Ranolazine Monotherapy in Subjects With Type 2 Diabetes Mellitus

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 Monotherapy in Subjects With Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01472185
• Other study ID #: GS-US-259-0131
• Status: Completed
• Phase: Phase 3
• First received: November 11, 2011
• Last updated: October 15, 2014
• Start date: November 2011
• Est. completion date: October 2013

Study information

• Verified date: October 2014
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review BoardCzech Republic: Ethics CommitteeCzech Republic: State Institute for Drug ControlHungary: Institutional Ethics CommitteeHungary: National Institute of PharmacyPoland: Ethics CommitteePoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsRomania: Ethics CommitteeRomania: National Medicines AgencyRussia: Ethics CommitteeRussia: Ministry of Health of the Russian FederationSerbia and Montenegro: Agency for Drugs and Medicinal DevicesSerbia: Ethics CommitteeSlovakia: State Institute for Drug ControlSlovakia: Ethics CommitteeSouth Africa: Human Research Ethics CommitteeSouth Africa: Medicines Control CouncilUkraine: Ethics CommitteeUkraine: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

This is a randomized, double-blind, placebo-controlled, parallel-group, multi-center study to determine the effect of ranolazine when given as monotherapy on glycemic control in subjects with type 2 diabetes mellitus (T2DM) who were inadequately controlled with diet and exercise alone and who are treatment naive to antihyperglycemic therapy or have not received antihyperglycemic therapy in the 90 days (or thiazolidinediones [TZDs] for at least 24 weeks) prior to screening, and to characterize the relationship between HbA1c reduction and other glycemic parameters in subjects with T2DM.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 465
• Est. completion date: October 2013
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Written informed consent

• Males and females, 18 to 75 years old, inclusive

• Documented history of T2DM

• Treatment naïve to antihyperglycemic therapy or having received no prior treatment with antihyperglycemic therapy for at least 90 days (TZDs for at least 24 weeks) prior to screening

• Body mass index (BMI) 25 kg/m2 to 45 kg/m2 inclusive at screening

• HbA1c 7% - 10%, inclusive at screening and at the end of the Qualifying Period (Day 14 +2 days)

• Fasting serum glucose (FSG) of = 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 +2 days). A one-time central laboratory re-test of FSG is allowed in subjects with an initial central laboratory FSG = 125 mg/dL (6.9 mmol/L) and < 130 mg/dL (7.2 mmol/L) who are otherwise eligible as determined by the investigator.

• Fasting serum C-peptide = 0.8 ng/mL at screening

• Able and willing to comply with all study procedures during the course of the study

• Females of child-bearing potential must have a negative 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 with dosing during the Qualifying Period

Exclusion Criteria:

• History of or current diagnosis of type 1 diabetes mellitus

• 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 or cerebrovascular event (eg, myocardial infarction [MI], acute coronary syndrome [ACS], recent coronary 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 systolic blood pressure (SBP) > 160 mmHg or diastolic blood pressure (DBP) > 100 mmHg at screening and randomization

• Prolonged QTc interval > 500 msec by 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 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 on a weight-loss program and is not in the 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) > 3x upper limit of the normal range (ULN) and/or alanine aminotransferase (ALT) > 3x ULN and/or serum total bilirubin > 2.0 mg/dL

• History of cancer (except non-melanomic 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

• Prior treatment with open-label ranolazine or known hypersensitivity or intolerance to ranolazine or any of its excipients

• Treatment with strong or moderate cytochrome (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, sirolimus) within 14 days prior to randomization

• Treatment with simvastatin at a daily dose > 20 mg or lovastatin at a daily dose > 40 mg, within 14 days prior to randomization

• Weight-loss medication or anti-obesity medication (prescription or nonprescription) < 3 months prior to screening

• Treatment with niacin > 200 mg daily; if receiving = 200 mg daily, should be on stable doses for = 90 days prior to screening and for the duration of the study

• 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 antihyperglycemic therapy < 90 days prior to screening

• Donation of blood < 2 months prior to screening; plans to donate blood while participating in the study

• Females who are pregnant or breastfeeding

• Other condition(s) that, in the opinion of the investigator, would compromise the safety of the subject, would prevent compliance with the study protocol (including the ability to comply with Mixed Meal Tolerance Test [MMTT]), or would compromise the quality of the clinical study

Study Design

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Ranolazine
Ranolazine tablets administered orally twice daily.
• Placebo
Placebo to match ranolazine administered orally twice daily.

