A Study of BMS-512148 (Dapagliflozin) in Patients With Type 2 Diabetes and Inadequately Controlled Hypertension on an Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker

Type 2 Diabetes Clinical Trial

Official title:

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Phase 3 Trial to Evaluate the Safety and Efficacy of Dapagliflozin in Subjects With Type 2 Diabetes With Inadequately Controlled Hypertension on an Angiotensin-Converting Enzyme Inhibitor (ACEI) or Angiotensin Receptor Blocker (ARB)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01137474
• Other study ID #: MB102-073 ST
• Secondary ID: 2010-019797-32
• Status: Completed
• Phase: Phase 3
• First received: June 3, 2010
• Last updated: April 1, 2014
• Start date: July 2010
• Est. completion date: February 2013

Study information

• Verified date: April 2014
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug AdministrationCanada: Health CanadaMexico: Secretaria de SaludGermany: Federal Institute for Drugs and Medical DevicesAustralia: Department of Health and Ageing Therapeutic Goods AdministrationColombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y AlimentosHungary: National Institute of PharmacyPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsRussia: Ministry of Health of the Russian Federation
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to learn whether dapagliflozin, after 12 weeks, can improve (decrease) blood pressure in patients with type 2 diabetes with uncontrolled hypertension who are on an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. The safety of this treatment will also be studied.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2996
• Est. completion date: February 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 89 Years

Eligibility

Key inclusion criteria

• Participants willing and able to give signed and written informed consent

• Males and females, aged 18 to 89 years, who have type 2 diabetes with inadequate glycemic control (hemoglobin A1c between 7% and 10.5%) and uncontrolled hypertension (systolic blood pressure of 140 to 165 mm Hg and diastolic blood pressure 85 to 105 mm Hg)

• Stable dose of oral antidiabetic agent (OAD) for at least 6 weeks (12 weeks for thiazolidinedione) or a stable daily dose of insulin as monotherapy or in combination with another OAD, for 8 weeks, and a stable dose of an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker for at least 4 weeks

• C-peptide level =0.8 ng/mL

• Body mass index 45.0 kg/m^2

Key exclusion criteria

• Aspartate aminotransferase or alanine aminotransferase level >3*upper limit of normal (ULN)

• Serum total bilirubin level >1.5*ULN

• Serum creatinine =2.0 mg/dL unless subject was on metformin, where exclusionary limits were serum creatinine =1.50 mg/dL for women and =1.40 mg/dL for men

• Serum creatinine level <1.50 mg/dL for men or <1.40 mg/dL for women

• Estimated creatinine clearance of <60 mL/min

• Hemoglobin =10.0 g/dL for men and =9.0 g/dL for women

• Creatine kinase >3*ULN

• Positive for hepatitis B surface antigen

• Positive for antihepatitis C virus antibody

• Abnormal free T4 value

• History of diabetes insipidus

• Symptoms of poorly controlled diabetes that would preclude participation in this trial, including but not limited to, marked polyuria and polydipsia with greater than 10% weight loss during the 3 months prior to enrollment.

• History of diabetic ketoacidosis or hyperosmolar nonketotic coma

• History of malignant and accelerated hypertension

• Known or suspected secondary hypertension

• Any of the following within 6 months of enrollment visit:

• Myocardial infarction

• Cardiac surgery or revascularization (coronary artery bypass surgery /percutaneous transluminal coronary angioplasty)

• Unstable angina

• Unstable congestive heart disease New York Heart Association Class III or IV

• Transient ischemic attack or significant cerebrovascular disease

• Unstable or previously undiagnosed arrhythmia

Study Design

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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• Dapagliflozin
Oral tablets administered as 2.5, 5, or 10 mg, once daily for up to 12 weeks
• Placebo-matching dapagliflozin
Oral tablets administered as 0 mg once daily for up to 12 weeks
• Oral antidiabetic agent

• Angiotensin-converting enzyme (ACE) inhibitor or angiotensin-receptor blocker (ARB)
Patients were previously taking an ACE inhibitor or ARB
• With or without insulin
Patients may or may not have been taking insulin

