Ranolazine When Added to Glimepiride in Subjects With Type 2 Diabetes Mellitus
NCT ID: NCT01494987
Last Updated: 2014-11-18
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE3
431 participants
INTERVENTIONAL
2012-01-31
2013-08-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
DOUBLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Ranolazine+glimepiride
Glimepiride stabilization period (up to 8 weeks): participants not on stable glimepiride will receive glimepiride 2 mg once daily, and if tolerated the dose will be increased on Day 8 (+ 2 days) to 4 mg once daily.
Qualifying period: participants will receive placebo to match ranolazine twice daily in addition to glimepiride for 14 days (+ 2 days) and if ≥ 80% compliant and meeting eligibility criteria will continue to the treatment period.
Treatment period: participants will be randomized to receive ranolazine 500 mg twice daily plus glimepiride 4 mg once daily on Days 1 through 7, followed by ranolazine 1000 mg twice daily plus glimepiride 4 mg once daily from Day 8 (or by Day 16 if not well tolerated) through Week 24.
Participants will be required to maintain their diet and exercise regimen.
Ranolazine
Ranolazine tablet(s) administered orally
Glimepiride
Glimepiride tablets (2 mg or 4 mg) administered orally once daily with the morning dose of study drug or placebo. The target dosing regimen for glimepiride is 4 mg once daily.
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.
Placebo+glimepiride
Glimepiride stabilization period (up to 8 weeks): participants not on stable glimepiride will receive glimepiride 2 mg once daily, and if tolerated the dose will be increased on Day 8 (+ 2 days) to 4 mg once daily.
Qualifying period: participants will receive placebo to match ranolazine twice daily in addition to glimepiride for 14 days (+ 2 days) and if ≥ 80% compliant and meeting eligibility criteria will continue to the treatment period.
Treatment period: participants will be randomized to receive placebo to match ranolazine plus glimepiride 4 mg once daily for 24 weeks.
Participants will be required to maintain their diet and exercise regimen.
Placebo
Placebo to match ranolazine for the duration of the study
Glimepiride
Glimepiride tablets (2 mg or 4 mg) administered orally once daily with the morning dose of study drug or placebo. The target dosing regimen for glimepiride is 4 mg once daily.
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.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Ranolazine
Ranolazine tablet(s) administered orally
Placebo
Placebo to match ranolazine for the duration of the study
Glimepiride
Glimepiride tablets (2 mg or 4 mg) administered orally once daily with the morning dose of study drug or placebo. The target dosing regimen for glimepiride is 4 mg once daily.
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.
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Males and females, 18 to 75 years old, inclusive
* Documented history of T2DM
* Receiving one of the following sulfonylurea or metformin therapies in addition to diet and exercise for at least 90 days prior to Screening:
1. glimepiride at a daily dose of ≥ 2 mg and ≤ 4 mg
2. glipizide, glyburide, or glibenclamide (or equivalent) at a daily dose of ≥ 7.5 mg
3. gliclazide at a daily dose of \> 160 mg (or ≥ 60 mg for the modified release \[MR\] formulation)
4. metformin at a daily dose of ≥ 1500 mg
* Body mass index (BMI) 25 kg/m2 to 45 kg/m2, inclusive, at Screening
* HbA1c 7% to 10%, inclusive, at Screening and the end of the Qualifying Period (Day 14)
* Fasting Serum 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 (Day 14): A one-time central laboratory re-test of FSG is allowed in subjects with an initial central laboratory FSG ≥ 120 mg/dL (6.7 mmol/L) and \< 130 mg/dL (7.2 mmol/L) who are otherwise eligible as determined by the investigator.
* Able and willing to comply with all study procedures during the course of the study
* Females of child-bearing potential must have a negative serum pregnancy test at Screening and must agree to use highly effective contraception methods from Screening throughout the duration of the Treatment Period and for 14 days following the last dose of study drug.