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
Czech Republic	Nemocnice s poliklinikou Havirov	Havirov	Moravskoslezsky kraj
Hungary	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	Zala County Hospital	Zalaegerszeg
Poland	NZOZ Centrum Osteporozy i Chorob Kostno-Stawowych J.Badurski Sp.j.	Bialystok
Poland	Leszek Romanowski Barbara Romanowska "DIABET" Centrum Medyczne s.c.	Chrzanów
Poland	NZOZ PrimaMED	Kielce	Swietokrzyskie
Poland	LANDA - Specjalistyczne Gabinety Lekarskie	Krakow	Malopolskie
Poland	NZOZ Specjalistyczna Przychodnia Medyczna Atopia	Krakow
Poland	NZOZ Centrum Medyczne Szpital Sw. Rodziny	Lodz	Lodzkie
Poland	NZOZ Cereo-Med Sp. z o.o.	Lodz
Poland	SPZOZ Uniwersytecki Szpital Kliniczny Nr 1 im. Norberta Barlickiego Uniwersytetu Medycznego w Lodzi, Oddzial Kliniczny Diabetologii	Lodz	Lodzkie
Poland	Specjalistyzny Osrodek Lecznicz-Badawczy	Ostroda
Poland	NZOZ Centrum Badan Klinicznych Oswiecim	Oswiecim	Malopolskie
Poland	Miedzyleski Szpital Specjalistyczny w Warszawie	Warszawa
Poland	NZOZ Centrum Badan Klinicznych	Wroclaw	Dolnoslaskie
Poland	NZOZ Regionalna Poradnia Diabetologiczna	Wroclaw	Dolnoslaskie
Poland	NZOZ Polimedica	Zgierz	Lodzkie
Romania	CMI Diabet Nutritie Boli Metabolice Dr. Pop Lavinia	Baia Mare	Jud. Maramures
Romania	Vitadiab SRL - Cabinet Medical Dr. Barabas Alina SRL	Brasov	Jud Brasov
Romania	Tehnomed Trading Srl	Bucharest
Romania	Institutul de Diabet, Nutritie si Boli Metabolice "Dr. N. C. Paulescu"	Bucuresti
Romania	O.D. Medica Srl	Bucuresti
Romania	CMI Morosanu V. Magdalena	Galati	Judetul Galati
Romania	Spitalul Clinic Judetean de Urgenta "Sf. Apostol Andrei" Galati	Galati	Judetul Galati
Romania	Consultmed SRL	Iasi	Jud. Iasi
Romania	Spital Clinic Judetean de Urgenta Oradea Stationarul 1	Oradea	Jud Bihor
Romania	Diabmed Dr. Popescu Alexandrina SRL	Ploiesti	Judetul Prahova
Romania	Centru Medical Dr. Negrisanu	Timisoara, jud. Timis
Russian Federation	3rd Central Military Clinical Hospital named after A.A.Vishnevskogo	Arkhangelskoe
Russian Federation	GOU VPO "Chita State Medical Academy" of Minzdravsocrazvitie RF	Chita
Russian Federation	"Clinic of New Medical Technology" Company Limited	Dzerzhinskiy
Russian Federation	The Urals State Medical Academy	Ekaterinburg
Russian Federation	Kemerovo Regional Clinical Hospital	Kemerovo
Russian Federation	"Krasnoyarsk State Medical University n.a. Prof. V.F. Voyno-Yasenetsky	Krasnoyarsk
Russian Federation	Central Clinical Hospital of Russian Academy of Sciences	Moscow
Russian Federation	Medical Sanitary Unit of Minestry of Internal Affairs of Russia in Moscow	Moscow
Russian Federation	Moscow City Clinical Hospital #63	Moscow
Russian Federation	State Healthcare Institution of Moscow "Cardiologival Dispensary #2 of Management Department of South Administrative District"	Moscow
Russian Federation	City Clinical Hospital # 13 of Avtozavodsky District of Nizhniy Novgorod	Nizhniy Novgorod
Russian Federation	LLC "Reafan"	Novosibirsk
Russian Federation	Novosibirsk State Medical University	Novosibirsk
Russian Federation	Scientific Research Institute of Physiology of Siberian Department RAMS	Novosibirsk
Russian Federation	City Hospital # 38 named after N A Semashko	Pushkin
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	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	International Medical Center "SOGAZ", LLC	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	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	Saint-Petersburg City Pokrovskaya Hospital	St. Petersburg
Russian Federation	Saint-Petersburg state budgetary healthcare institution "City Polyclinic #109"	St. Petersburg
Russian Federation	St. Elizabeth City Hospital	St. Petersburg
Russian Federation	Tyumen State Medical Academy	Tyumen
Russian Federation	Voronezh Regional Clinical Hospital #1	Voronezh
Russian Federation	City Hospital named after N.A.Semashko	Yaroslavl
Russian Federation	Clinical Hospital for Emergency Care named after N.V. Solovyov	Yaroslavl
Russian Federation	Medical Sanitary Unit of Novo-Yaroslavsky Oil Refinery	Yaroslavl
Russian Federation	Yaroslavl Regional Clinical Hospital	Yaroslavl
Serbia	Clinical Center of Serbia	Belgrade
Serbia	Clinical Center of Kragujevac	Kragujevac
Slovakia	Metabolic Center of Dr. Katarina Raslova Ltd.	Bratislava	Bratislavsky kraj
Slovakia	METABOLKLINIK s.r.o.	Bratislava	Bratislavsky kraj
Slovakia	ENDIAMED s.r.o	Dolny Kubin	Zilinsky kraj
Slovakia	"Diabetologicka a metabolicka ambulancia Human-care s.r.o"	Kosice	Kosicky kraj
Slovakia	MediVet s.r.o.	Malacky
Slovakia	ARETEUS s.r.o., Diabetologicka ambulancia	Trebisov	Kosicky kraj
Slovakia	MEDIVASA s.r.o.	Zilina	Zilinsky kraj
South Africa	Worthwhile Clinical Trials	Benoni
South Africa	Centre for Diabetes, Asthma and Allergy	Johannesburg
South Africa	Soweto Clinical Trial Centre	Johannesburg
South Africa	Aliwal Shoal Medical & Clinical Trial Centre	Kwa Zulu Natal
South Africa	Netcare Umhlanga Medical Centre	Kwa Zulu Natal	Umhlanga, Durban
South Africa	Newkwa Medical Centre	Newlands West	Durban
South Africa	Global Clinical Trials	Pretoria
South Africa	Helderberg Clinical Trials Centre	Somerset West
South Africa	Tiervlei Trial Centre	Western Cape
Ukraine	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	State Institution "Institute of Problems of Endocrine Pathology n.a. V.Y. Danylevsky of NAMS of Ukraine"	Kharkiv
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	Public Institution "City Outpatients' Hospital #20"	Odesa
Ukraine	Vinnytsya Regional Clinical Endocrinology Dispensary	Vinnytsya
Ukraine	Zhytomyr Regional Clinical Hospital	Zhytomyr
United States	Albuquerque Clinical Trials	Albuquerque	New Mexico
United States	University of New Mexico Clinical and Translational Science Center	Albuquerque	New Mexico
United States	Blair Medical Associates, Inc, Station Medical Center	Altoona	Pennsylvania
United States	Synergy Therapeutic Partners	Atlanta	Georgia
United States	Associated Internal Medicine Specialists, P.C.	Battle Creek	Michigan
United States	Clinical Inquest Center, Ltd.	Beavercreek	Ohio
United States	Boca Raton Clinical Research Associates, Inc	Boca Raton	Florida
United States	PAB Clinical Research	Brandon	Florida
United States	Burke Internal Medicine & Research	Burke	Virginia
United States	PMG Research of Charlotte	Charlotte	North Carolina
United States	Cedar-Crosse Research Center	Chicago	Illinois
United States	HCCA Clinical Research Solutions	Columbia	Tennessee
United States	The University of Texas Southwestern Medical Center at Dallas	Dallas	Texas
United States	CTL Research	Eagle	Idaho
United States	Southland Clinical Research Center, Inc.	Fountain Valley	California