Locations

Country	Name	City	State
Canada	Local Institution	Brampton	Ontario
Canada	Local Institution	Granby	Quebec
Canada	Local Institution	Kelowona	British Columbia
Canada	Local Institution	Montreal	Quebec
Canada	Local Institution	Saskatoon	Saskatchewan
Canada	Local Institution	Victoria	British Columbia
Colombia	Local Institution	Armenia	Quindio
Colombia	Local Institution	Barranquilla
Colombia	Local Institution	Barranquilla
Colombia	Local Institution	Bogota
Colombia	Local Institution	Bogota	Cundinamarca
Colombia	Local Institution	Cali	Valle
Colombia	Local Institution	Medellin	Antioquia
Czech Republic	Local Institution	Beroun
Czech Republic	Local Institution	Cheb
Czech Republic	Local Institution	Havirov
Czech Republic	Local Institution	Liberec
Czech Republic	Local Institution	Ostrava
Czech Republic	Local Institution	Prague 1
Czech Republic	Local Institution	Praha 4
Denmark	Local Institution	Copenhagen
Denmark	Local Institution	Copenhagen
Denmark	Local Institution	Frederiksberg
Denmark	Local Institution	Slagelse
Finland	Local Institution	Kokkola
Finland	Local Institution	Oulu
Germany	Local Institution	Aschaffenburg	Bavaria
Germany	Local Institution	Bad Kreuznach
Germany	Local Institution	Berlin
Germany	Local Institution	Duisburg	Nordrhein-Westfalen
Germany	Local Institution	Karlsruhe
Germany	Local Institution	Kothen
Germany	Local Institution	Kronshagen
Germany	Local Institution	Langenfeld
Germany	Local Institution	Lueneburg
Germany	Local Institution	Magdeburg
Germany	Local Institution	Mainz
Germany	Local Institution	Mannheim
Germany	Local Institution	Pirna
Germany	Local Institution	Saarbruecken
Germany	Local Institution	Vellmar	Hessen
Hungary	Local Institution	Eger
Hungary	Local Institution	Gyongyos	Heves
Hungary	Local Institution	Hatvan
Hungary	Local Institution	Miskolc
Hungary	Local Institution	Nagykanizsa
Hungary	Local Institution	Nyiregyhaza
Hungary	Local Institution	Satoraljaujhely
Hungary	Local Institution	Sopron
Hungary	Local Institution	Szeged
Hungary	Local Institution	Szekszard
Hungary	Local Institution	Szentes
India	Local Institution	Bangalore	Karnataka
India	Local Institution	Bangalore	Karnataka
India	Local Institution	Bangalore
India	Local Institution	Belgaum	Karnatka
India	Local Institution	Coimbatore	Tamil Nadu
India	Local Institution	Delhi	New Delhi
India	Local Institution	Hyderabad
India	Local Institution	Hyderabad	Andhra Pradesh
India	Local Institution	Indore	Madhya Pradesh
India	Local Institution	Jaipur	Rajasthan
India	Local Institution	Jaipur	Rajasthan
India	Local Institution	Jaipur	Rajasthan
India	Local Institution	Madurai	Tamilnadu
India	Local Institution	Manipal
India	Local Institution	Nagpur
India	Local Institution	Nagpur	Maharashtra
India	Local Institution	Nagpur	Maharashtra
India	Local Institution	Nagpur	Maharashtra
India	Local Institution	New Delhi	Delhi
India	Local Institution	Vijayawada	Andhra Pradesh
Mexico	Local Institution	Chihuahua
Mexico	Local Institution	Cuautla	Morelos
Mexico	Local Institution	Culiacan	Sinaloa
Mexico	Local Institution	Del. Benito Juarez	Distrito Federal
Mexico	Local Institution	Durango
Mexico	Local Institution	Guadalajara
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Merida	Yucatan
Mexico	Local Institution	Mexico City	Distrito Federal
Mexico	Local Institution	Mexico, Df	Distrito Federal
Mexico	Local Institution	Monterrey	Nuevo Leon
Mexico	Local Institution	Puebla
Mexico	Local Institution	Queretaro
Mexico	Local Institution	Tlalpan	Distrito Federal
Mexico	Local Institution	Torreon	Coahuila
Mexico	Local Institution	Veracruz
Peru	Local Institution	Arequipa
Peru	Local Institution	Arequipa
Peru	Local Institution	Chiclayo	Lambayeque
Peru	Local Institution	Cusco
Peru	Local Institution	Ica
Peru	Local Institution	Lima
Peru	Local Institution	Lima
Peru	Local Institution	Lima
Peru	Local Institution	Lima
Peru	Local Institution	Lima
Peru	Local Institution	Lince	Lima
Peru	Local Institution	Piura
Poland	Local Institution	Bialystok
Poland	Local Institution	Bydgoszcz
Poland	Local Institution	Chrzanow
Poland	Local Institution	Gdansk
Poland	Local Institution	Gdynia
Poland	Local Institution	Golub-Dobrzyn
Poland	Local Institution	Kamieniec Zabkowicki
Poland	Local Institution	Katowice
Poland	Local Institution	Krakow
