medical Arts Health Research Group
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Kelowna, British Columbia, Canada
Baroda Medical College and SSG Hospital
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Vadodara, Gujarat, India
Banker's Heart Institute
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Vadodara, Gujarat, India
Nemocnice s poliklinikou Havirov
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Havirov, Moravskoslezsky kraj, Czech Republic
Bangalore Diabetes Hospital
🇮🇳
Bangalore, Karnataka, India
Vinaya Hospital and Research Centre
🇮🇳
Mangalore, Karnataka, India
NZOZ "Esculap" S.C.
🇵🇱
Gniewkowo, Poland
Niepubliczy Zaklad Opieki Zdrowotnej (NZOZ) Specjalistyczny Osrodek Internistyczno - Diabetologiczny
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Bialystok, Poland
Department of Endocrinology of Railway Clinical Hospital #2 of station "Kyiv" of South East Railroad
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Kyiv, Ukraine
Instituto Jalisciense de Investigación en Diabetes y Obesidad
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Guadalajara, Jalisco, Mexico