* At least 80% compliant in dosing during the Qualifying Period
Exclusion Criteria
* History of diabetic ketoacidosis, ketosis-prone diabetes, or hyperosmolar hyperglycemic coma
* History of a severe episode of hypoglycemia (≥ 1 episode within 3 months prior to Screening or ≥ 2 episodes within 6 months prior to Screening), defined as hypoglycemia requiring 3rd party assistance to actively administer carbohydrate, glucagon, or other resuscitative actions due to severe impairment in consciousness or behavior
* Clinically significant complications of diabetes that in the judgment of the investigator would make the subject unsuitable to participate in this study
* History of any clinically significant cardiovascular (CV) or cerebrovascular event (eg, myocardial infarction \[MI\], acute coronary syndrome \[ACS\], recent revascularization \[including coronary artery bypass graft procedures or percutaneous coronary intervention\], transient ischemic attack, or ischemic stroke) ≤ 3 months prior to Screening
* Inadequately controlled or unstable hypertension as defined by a systolic blood pressure (SBP) \> 160 mmHg or diastolic blood pressure (DBP) \> 100 mmHg at Screening and at Randomization
* Prolonged QT interval corrected for heart rate (QTc) interval \> 500 msec by electrocardiogram (ECG) at Screening, a personal or family history of QTc prolongation, congenital long QT syndrome, or subjects who are receiving drugs that prolong the QTc interval, such as Class Ia or Class III antiarrhythmic agents, erythromycin, and certain antipsychotics (eg, ziprasidone)
* History of bariatric surgery at any time in the past or or any other surgery \< 2 months before Screening; or planning to undergo surgery during the study. Subjects with a planned minor surgery may be enrolled upon approval by the medical monitor.
* Any other hospitalization in the 14 days prior to Screening or planned hospitalization at any time during the study
* Significant weight change (± 5%) \< 2 months prior to Screening or enrollment in a weight-loss program other than a maintenance phase at Screening.
* Severe renal impairment, defined as an estimated glomerular filtration rate (eGFR) by the Modification of Diet in Renal Disease (MDRD) equation \< 30 mL/min/1.73 m2 at Screening or undergoing any type of dialysis at Screening or planning to undergo any type of dialysis during the course of the study
* History of liver cirrhosis (Child-Pugh Class A, B or C)
* 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
* History of cancer (except nonmelanomic skin cancers or cervical in situ) within 5 years prior to Screening
* History of alcohol or other drug abuse \< 12 months prior to Screening
* Any other clinically significant existing medical or psychiatric condition, including clinically significant laboratory abnormalities, or one requiring further evaluation that in the opinion of the investigator could interfere with conduct of the study or interpretation of the data
* Use of antihyperglycemic agents other than sulfonylurea agents or metformin, including but not limited to dipeptidyl peptidase-4 inhibitors (eg, saxagliptin and sitagliptin), glucagon-like peptide-mimetics (eg, exenatide), or insulin \< 3 months prior to Screening; use of thiazolidinediones (TZDs) (eg, rosiglitazone or pioglitazone) \< 24 weeks prior to Screening
* Previous history of intolerance of glimepiride (as a single-agent therapy)
* Prior treatment with open-label ranolazine, or known hypersensitivity or intolerance to ranolazine or any of its excipients
* Treatment with strong or moderate cytochrome P (CYP)3A 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 CYP3A4 substrates with a narrow therapeutic range (eg, cyclosporine, tacrolimus, or sirolimus) within 14 days prior to Randomization
* Treatment with simvastatin at a dose of \> 20 mg daily or lovastatin at a dose of \> 40 mg daily within 14 days prior to Randomization
* Weight loss medication or anti-obesity medication (prescription or non-prescription) \< 3 months prior to Screening
* Treatment with niacin \> 200 mg daily; if receiving ≤ 200 mg daily, should be on stable doses for ≥ 3 months prior to Screening
* Expected or current treatment with systemic corticosteroids (oral or injectable) for \> 14 days from Screening through the end of the Treatment Period. Topical or inhaled corticosteroid formulations are permitted at any time during the study.
* If receiving thyroid replacement therapy, should be on stable doses for at least 6 weeks prior to randomization
* Hemoglobin \< 12 g/dL for males or \< 11 g/dL for females at Screening
* Participation in another clinical study involving an investigational drug or device \< 30 days prior to Screening; participation in another clinical study involving an oral antihyperglycemic agent (OHA) \< 90 days prior to Screening
* Donation of blood \< 2 months prior to Screening or plans to donate blood while participating in the study
* Females who are pregnant or are breastfeeding
* Other condition(s) that, in the opinion of the investigator, would compromise the safety of the individual, prevent compliance with the study protocol (including the ability to comply with Mixed Meal Tolerance Test \[MMTT\]), or compromise the quality of the clinical study
18 Years
75 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Gilead Sciences
INDUSTRY
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Patrick Yue, MD
Role: STUDY_DIRECTOR
Gilead Sciences
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Clinical Research Advantage/Desert Clinical Research, LLC
Mesa, Arizona, United States
Desert Sun Clinical Research, LLC
Tucson, Arizona, United States
Eclipse Clinical Research
Tucson, Arizona, United States
Paul W. Davis, MD, PA
Pine Bluff, Arkansas, United States
Southland Clinical Research Center, Inc.
Fountain Valley, California, United States
Valley Research
Fresno, California, United States
Del Rosario Medical Clinic, Inc.
Huntington Park, California, United States
Scripps Whittier Diabetes Institute
La Jolla, California, United States
National Research Institute
Los Angeles, California, United States
Spectrum Clinical Research Institute, Inc
Moreno Valley, California, United States
Sacramento Heart and Vascular Medical Associates
Sacramento, California, United States
Infosphere Clinical Research
West Hills, California, United States
PAB Clinical Research
Brandon, Florida, United States
Florida Research Network, LLC
Gainesville, Florida, United States
NewPhase Clinical Trials, Inc.
Miami Beach, Florida, United States
Suncoast Clinical Research
New Port Richey, Florida, United States
Regenerate Clinical Trials
South Miami, Florida, United States
Comprehensive Clinical Development, Inc.
St. Petersburg, Florida, United States
Clinical Research of Central Florida
Winter Haven, Florida, United States
Synergy Therapeutic Partners
Atlanta, Georgia, United States
CTL Research
Eagle, Idaho, United States
Cedar-Crosse Research Center
Chicago, Illinois, United States
LaPorte County Institute for Clinical Research
Michigan City, Indiana, United States
L-MARC Research Center
Louisville, Kentucky, United States
Horizon Research Group of Opelousas
Eunice, Louisiana, United States
MD Medical Research
Oxon Hill, Maryland, United States
IRC Clinics, Inc
Towson, Maryland, United States
Endeavor Medical Research, PLC
Alpena, Michigan, United States
Associated Internal Medicine Specialists, P.C.
Battle Creek, Michigan, United States
Albuquerque Clinical Trials
Albuquerque, New Mexico, United States
PMG Research of Charlotte
Charlotte, North Carolina, United States
PharmQuest
Greensboro, North Carolina, United States
Clinical Inquest Center, Ltd.
Beavercreek, Ohio, United States
Infinity Research Group, LLC
Oklahoma City, Oklahoma, United States
Southeastern Research Associates, Inc.
Taylors, South Carolina, United States
HCCA Clinical Research Solution
Franklin, Tennessee, United States
Holston Medical Group
Kingsport, Tennessee, United States
New Phase Research & Development
Knoxville, Tennessee, United States
The University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, United States
Excel Clinical Research, LLC
Houston, Texas, United States
Texas Center for Drug Development, Inc.
Houston, Texas, United States
Humble Cardiology Associates
Humble, Texas, United States
Cetero Research
San Antonio, Texas, United States
Cetero Research
San Antonio, Texas, United States
Highland Clinical Research
Salt Lake City, Utah, United States
Jean Brown Research
Salt Lake City, Utah, United States
Interni oddeleni
Havířov, Moravskoslezský kraj, Czechia
Drug Research Center
Balatonfüred, , Hungary
Synexus Hungary Ltd
Budapest, , Hungary
Markhot Ferenc Hospital
Eger, , Hungary
Kanizsai Dorottya Hospital
Nagykanizsa, , Hungary
Borbanya Praxis Kft., Outpatient Clinic
Nyíregyháza, , Hungary
Medifarma 98
Nyíregyháza, , Hungary
Hospital Universiti Sains Malaysia
Kubang Kerian, Kelantan, Malaysia
NZOZ Centrum Badan Klinicznych
Wroclaw, Lower Silesian Voivodeship, Poland
Centrum Badan Klinicznych PI-House Sp. z o.o.
Gdansk, Pomeranian Voivodeship, Poland
LANDA - Specjalistyczne Gabinety Lekarskie
Krakow, , Poland
SPZOZ Uniwersytecki Szpital Kliniczny Nr 1 im. Norberta Barlickiego Uniwersytetu Medycznego w Łodzi, Oddział Kliniczny Diabetologii
Lodz, , Poland
NZOZ Centrum Badan Klinicznych Oswiecim
Oswięcim, , Poland
Centrum Terapii Wspolczesnej J.M. Jasnorzewska Sp. Komandytowo - Akcyjna
Lodz, Łódź Voivodeship, Poland
NZOZ Centrum Medyczne Szpital Sw. Rodziny
Lodz, Łódź Voivodeship, Poland
NZOZ Polimedica
Zgierz, Łódź Voivodeship, Poland
CMI Morosanu V. Magdalena
Galati, Galați County, Romania
Spital Clinic Judetean de Urgenta Oradea Stationarul 1
Oradea, Jud Bihor, Romania
Consultmed SRL
Iași, Jud. Iasi, Romania
Centru Medical Dr. Negrisanu
Timișoara, Judical Timis, Romania
Institutul de Diabet, Nutritie si Boli Metabolice "Dr. N. C. Paulescu"
Bucharest, , Romania
Tehnomed Trading Srl
Bucharest, , Romania
Institutul National De Diabet, Nutritie Si Boli Metabolice "Prof. Dr. N.C. Paulescu"
Bucharest, , Romania
O.D. Medica Srl
Bucharest, , Romania
CMI Mateescu S. Ana-Maria
Constanța, , Romania
Spitalul Clinic Judetean de Urgenta "Sf. Apostol Andrei" Galati
Galati, , Romania
Diabmed Dr. Popescu Alexandrina SRL
Ploieşti, , Romania
3rd Central Military Clinical Hospital named after A.A.Vishnevskogo
Arkhangel'skoye, , Russia
GOU VPO "Chita State Medical Academy" of Minzdravsocrazvitie RF
Chita, , Russia
"Clinic of New Medical Technology" Company Limited
Dzerzhinskiy, , Russia
Kemerovo Regional Clinical Hospital
Kemerovo, , Russia
"Krasnoyarsk State Medical University n.a. Prof. V.F. Voyno-Yasenetsky
Krasnoyarsk, , Russia
State Healthcare Institution of Moscow "Cardiologival Dispensary #2 of Management Department of South Administrative District"
Moscow, , Russia
Central Clinical Hospital of Russian Academy of Sciences
Moscow, , Russia
Medical Sanitary Unit of Minestry of Internal Affairs of Russia in Moscow
Moscow, , Russia
City Clinical Hospital # 13 of Avtozavodsky District of Nizhniy Novgorod
Nizhny Novgorod, , Russia
Novosibirsk State Medical University
Novosibirsk, , Russia
Scientific Research Institute of Physiology of Siberian Department RAMS
Novosibirsk, , Russia
City Hospital # 38 named after N A Semashko
Pushkin, , Russia
Rostov State Medical University
Rostov-on-Don, , Russia
Ryazan State Medical University
Ryazan, , Russia
Medinet, LLC
Saint Petersburg, , Russia
North-Western State Medical Unversity n.a. I.I.Mechnikov
Saint Petersburg, , Russia
Saint-Petersburg City Outpatient Clinic#37
Saint Petersburg, , Russia
Military Medical Academy named after S.M. Kirov
Saint Petersburg, , Russia
Saint-Petersburg state budgetary healthcare institution "City Polyclinic #109"
Saint Petersburg, , Russia
Alexanders City Hospital
Saint Petersburg, , Russia
Clinical Hospital #122 n.a. Sokolov of FMBA
Saint Petersburg, , Russia
ANO "Medical Centre "XXI century"
Saint Petersburg, , Russia
St. Elizabeth City Hospital
Saint Petersburg, , Russia
Krestovsky Island Medical Institute, LLC
Saint Petersburg, , Russia
Federal Centre of Heart, Blood and Endocrinology named after V.A. Almazov
Saint Petersburg, , Russia
International Medical Center "SOGAZ", LLC
Saint Petersburg, , Russia
Saint-Petersburg City Pokrovskaya Hospital
Saint Petersburg, , Russia
Center "Diabetes", LLC
Samara, , Russia
Smolensk State Medical Academy, Sanatorium-Preventorium
Smolensk, , Russia
Tyumen State Medical Academy
Tyumen, , Russia
Voronezh Regional Clinical Hospital #1
Voronezh, , Russia
City Hospital named after N.A.Semashko
Yaroslavl, , Russia
Clinical Hospital for Emergency Care named after N.V. Solovyov
Yaroslavl, , Russia
Medical Sanitary Unit of Novo-Yaroslavsky Oil Refinery
Yaroslavl, , Russia
Yaroslavl Regional Clinical Hospital
Yaroslavl, , Russia
The Urals State Medical Academy
Yekaterinburg, , Russia
Clinical Center of Serbia
Belgrade, , Serbia
Zvezdara University Medical Center
Belgrade, , Serbia
Clinical Center of Kragujevac
Kragujevac, , Serbia
METABOLKLINIK s.r.o.
Bratislava, Bratislava Region, Slovakia
Metabolic Center of Dr. Katarina Raslova Ltd.
Bratislava, Bratislava Region, Slovakia
ARETEUS s.r.o., Diabetologicka ambulancia
Trebišov, Košice Region, Slovakia
MediVet s.r.o.
Malacky, , Slovakia
ENDIAMED s.r.o
Dolný Kubín, Žilina Region, Slovakia
Newkwa Medical Centre
Newlands West, Durban, South Africa
Drs. Naiker and Naicker Inc.
Overport, Durban, South Africa
Centre for Diabetes and Endocrinology Suite 1
Durban, , South Africa
Centre for Diabetes, Asthma and Allergy
Johannesburg, , South Africa
Soweto Clinical Trial Centre
Johannesburg, , South Africa
Centre fro Diabetes and Endocrinology (Pty) Ltd
Johannesburg, , South Africa
Aliwal Shoal Medical & Clinical Trial Centre
Kwa Zulu Natal, , South Africa
Paarl Research Centre
Paarl, Cape Town, , South Africa
Helderberg Clinical Trials Centre
Somerset West, , South Africa
Tiervlei Trial Centre
Western Cape, , South Africa
Chulalongkorn University
Patumwan, Bangkok, Thailand
Phramongkutklao Hospital
Bangkok, , Thailand
Rajavithi Hospital
Bangkok, , Thailand
Songklanagarind Hospital
Songkhla, , Thailand
City Clinical Hospital#9, Dnipropetrovsk State Medical Academy
Dnipropetrovsk, , Ukraine
Educational Scientific Medical Centre "University clinic" of Donetsk National Medical University n.a. M.Gorkiy
Donetsk, , Ukraine
Administration of Medical Service and Rehabilitation of "ARTEM" State Holding Company
Kyiv, , Ukraine
National Medical University n.a. O.O. Bogomolets, Chair of Family Medicine based on Outpatient Clinic # 2 of Shevchenkovsky District
Kyiv, , Ukraine
V. P. Komissarenko Institute of Endocrinology and Metabolism of AMS of Ukraine
Kyiv, , Ukraine
Municipal Institution Lutsk City Clinical Hospital
Lutsk, , Ukraine
Lviv Regional Endocrinology Dispensary
Lviv, , Ukraine
Odessa State Medical University
Odesa, , Ukraine
Zhytomyr Regional Clinical Hospital
Zhytomyr, , Ukraine
Countries
Review the countries where the study has at least one active or historical site.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
GS-US-259-0110
Identifier Type: -
Identifier Source: org_study_id