Poland	Local Institution	Krakow
Poland	Local Institution	Krakow
Poland	Local Institution	Lodz
Poland	Local Institution	Lodz
Poland	Local Institution	Lodz
Poland	Local Institution	Ostroda
Poland	Local Institution	Poznan
Poland	Local Institution	Szczecin
Poland	Local Institution	Warsaw
Poland	Local Institution	Warsaw
Poland	Local Institution	Warszawa
Poland	Local Institution	Warszawa
Poland	Local Institution	Warszawa
Poland	Local Institution	Warszawa
Poland	Local Institution	Wroc#Aw
Poland	Local Institution	WrocB Aw
Poland	Local Institution	Zamosc
Puerto Rico	Local Institution	Cidra
Puerto Rico	Local Institution	Ponce
Puerto Rico	Local Institution	Ponce
Puerto Rico	Local Institution	San Juan
Romania	Local Institution	Bucuresti
Romania	Local Institution	Bucuresti
Romania	Local Institution	Bucuresti
Romania	Local Institution	Bucuresti
Romania	Local Institution	Oradea	Bihor
Romania	Local Institution	Oradea	Jud. Bihor
Romania	Local Institution	Ploiesti	Prahova
Romania	Local Institution	Ploiesti	Prahova
Romania	Local Institution	Satu Mare
Romania	Local Institution	Sibiu
Romania	Local Institution	Sibiu
Romania	Local Institution	Targu Mures	Mures
Romania	Local Institution	Targu Mures	Mures
Romania	Local Institution	Timisoara	Timis
Romania	Local Institution	Timisoara	Jud. Timis
Russian Federation	Local Institution	Dzerzhinskiy
Russian Federation	Local Institution	Krasnoyarsk
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Novosibirsk
Russian Federation	Local Institution	Saint Petersburg
Russian Federation	Local Institution	Saratov
Russian Federation	Local Institution	Smolensk
Russian Federation	Local Institution	St. Petersburg
Russian Federation	Local Institution	St.Petersburg
Russian Federation	Local Institution	Yaroslav
Russian Federation	Local Institution	Yaroslavl
Russian Federation	Local Institution	Yaroslavl
Spain	Local Institution	Barcelona
Spain	Local Institution	La Roca Del Valles
Spain	Local Institution	Peralada
Spain	Local Institution	Santiago De Compostela	A Coruna
United States	Cmp Research	Anaheim	California
United States	Orange County Research Institute	Anaheim	California
United States	Southeastern Research Associates, Inc.	Anderson	South Carolina
United States	Arlington Family Research Center, Inc.	Arlington	Texas
United States	Millennium Clinical Trials Llc	Arlington	Virginia
United States	Perimeter Institute For Clinical Research	Atlanta	Georgia
United States	Aurora Family Medicine, P.C.	Aurora	Colorado
United States	American Health Network Of Indiana Llc	Avon	Indiana
United States	Bainbridge Medical Associates	Bainbridge	Georgia
United States	Acadia Clinical Research, Llc	Bangor	Maine
United States	Medical Development Centers, Llc	Baton Rouge	Louisiana
United States	The Center For Clinical Trials	Biloxi	Mississippi
United States	University Of Alabama At Birmingham	Birmingham	Alabama
United States	River Birch Research Alliance, Llc	Blue Ridge	Georgia
United States	Zasa Clinical Research	Boynton Beach	Florida
United States	Bradenton Research Center, Inc.	Bradenton	Florida
United States	Neurocare, Inc.	Brookline	Massachusetts
United States	Meridien Research	Brooksville	Florida
United States	Southeastern Pa Medical Institute	Broomall	Pennsylvania
United States	Investigators Research Group, Llc	Brownsburg	Indiana
United States	Burke Internal Medicine And Research	Burke	Virginia
United States	Community Health Care, Inc.	Canal Fulton	Ohio
United States	Med Center	Carmichael	California
United States	Barat Research Group, Inc.	Charlotte	North Carolina
United States	Chattanooga Research & Medicine, Pllc	Chattanooga	Tennessee
United States	Cedar Crosse Research Center	Chicago	Illinois
United States	James R. Herron, Md, Ltd	Chicago	Illinois
United States	Catalina Research Institute, Llc	Chino	California
United States	Family Care Associates Of Nw Fl	Chipley	Florida
United States	Community Research	Cincinnati	Ohio
United States	Innovative Research Of West Florida, Inc	Clearwater	Florida
United States	Clinical Research Of South Florida	Coral Gables	Florida
United States	Internal Medicine Clinical Research	Dallas	Texas
United States	Krk Medical Research	Dallas	Texas
United States	Renaissance Clinical Research And Hypertension Pllc	Dallas	Texas
