Clinical trial NCT01555164: A Phase 3 Study of Ranolazine in Subjects With Type 2 Diabetes Who Are Inadequately Controlled on Metformin Alone
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2012-03-15
Enrollment: 442
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24
timeFrame: Baseline; Week 24
Secondary outcomes:
measure: Change From Baseline in Fasting Serum Glucose at Week 24
timeFrame: Baseline; Week 24
measure: Change From Baseline in 2-hour Postprandial Serum Glucose at Week 24
timeFrame: Baseline; Week 24
Other outcomes:
Locations:
city: Gulf Shores
country: United States
facility: Fundamental Research LLC
state: Alabama
city: Little Rock
country: United States
facility: KLR Business Group DBA Arkansas Clinical Research
state: Alaska
city: Chandler
country: United States
facility: Radiant Research, Inc.
state: Arizona
city: Phoenix
country: United States
facility: Central Phoenix Medical Clinic
state: Arizona
city: Tempe
country: United States
facility: Clinical Research Advantage
state: Arizona
city: Tucson
country: United States
facility: Desert Sun Clinical Research, LLC
state: Arizona
city: Los Angeles
country: United States
facility: National Research Institute
state: California
city: San Diego
country: United States
facility: Ritchken and First MD's
state: California
city: Santa Clarita
country: United States
facility: Clearview Medical Research, LLC
state: California
city: Tarzana
country: United States
facility: Metabolic Institute of America
state: California
city: Tustin
country: United States
facility: University Clinical Investigators
state: California
city: West Hills
country: United States
facility: Infosphere Clinical Research
state: California
city: Colorado Springs
country: United States
facility: Colorado Springs Health Partners
state: Colorado
city: Boca Raton
country: United States
facility: Boca Raton Clinical Research Associates, Inc.
state: Florida
city: Hallandale Beach
country: United States
facility: MD Clinical Institute
state: Florida
city: Hialeah
country: United States
facility: A G A Clinical Trials
state: Florida
city: Miami
country: United States
facility: Baptist Diabetes Associates
state: Florida
city: Orlando
country: United States
facility: Florida Institute for Clinical Research LLC
state: Florida
city: Sanford
country: United States
facility: Medical Research Group of Central Florida
state: Florida
city: Atlanta
country: United States
facility: Synergy Therapeutic Partners
state: Georgia
city: Atlanta
country: United States
facility: Perimeter Institute for Clinical Research
state: Georgia
city: Columbus
country: United States
facility: Columbus Research Foundation
state: Georgia
city: Boise
country: United States
facility: Advanced Clinical Research
state: Idaho
city: Eagle
country: United States
facility: Choose To Lose
state: Idaho
city: Chicago
country: United States
facility: Cedar-Crosse Research Center
state: Illinois
city: Alexandria
country: United States
facility: Alexandria Cardiology Clinic
state: Louisiana
city: Mandeville
country: United States
facility: Covington Medical Care
state: Louisiana
city: Metairie
country: United States
facility: Clinical Trials Management, LLC
state: Louisiana
city: Oxon Hill
country: United States
facility: MD Medical Research
state: Maryland
city: Bellevue
country: United States
facility: Bellevue Family Practice
state: Nebraska
city: Henderson
country: United States
facility: Clinical Research Advantage
state: Nevada
city: Albuquerque
country: United States
facility: Albuquerque Clinical Trials, Inc.
state: New Mexico
city: Albuquerque
country: United States
facility: University of New Mexico Health Sciences Center
state: New Mexico
city: Greensboro
country: United States
facility: PhysiqueMed Clinical Trials
state: North Carolina
city: Hickory
country: United States
facility: Clinical Trials of America Inc
state: North Carolina
city: Huntersville
country: United States
facility: University Medical Associates
state: North Carolina
city: Lenoir
country: United States
facility: Northstate Clinical Research
state: North Carolina
city: Shelby
country: United States
facility: Carolina Research Center
state: North Carolina
city: Fargo
country: United States
facility: Lillestol Research
state: North Dakota
city: Cleveland
country: United States
facility: Rapid Medical Research, Inc
state: Ohio
city: Columbus
country: United States
facility: Columbus Clinical Research Inc.
state: Ohio
city: Dayton
country: United States
facility: Hometown Urgent Care and Research
state: Ohio
city: Altoona
country: United States
facility: Blair Medical Associates Inc.
state: Pennsylvania
city: East Providence
country: United States
facility: Safe Harbor Clinical Research
state: Rhode Island
city: Charleston
country: United States
facility: Pharmacorp Clinical Trials, Inc.
state: South Carolina
city: Greer
country: United States
facility: DeGarmo Institute of Medical Research
state: South Carolina
city: Bristol
country: United States
facility: Holston Medical Group, P.C.
state: Tennessee
city: Knoxville
country: United States
facility: New Phase Research & Development
state: Tennessee
city: Corpus Christi
country: United States
state: Texas
city: Dallas
country: United States
facility: Dallas Diabetes and Endocrine Center
state: Texas
city: Houston
country: United States
facility: West Houston Clinical Research
state: Texas
city: Houston
country: United States
facility: Juno Research, LLC
state: Texas
city: Houston
country: United States
facility: Texas Center for Drug Development, Inc.
