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

Type 2 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01555164
• Other study ID #: GS-US-259-0147
• Secondary ID: 2012-001259-37
• Status: Completed
• Phase: Phase 3
• First received: March 13, 2012
• Last updated: September 17, 2014
• Start date: June 2012
• Est. completion date: October 2013

Study information

• Verified date: September 2014
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health CanadaRussia: Ministry of Health of the Russian FederationUkraine: Ministry of HealthCzech Republic: State Institute for Drug ControlPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsRomania: National Agency for Medicines and Medical DevicesIndia: Drugs Controller General of IndiaIsrael: Ministry of HealthSouth Africa: Medicines Control CouncilSouth Korea: Korea Food and Drug Administration (KFDA)Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaMexico: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 442
• Est. completion date: October 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Canada,  Czech Republic,  Hungary,  India,  Israel,  Mexico,  Poland,  Russian Federation,  South Africa,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Change From Baseline in Fasting Serum Glucose at Week 24	The average (mean) change from baseline in fasting serum glucose at Week 24 was analyzed.	Baseline; Week 24	No
Secondary	Change From Baseline in 2-hour Postprandial Serum Glucose at 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	No