United States	Research Institute Of Dallas	Dallas	Texas
United States	Avail Clinical Research, Llc	Deland	Florida
United States	Horizons Clinical Research Center, Llc	Denver	Colorado
United States	In Vivo Clinical Research	Doral	Florida
United States	In-Quest Medical Research, Llc	Duluth	Georgia
United States	Sergio F. Rovner, M.D.	El Paso	Texas
United States	Central Jersey Medical Research Center	Elizabeth	New Jersey
United States	Willamette Valley Clinical Studies	Eugene	Oregon
United States	Genesis Clinical Research, Llc	Fall River	Massachusetts
United States	Lillestol Research	Fargo	North Dakota
United States	Abington Memorial Hos/Feasterville Family Health Care Center	Feasterville Trevose	Pennsylvania
United States	Southland Clinical Research Center, Inc.	Fountain Valley	California
United States	American Health Network Of In Llc	Franklin	Indiana
United States	Marin Endocrine Care & Research, Inc.	Greenbrae	California
United States	Pharmquest	Greensboro	North Carolina
United States	Southeastern Research Associates, Inc.	Greenville	South Carolina
United States	Clin Research Advantage, Inc. James Meli, Do Family Pracice	Henderson	Nevada
United States	Palm Springs Research Institute	Hialeah	Florida
United States	The Community Research Of South Florida	Hialeah	Florida
United States	Excel Clinical Research, Llc	Houston	Texas
United States	Lone Star Clinical Research	Houston	Texas
United States	Mercury Clinical Research	Houston	Texas
United States	Southwest Clinical Trials	Houston	Texas
United States	Del Rosario Medical Clinic, Inc.	Huntington Park	California
United States	Time Clinical Research Inc.	Huntington Park	California
United States	Phillips Medical Services, Pllc	Jackson	Mississippi
United States	Jefferson City Medical Group	Jefferson City	Missouri
United States	The Clinical Trial Center, Llc	Jenkintown	Pennsylvania
United States	Kcumb Dybedal Clinical Research Center	Kansas City	Montana
United States	Complete Family Care Of Knoxville, Pllc	Knoxville	Tennessee
United States	Clinical Research Advantage, Inc.	Las Vegas	Nevada
United States	Independent Clinical Researchers@ Wolfson Medical Center	Las Vegas	Nevada
United States	Office Of Ted Thorp, Md	Las Vegas	Nevada
United States	Palm Medical Research Center	Las Vegas	Nevada
United States	Aureus Research, Inc.	Little Rock	Arkansas
United States	Preferred Research Partners, Inc.	Little Rock	Arkansas
United States	Marina Raikhel, M.D., F.A.A.F.P	Lomita	California
United States	American Institute Of Research	Los Angeles	California
United States	Clinica Medica San Miguel	Los Angeles	California
United States	National Research Inst	Los Angeles	California
United States	Quest Diagnostics West Hills	Los Angeles	California
United States	Randall G. Shue, D.O.	Los Angeles	California
United States	Exodus Healthcare Network	Magna	Utah
United States	Manassas Clinical Research Center	Manassas	Virginia
United States	Premier Internal Medicine	Memphis	Tennessee
United States	Crescent City Clinical Research Center	Metairie	Louisiana
United States	Apf Research, Llc	Miami	Florida
United States	Baptist Diabetes Associates, Pa	Miami	Florida
United States	Clinical Research Of Miami, Inc.	Miami	Florida
United States	Community Research Foundation, Inc.	Miami	Florida
United States	Flcri Global Research, Llc	Miami	Florida
United States	International Research Associates, Llc	Miami	Florida
United States	Medical Research Marseilles	Miami	Florida
United States	San Marcus Research Clinic, Inc.	Miami	Florida
United States	Newphase Clinical Trials, Inc.	Miami Beach	Florida
United States	Ocean Blue Medical Research Center, Inc.	Miami Springs	Florida
United States	Laporte County Institute For Clinical Research, Inc.	Michigan City	Indiana
United States	Cleveland Sleep Research Center	Middleburg Heights	Ohio
United States	Horizon Research Group, Inc.	Mobile	Alabama
United States	Burke Primary Care	Morganton	North Carolina
United States	American Health Network Of In Llc	Muncie	Indiana
United States	Joslin Diabetes Center Affiliate Of Snhmc	Nashua	New Hampshire
United States	Hci-Metromedic Walk-In Medical Office	New Bedford	Massachusetts
United States	Hill Country Medical Associates	New Braunfels	Texas
United States	Suncoast Clinical Research, Inc.	New Port Richey	Florida
United States	Medex Healthcare Research, Inc.	New York	New York
United States	Digiovanna Institute For Medical Education & Research	North Massapequa	New York
United States	North Hills Medical Research, Inc.	North Richland Hills	Texas
United States	Diabetes Medical Center Of California	Northridge	California
United States	Valley Clinical Trials	Northridge	California
United States	Lucita M. Cruz,Md.,Inc.	Norwalk	California
United States	Providence Park Clinical Research	Novi	Michigan
United States	So. Illinois Clin Res Ctr @ Div Of Kevin L Pritchett Md, Pc	O?Fallon	Illinois
United States	Integris Family Care Central	Oklahoma City	Oklahoma
United States	Sooner Clinical Research	Oklahoma City	Oklahoma
United States	Sds Clinical Trials	Orange	California
United States	Compass Research, Llc	Orlando	Florida
United States	Florida Institute For Clinical Research, Llc	Orlando	Florida
United States	Iicr, Inc. (International Institute Of Clinical Research)	Ozark	Alabama
United States	Med-Olam Clinical Research	Pasadena	Texas
United States	Middle Georgia Clinical Research Center, Llc	Perry	Georgia
United States	Clinical Research Source, Inc	Perrysburg	Ohio
United States	Arcuri Clinical Research Llc	Philadelphia	Pennsylvania
United States	Philadelphia Health Associates - Adult Medicine	Philadelphia	Pennsylvania
United States	43rd Medical Associates	Phoenix	Arizona
United States	Hope Research Institute	Phoenix	Arizona
United States	Banksville Medical Pc	Pittsburgh	Pennsylvania
United States	Lisa E. Medwedeff, Md, Pa	Plano	Texas
United States	Sound Medical Research	Port Orchard	Washington
United States	Fanno Creek Clinic	Portland	Oregon
United States	Research Across America	Reading	Pennsylvania
United States	Integrated Research Group, Inc.	Riverside	California
United States	Jackson Clinic	Rolling Fork	Mississippi
United States	Endocrine Research Solutions, Inc.	Roswell	Georgia
United States	Quality Control Research, Inc	Sacramento	California
United States	Wasatch Clinical Research	Salt Lake City	Utah
United States	Wasatch Endocrinology And Diabetes Specialists	Salt Lake City	Utah
United States	Abbott Clinical Research Group, Inc.	San Antonio	Texas
United States	Covenant Clinical Research, Pa	San Antonio	Texas
United States	Sun Research Institute	San Antonio	Texas
United States	Crest Clinical Trials, Inc.	Santa Ana	California
United States	Orrin M. Troum, Md And Medical Associates	Santa Monica	California
United States	Alternative Primary Care	Silver Spring	Maryland
United States	Hillcrest Clinical Reseach, Llc	Simpsonville	South Carolina
United States	South Miami Clinical Research, Llc	South Miami	Florida
United States	Springfield Diabetes And Endocrine Center	Springfield	Illinois
United States	Meridien Research	St Petersburg	Florida
United States	St. Louis Center For Clinical Research	St. Louis	Missouri
United States	Hampton Roads Center For Clinical Research, Inc.	Suffolk	Virginia
United States	Breco Research, Ltd	Sugarland	Texas
United States	Pioneer Research Solutions, Inc.	Sugarland	Texas
United States	Palmetto Clinical Research	Summerville	South Carolina
United States	Meridien Research	Tampa	Florida
United States	Central Phoenix Medical Clinic, Llc	Tempe	Arizona
United States	Clinical Research Advantage/Desert Clinical Research	Tempe	Arizona
United States	Premier Research	Trenton	New Jersey
United States	Eclipse Clinical Research	Tucson	Arizona
United States	Visions Clinical Research - Tucson	Tucson	Arizona
United States	Orange County Research Center	Tustin	California
United States	University Clinical Investigators, Inc.	Tustin	California
United States	Pish Medical Associates	Uniontown	Pennsylvania
United States	Tidewater Integrated Medical Research	Virginia Beach	Virginia
United States	Greater Providence Clinical Research, Llc	Warwick	Rhode Island
United States	Chase Medical Research, Llc	Waterbury	Connecticut
United States	Atlantic Clinical Trials, Llc	Watertown	Massachusetts
United States	Infosphere Clinical Research, Inc.	West Hills	California
United States	Southgate Medical Group	West Seneca	New York
United States	Pmg Research Of Wilmington Llc	Wilmington	North Carolina
United States	Integris Family Care Yukon	Yukon	Oklahoma