state: Texas
city: Katy
country: United States
facility: Juno Research, LLC
state: Texas
city: Schertz
country: United States
facility: Northeast Clinical Research of San Antonio, LLC
state: Texas
city: Sugarland
country: United States
state: Texas
city: Bountiful
country: United States
facility: Progressive Clinical Research, LLC
state: Utah
city: Salt Lake City
country: United States
facility: Highland Clinical Research
state: Utah
city: Burke
country: United States
facility: Burke Internal Medicine, Inc.
state: Virginia
city: Manassas
country: United States
facility: Manassas Clinical Research Center
state: Virginia
city: Kelowna
country: Canada
facility: The Medical Arts Health Research Group
state: British Columbia
city: Vancouver
country: Canada
facility: Diabetes Research Clinic
state: British Columbia
city: Cambridge
country: Canada
facility: Joanne F. Liutkus Medicine Professional Corporation
state: Ontario
city: Hawkesbury
country: Canada
facility: Source Unique Research
state: Ontario
city: Havirov
country: Czech Republic
facility: Nemocnice s poliklinikou Havirov
state: Moravskoslezsky kraj
city: Praha 8
country: Czech Republic
facility: Restrial s.r.o.
state: Praha
city: Budapest
country: Hungary
facility: Synexus Hungary Ltd
city: Komárom
country: Hungary
facility: Selye János Kórház és Rendel?intézet, Belgyógyászati Szakrendelés
city: Nagykanizsa
country: Hungary
facility: Kanizsai Dorottya Hospital
city: Nyíregyháza
country: Hungary
facility: Medifarma 98
city: Nyíregyháza
country: Hungary
facility: Borbanya Praxis Kft., Outpatient Clinic
city: Hyderabad
country: India
facility: Diabetomics India
state: Andhra Pradesh
city: Ahmadabad
country: India
facility: DHL Research Centre, 2nd Floor
state: Gujarat
city: Ahmadabad
country: India
facility: Dia Care- A Complete Diabetes Care Center
state: Gujarat
city: Vadodara
country: India
facility: Baroda Medical College and SSG Hospital
state: Gujarat
city: Vadodara
country: India
facility: Banker's Heart Institute
state: Gujarat
city: Bangalore
country: India
facility: Endocrinology & Diabetes Research Centre
state: Karnataka
city: Bangalore
country: India
facility: Manipal Hospital
state: Karnataka
city: Bangalore
country: India
facility: Endocrinology Diabetes Centre
state: Karnataka
city: Bangalore
country: India
facility: Bangalore Diabetes Hospital
state: Karnataka
city: Bangalore
country: India
facility: The Bangalore Diabetes Hospital
state: Karnataka
city: Bangalore
country: India
facility: Jnana Sanjeevani Medical Center
state: Karnataka
city: Mangalore
country: India
facility: Vinaya Hospital and Research Centre
state: Karnataka
city: Mumbai
country: India
facility: Seth G. S. Medical College and KEM Hospital
state: Maharashtra
city: Nagpur
country: India
facility: Institue of Clinical Endocrinology (I.C.E) and Diabetes Care Unit (D.C.U),
state: Maharashtra
city: Nagpur
country: India
facility: Getwell Hospital and Research Institute
state: Maharashtra
city: Pune
country: India
facility: Diabetes Care and Research Centre
state: Maharashtra
city: Pune
country: India
facility: KEM Hospital Research Center
state: Maharashtra
city: Chandigarh
country: India
facility: Fortis City Centre
state: Punjab
city: Ludhiana
country: India
facility: Diabetes and Heart Centre
state: Punjab
city: Chennai
country: India
facility: Swamy Diabetes Centre
state: Tamilnadu
city: Chennai
country: India
facility: Madras Diabetes Research Foundation
state: Tamilnadu
city: Coimbatore
country: India
facility: Kovai Diabetes Speciality Centre & Hospital
state: Tamilnadu
city: Beer Sheva
country: Israel
facility: Soroka University Medical Center
city: Holon
country: Israel
facility: Edith Wolfson Medical Center
city: Safed
country: Israel
facility: Ziv Medical Center Safed-Israel
city: Guadalajara
country: Mexico
facility: Instituto Jalisciense de Investigación en Diabetes y Obesidad
state: Jalisco
city: Lodz
country: Poland
facility: Centrum Terapii Wspolczesnej J.M. Jasnorzewska Sp. Komandytowo - Akcyjna
state: Lodzkie
city: Krakow
country: Poland
facility: LANDA - Specjalistyczne Gabinety Lekarskie
state: Malopolskie
city: Bialystok
country: Poland
facility: Niepubliczy Zaklad Opieki Zdrowotnej (NZOZ) Specjalistyczny Osrodek Internistyczno - Diabetologiczny
city: Gniewkowo
country: Poland
facility: NZOZ "Esculap" S.C.