United States	Florida Research Network, LLC	Gainesville	Florida
United States	Global Research Management	Glendale	California
United States	Thunderbird Internal Medicine/Clinical Research Advantage	Glendale	Arizona
United States	PharmQuest	Greensboro	North Carolina
United States	A G A Clinical Trials	Hialeah	Florida
United States	Excel Clinical Research, LLC	Houston	Texas
United States	Texas Center for Drug Development, PA	Houston	Texas
United States	Humble Cardiology Associates	Humble	Texas
United States	HCCA Clinical Research Solution	Jackson	Tennessee
United States	Jacksonville Center for Clinical Research	Jacksonville	Florida
United States	Juno Research, LLC	Katy	Texas
United States	New Phase Research & Development	Knoxville	Tennessee
United States	National Research Institute	Los Angeles	California
United States	Manassas Clinical Research Center	Manassas	Virginia
United States	Clinical Trials Management, LLC	Metairie	Louisiana
United States	Baptist Diabetes Associates	Miami	Florida
United States	NextPhase Clinical Trials, Inc.	Miami Beach	Florida
United States	Precision Research Organization	Miami Lakes	Florida
United States	LaPorte County Institute for Clinical Research	Michigan City	Indiana
United States	Spectrum Clinical Research Institute, Inc	Moreno Valley	California
United States	North Central Arkansas Medical Associates	Mountain Home	Arkansas
United States	Suncoast Clinical Research	New Port Richey	Florida
United States	Clinical Research Solution	New York	New York
United States	Infinity Research Group, LLC	Oklahoma City	Oklahoma
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	Paul W. Davis, MD, Private Practice	Pine Bluff	Arkansas
United States	Sacramento Heart and Vascular Medical Associates	Sacramento	California
United States	PMG Research of Salisbury	Salisbury	North Carolina
United States	Highland Clinical Research	Salt Lake City	Utah
United States	Jean Brown Research	Salt Lake City	Utah
United States	Cetero Research	San Antonio	Texas
United States	Discovery Clinical Trials	San Antonio	Texas
United States	Clearview Medical Research LLC	Santa Clarita	California
United States	HCCA Clinical Research Solutions	Smyrrna	Tennessee
United States	Regenerate Clinical Trials	South Miami	Florida
United States	Southeastern Research Associates, Inc.	Taylors	South Carolina
United States	IRC Clinics, Inc	Towson	Maryland
United States	Desert Sun Clinical Research, LLC	Tucson	Arizona
United States	Eclipse Clinical Research	Tucson	Arizona
United States	Infosphere Clinical Research	West Hills	California

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Czech Republic,  Hungary,  Poland,  Romania,  Russian Federation,  Serbia,  Slovakia,  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	Percentage of Participants With HbA1c < 7% at Week 24		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 time [T] = 120 minutes during the MMTT, administered under fasting conditions, excluding participants with major eligibility protocol violations and analyzed based on the randomized treatment regardless of actual treatment received.	Baseline; Week 24	No
Secondary	Change From Baseline in Incremental Change of 2-hour Postprandial Serum Glucose at Week 24	The average (mean) change from baseline in incremental change of 2-hour postprandial serum glucose at Week 24 was analyzed.	Baseline; Week 24	No