Sponsors (2)

Lead Sponsor	Collaborator
Bristol-Myers Squibb	AstraZeneca

Countries where clinical trial is conducted

United States,  Canada,  Colombia,  Czech Republic,  Denmark,  Finland,  Germany,  Hungary,  India,  Mexico,  Peru,  Poland,  Puerto Rico,  Romania,  Russian Federation,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With Adverse Events (AEs), Hypoglycemic Events, Related AEs, Death as Outcome, Serious Adverse Events (SAEs), Related SAEs, Discontinuations Due to SAEs, Discontinuations Due to AEs, and Discontinuations Due to Hypoglycemic Events	AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related=having certain, probable, possible, or unknown relationship to study drug. Includes nonserious AEs with onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment plus 4 days and SAEs with onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment plus 30 days. Includes data after rescue. Only hypoglycemia reported as an SAE is included in AE/SAE categories. All reported hypoglycemia events within 4 days of last day of treatment are included as hypoglycemic events.	Day 1 of treatment to last dose plus 4 days for AEs and hypoglycemic events and plus 30 days for SAEs	Yes
Other	Number of Participants With Clinical Laboratory Results Meeting Criteria for Marked Abnormality	Laboratory abnormalities were evaluated based on laboratory values meeting predefined marked abnormality (MA) criteria. Includes data after the start date of double-blind treatment up to and including the last day of double-blind treatment plus 4 days. BUN=blood urea nitrogen; preRX=pretreatment; unspecif=unspecified; ULN=upper limit of normal. High total calcium= =1 mg/dL from ULN and =0.5 mg/dL from preRX value; high inorganic phosphorus= =5.6 mg/dL if age 17-65 years or =5.1 mg/dL if age =66 years.	Day 1 of treatment to last dose, plus 4 days	Yes
Other	Changes From Baseline in Electrocardiogram (ECG) Findings at Week 12	The normality or abnormality of the ECG tracing, determined by the investigator, was summarized by normal or abnormal ECG tracing at Week 12 overall and at baseline. When the data at Week 12 were not available, the last observation before discontinuation of that patient was used for summary.	From Baseline to Week 12	Yes
Other	Changes From Baseline in Supine and Standing Systolic and Diastolic Blood Pressure (BP) at Week 12	Supine BP was measured prior to standing BP. The patient was to rest in the supine position for at least 5 minutes prior to measurement of BP. Supine BP was determined from 3 replicate measurements obtained at least 1 minute apart. The average BP was determined from these 3 replicate measurements. The patient then stood for 2 to 3 minutes. After this time, BP was measured with the arm supported at the antecubital fossa at heart level.	From Baseline to Week 12	Yes
Other	Changes From Baseline in Supine and Standing Heart Rate (HR) at Week 12	Supine HR was measured prior to the standing HR. The patient was to rest in the supine position for at least 5 minutes prior to measurement of HR. Supine HR will be determined from 3 replicate measurements obtained at least 1 minute apart. The average HR was determined from these 3 replicate measurements and reported in the case report form. The patient then stood for 2 to 3 minutes. All measurements were to occur at least 10 hours after the last ingestion of caffeine, alcohol, or nicotine.	From Baseline to Week 12	Yes
Other	Changes From Baseline in 24-Hour Ambulatory Heart Rate at Week 12	Changes from baseline in 24-hour mean ambulatory heart rate were summarized at each visit using descriptive statistics.	From Baseline to Week 12	Yes
Other	Number of Participants With Elevated Results of Liver Laboratory Tests	ALT=alanine aminotransferase; ALP=alkaline phosphatase	Day 1 of double-blind treatment to last double-blind dose, plus 30 days	Yes
Primary	Adjusted Mean Change From Baseline in Seated Systolic Blood Pressure (BP) at Week 12	Seated BP was to be measured at every visit. Data after rescue medication was excluded. The patient first rested for at least 10 minutes in the seated position. Seated blood BP was determined from the mean of 3 replicated measurements obtained at least 1 minute apart. However, if the 3 consecutive seated BP readings were not within 8 mm Hg of each other, an additional 2 BP readings were to be obtained (total=5) and incorporated into the calculated mean for systolic BP and diastolic BP. For the initial BP recording, BP was measured in both arms. If the BP was higher in 1 arm, that arm was used for BP measurement. If there was no difference in BP measurements between arms, the dominant arm was used for all future BP measurements. All randomized participants who received at least 1 dose of study drug and who had nonmissing baseline and at least 1 postbaseline value during the double-blind treatment period were used for analysis. SD=standard deviation.	From Baseline to Week 12	No
Primary	Adjusted Mean Change From Baseline in Hemoglobin (HbA1c) at Week 12	HbA1c was measured as percent of hemoglobin by a central laboratory. All randomized participants who received at least 1 dose of study drug and who had nonmissing baseline and at least 1 postbaseline value during the double-blind treatment period were used for analysis. SD=standard deviation.	From Baseline to Week 12	No
Secondary	Adjusted Mean Change From Baseline in 24-Hour Ambulatory Systolic Blood Pressure at Week 12 (Last Observation Carried Forward)	Ambulatory blood pressure monitoring was performed twice during the study, at baseline and at the end of study, for a duration of 24-hrs each time. If the patient met the criteria for rescue due to hypertension, a second monitoring was performed prior to the first dose of rescue medication. Initiation of the 24-hr ambulatory blood pressure monitoring began between 6 and 11 am to ensure trough blood pressure measurements were obtained. Patients were instructed to withhold all medication on the morning of the study visit and to bring their medications to the visit with them.	From Baseline to Week 12	No
Secondary	Adjusted Mean Change From Baseline in Seated Diastolic Blood Pressure at Week 12	All randomized participants who received at least 1 dose of study drug and who had nonmissing baseline and at least 1 postbaseline value during the double-blind treatment period were used for analysis.	From Baseline to Week 12	No
Secondary	Adjusted Mean Change in 24-Hour Ambulatory Diastolic Blood Pressure at Week 12 (Last Observation Carried Forward [LOCF])	Ambulatory blood pressure monitoring was performed twice during the study, at baseline and at the end of study, for a duration of 24 hours each time. If the patient met the criteria for rescue due to hypertension, a second monitoring was performed prior to the first dose of rescue medication. Initiation of the 24-hour ambulatory blood pressure monitoring began between 6 and 11 am to ensure trough blood pressure measurements were obtained. Patients were instructed to withhold all medication on the morning of the study visit and to bring their medications to the visit with them.	From Baseline to Week 12	No
Secondary	Adjusted Mean Change From Baseline in Serum Uric Acid Levels at Week 12	Central laboratory serum uric acid levels will be determined at the Enrollment, Day -28, Day 1, and at Week 4, 8, 12, and 13 visits. All randomized participants who received at least 1 dose of study drug and who had nonmissing baseline and at least 1 postbaseline value during the double-blind treatment period were used for analysis.	From Baseline to Week 12	No

External Links

•   BMS clinical trial educational resource
•   BMS Clinical Trial Information
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
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