city: Chita
country: Russian Federation
facility: GOU VPO "Chita State Medical Academy" of Minzdravsocrazvitie RF
city: Dzerzhinskiy
country: Russian Federation
facility: Clinic of New Medical Technology Company Limited
city: Kemerovo
country: Russian Federation
facility: Kemerovo Regional Clinical Hospital
city: Moscow
country: Russian Federation
facility: State Institution of Public Health of Moscow City Endocrinology Dispensary
city: Novosibirsk
country: Russian Federation
facility: Novosibirsk State Medical University
city: Novosibirsk
country: Russian Federation
facility: Reafan, LLC
city: Rostov-on-Don
country: Russian Federation
facility: Rostov State Medical University
city: Ryazan
country: Russian Federation
facility: Ryazan State Medical University
city: Samara
country: Russian Federation
facility: Center "Diabetes", LLC
city: Smolensk
country: Russian Federation
facility: Smolensk State Medical Academy, Sanatorium-Preventorium
city: St. Petersburg
country: Russian Federation
facility: Medinet, LLC
city: St. Petersburg
country: Russian Federation
facility: North-Western State Medical Unversity n.a. I.I.Mechnikov
city: St. Petersburg
country: Russian Federation
facility: Saint-Petersburg City Outpatient Clinic#37
city: St. Petersburg
country: Russian Federation
facility: Military Medical Academy named after S.M. Kirov
city: St. Petersburg
country: Russian Federation
facility: City Diabetology Center #4, "City Polyclinic #77"
city: St. Petersburg
country: Russian Federation
facility: Alexanders City Hospital
city: St. Petersburg
country: Russian Federation
facility: Clinical Hospital #122 n.a. Sokolov of FMBA
city: St. Petersburg
country: Russian Federation
facility: ANO Medical Centre XXI Century
city: St. Petersburg
country: Russian Federation
facility: City Hospital #38 named after N. A. Semashko
city: St. Petersburg
country: Russian Federation
facility: Krestovsky Island Medical Institute, LLC
city: St. Petersburg
country: Russian Federation
facility: Federal Centre of Heart, Blood and Endocrinology named after V.A. Almazov
city: St. Petersburg
country: Russian Federation
facility: Federal State Budget Military Educational Institution Medical Military Academy n. a. S. M. Kirov
city: St. Petersburg
country: Russian Federation
facility: SPb GBUZ Diagnostic Center #85
city: Yaroslavl
country: Russian Federation
facility: City Hospital named after N.A.Semashko
city: Yaroslavl
country: Russian Federation
facility: Yaroslavl Regional Clinical Hospital
city: Congella
country: South Africa
facility: Centre for Diabetes and Endocrinology Suite 1
state: Durban
city: Kwa Zulu Natal
country: South Africa
facility: Vawda Z Private Practice
state: Durban
city: Newlands West
country: South Africa
facility: Newkwa Medical Centre
state: Durban
city: Overport
country: South Africa
facility: Drs. Naiker and Naicker Inc.
state: Durban
city: Meyerspark
country: South Africa
facility: Synexus Clinical Research SA (Pty) Ltd
state: Pretoria
city: Benoni
country: South Africa
facility: East Rand Research Trading as Worthwhile Clinical Trials
city: Johannesburg
country: South Africa
facility: Charlotte Maxeke Johannesburg Academic Hospital
city: Kwa Zulu Natal
country: South Africa
facility: Aliwal Shoal Medical & Clinical Trial Centre
city: Kwa Zulu Natal
country: South Africa
facility: Netcare Umhlanga Medical Centre
city: Somerset West
country: South Africa
facility: Helderberg Clinical Trials Centre
city: Donetsk
country: Ukraine
facility: Educational Scientific Medical Centre, Donetsk National Medical University
city: Kharkiv
country: Ukraine
facility: State Institution "Institute of Problems of Endocrine Pathology n.a. V.Y. Danylevsky of NAMS of Ukra
city: Kyiv
country: Ukraine
facility: Ukrainian Scientific-and-Practical Center of Endocrine Surgery, Transplantation of Endocrine Organs
city: Kyiv
country: Ukraine
facility: Department of Endocrinology of Railway Clinical Hospital #2 of station "Kyiv" of South East Railroad
city: Kyiv
country: Ukraine
facility: Administration of Medical Service and Rehabilitation of "ARTEM" State Holding Company
city: Kyiv
country: Ukraine
facility: National Medical University n.a. O.O. Bogomolets, Chair of Family Medicine based on Outpatient Clini
city: Kyiv
country: Ukraine
facility: V. P. Komissarenko Institute of Endocrinology and Metabolism of AMS of Ukraine
city: Odesa
country: Ukraine
facility: Odessa State Medical University
city: Odesa
country: Ukraine
facility: Odessa City Policlinic #20
city: Vinnytsya
country: Ukraine
facility: Vinnytsya Regional Clinical Endocrinology Dispensary
Study officials:
affiliation: Gilead Sciences
name: Patrick Yue, MD
role: STUDY_DIRECTOR
References: