A Study of BMS-512148 (Dapagliflozin) in Patients With Type 2 Diabetes With Inadequately Controlled Hypertension on an ACEI or ARB and an Additional Antihypertensive Medication

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 (ACE) Inhibitor or Angiotensin Receptor Blocker (ARB) and an Additional Antihypertensive Medication

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01195662
• Other study ID #: MB102-077 ST
• Secondary ID: 2010-019798-13
• Status: Completed
• Phase: Phase 3
• First received: September 3, 2010
• Last updated: December 2, 2015
• Start date: October 2010
• Est. completion date: February 2013

Study information

• Verified date: December 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationMexico: Secretaria de SaludAustralia: 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 FederationUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyDenmark: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to learn if BMS-512148 (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 (ACEI) or an Angiotensin Receptor Blocker (ARB).The safety of this treatment will also be studied

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2245
• 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

Inclusion Criteria:

• Written informed consent

• Males and females, 18 to 89 years old, with type 2 diabetes with inadequate glycemic control HbA1c between 7-10.5% and uncontrolled hypertension Systolic Blood Pressure (SBP) 140-165 and Diastolic Blood Pressure (DBP) 85-105

• Subjects must have a mean 24 hr blood pressure = 130/80 determined by Ambulatory Blood Pressure Monitoring (ABPM) within 1 week prior to Day 1 visit

• Stable dose of oral antidiabetic agent (OAD) for at least 6 weeks [12 wks for Thiazolidinedione (TZD)] or a stable daily dose of insulin, as a monotherapy or in combination with another OAD, for 8 weeks, and a stable dose of ACEI or ARB and 1 additional antihypertensive medication for at least 4 weeks

• C-peptide = 0.8 ng/mL

• Body Mass Index = 45.0 kg/m2

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

Exclusion Criteria:

• Aspartate aminotransferase (AST) and /or Alanine aminotransferase (ALT) > 3.0*upper limit of normal (ULN)

• Serum total bilirubin = 1.5*ULN

• Creatinine kinase > 3*ULN

• Symptoms of severely uncontrolled diabetes

• History of malignant or accelerated hypertension

• Currently unstable or serious cardiovascular, renal, hepatic, hematological, oncological, endocrine, psychiatric, or rheumatic diseases

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
• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• Dapagliflozin
Tablets, Oral, 10 mg, once daily, Up to 12 weeks
• Placebo matching Dapagliflozin
Tablets, Oral, 0 mg, once daily, Up to 12 weeks

Locations

Country	Name	City	State
Australia	Local Institution	Camperdown	New South Wales
Australia	Local Institution	Heidelberg	Victoria
Australia	Local Institution	Nedlands	Western Australia
Canada	Local Institution	Brampton	Ontario
Canada	Local Institution	Granby	Quebec
Canada	Local Institution	Kelowona	British Columbia
Canada	Local Institution	Monction	New Brunswick
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	Bucaramanga	Santander
Czech Republic	Local Institution	Beroun
Czech Republic	Local Institution	Cheb
Czech Republic	Local Institution	Havirov
Czech Republic	Local Institution	Krnov
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	Frederiksberg
Denmark	Local Institution	Gentofte
Denmark	Local Institution	Slagelse
Finland	Local Institution	Helsinki
Finland	Local Institution	Kerava
Finland	Local Institution	Kokkola
Finland	Local Institution	Oulu
Germany	Local Institution	Aschaffenburg	Bavaria
Germany	Local Institution	Augsburg	Bavaria
Germany	Local Institution	Bad Kreuznach
Germany	Local Institution	Berlin
Germany	Local Institution	Dortmund
Germany	Local Institution	Dresden
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	Saarbruecken
Germany	Local Institution	Wuestensachsen
Hungary	Local Institution	Budapest
Hungary	Local Institution	Budapest
Hungary	Local Institution	Eger
Hungary	Local Institution	Gyongyos	Heves
Hungary	Local Institution	Kisvarda
Hungary	Local Institution	Miskolc
Hungary	Local Institution	Nyiregyhaza
Hungary	Local Institution	Satoraljaujhely
Hungary	Local Institution	Sopron
Hungary	Local Institution	Szeged
Hungary	Local Institution	Szekszard
India	Local Institution	Bangalore	Karnataka
India	Local Institution	Bangalore	Karnataka
India	Local Institution	Bangalore	Karnataka
India	Local Institution	Belgaum	Karnatka
India	Local Institution	Chennai	Tamil Nadu
India	Local Institution	Chennai Tamilnadu
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	Madurai	Tamilnadu
India	Local Institution	Mangalore	Karnataka
India	Local Institution	Nagpur
India	Local Institution	Nagpur	Maharashtra
India	Local Institution	Nagpur	Maharashtra
India	Local Institution	Nagpur	Maharashtra
India	Local Institution	Trivandrum
Ireland	Local Institution	Dublin 15	Dublin
Ireland	Local Institution	Galway
Mexico	Local Institution	Chihuahua
Mexico	Local Institution	Cuautla	Morelos
Mexico	Local Institution	Culiacan	Sinaloa
Mexico	Local Institution	Del. Benito Juarez
Mexico	Local Institution	Delegacion Tlalpan
Mexico	Local Institution	Distrito Federal
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 City	Distrito Federal
Mexico	Local Institution	Monterrey	Nuevo Leon
Mexico	Local Institution	Monterrey	Nuevo Leon
Mexico	Local Institution	San Luis Potosi
Mexico	Local Institution	Torreon	Coahuila
Poland	Local Institution	Bialystok
Poland	Local Institution	Bialystok
Poland	Local Institution	Chrzanow
Poland	Local Institution	Elblag
Poland	Local Institution	Gdansk
Poland	Local Institution	Gdynia
Poland	Local Institution	Kamieniec Zabkowicki
Poland	Local Institution	Katowice
Poland	Local Institution	Kielce
Poland	Local Institution	Krakow
Poland	Local Institution	Krakow
Poland	Local Institution	Lodz
Poland	Local Institution	Lodz
Poland	Local Institution	Lublin
Poland	Local Institution	Ostroda
Poland	Local Institution	Poznan
Poland	Local Institution	Warsaw
Poland	Local Institution	Warsaw
Poland	Local Institution	Warszawa
Poland	Local Institution	Warszawa
Poland	Local Institution	Warszawa
Poland	Local Institution	Wroclaw
Poland	Local Institution	Wroclaw
Poland	Local Institution	Zabrze
Puerto Rico	Local Institution	Fajard
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	Cluj-Napoca
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
United Kingdom	Local Institution	Bath	Wiltshire
United Kingdom	Local Institution	Birmingham	West Midlands
United Kingdom	Local Institution	Ely	Cambridgeshire
United Kingdom	Local Institution	Irvine	Ayrshire
United States	Alexandria Health Care Center	Alexandria	Virginia
United States	Cmp Research	Anaheim	California
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	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	Comprehensive Clinical Research	Berlin	New Jersey
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	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	Medical Research South	Charleston	South Carolina
United States	Cedar Crosse Research Center	Chicago	Illinois
United States	Catalina Research Institute, Llc	Chino	California
United States	Community Research	Cincinnati	Ohio
United States	Innovative Research Of West Florida, Inc	Clearwater	Florida
United States	Parsons Avenue Medical Clinical	Columbus	Ohio
United States	Clinical Research Of South Florida	Coral Gables	Florida
United States	3rd Coast Research Associates	Corpus Christi	Texas
United States	Internal Medicine Clinical Reaseach	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	In-Quest Medical Research, Llc	Duluth	Georgia
United States	Sergio F. Rovner, M.D.	El Paso	Texas
United States	Willamette Valley Clinical Studies	Eugene	Oregon
United States	Lillestol Research	Fargo	North Dakota
United States	Abington Memorial Hos/Feasterville Family Health Care Center	Feasterville	Pennsylvania
United States	Larry D. Stonesifer, Md	Federal Way	Washington
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	Southeastern Research Associates, Inc.	Greenville	South Carolina
United States	Clin Research Advantage, Inc. James Meli, Do Family Pracice	Henderson	Nevada
United States	International Research Associates, Llc	Hialeah	Florida
United States	Palm Springs Research Institute	Hialeah	Florida
United States	The Community Research Of South Florida	Hialeah	Florida
United States	Bellaire Medical Care Group	Houston	Texas
United States	Dependable Clinical Research, Llc	Houston	Texas
United States	Excel Clinical Research, Llc	Houston	Texas
United States	Pioneer Research Solutions, Inc.	Houston	Texas
United States	Southwest Clinical Trials	Houston	Texas
United States	Village Family Practice	Houston	Texas
United States	Del Rosario Medical Clinic, Inc.	Huntington Park	California
United States	Time Clinical Research Inc.	Huntington Park	California
United States	Medical Affiliated Research Center, Inc.	Huntsville	Alabama
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	Missouri
United States	Clinical Investigation Specialists, Inc.	Kenosha	Wisconsin
United States	Central Florida Internists	Kissimmee	Florida
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	American Institute Of Research	Los Angeles	California
United States	Clinica Medica San Miguel	Los Angeles	California
United States	Mcs Clinical Trials	Los Angeles	California
United States	National Research Inst	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	Southwind Medical Specialists	Memphis	Tennessee
United States	Omega Clinical Research, Llc	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	Pharmax 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	Wilmax Clinical Research, Inc.	Mobile	Alabama
United States	Diabetes & Endocrinology Consultants	Morehead City	North Carolina
United States	Burke Primary Care	Morganton	North Carolina
United States	American Health Network Of In Llc	Muncie	Indiana
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	Christiana Care Health Services, Inc	Newark	Delaware
United States	Neurocare, Inc.	Newton	Massachusetts
United States	Digiovanna Institute For Medical Education & Research	North Massapequa	New York
United States	North Myrtle Beach Family Practice	North Myrtle Beach	South Carolina
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	Sooner Clinical Research	Oklahoma City	Oklahoma
United States	Sds Clinical Trials	Orange	California
United States	Florida Institute For Clinical Research, Llc	Orlando	Florida
United States	Bayview Research Group, Llc	Paramount	California
United States	Med-Olam Clinical Research	Pasadena	Texas
United States	Pawleys Pediatrics And Adult Medicine	Pawleys Island	South Carolina
United States	Michele A. Morrison Internal Medicine, Inc.	Pembroke Pines	Florida
United States	Middle Georgia Drug Study 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	Lisa E. Medwedeff, Md, Pa	Plano	Texas
United States	Medsol Clinical Research Center	Port Charlotte	Florida
United States	Sound Medical Research	Port Orchard	Washington
United States	San Diego Managed Care Group	Poway	California
United States	Research Across America	Reading	Pennsylvania
United States	Integrated Research Group, Inc.	Riverside	California
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	Innovative Clinical Trials	San Antonio	Texas
United States	Sun Research Institute	San Antonio	Texas
United States	Wetlin Research Associates, Inc.	San Diego	California
United States	Crest Clinical Trials, Inc.	Santa Ana	California
United States	Neurological Research Institute	Santa Monica	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	Tn Medical Research	Spring Hill	Tennessee
United States	Springfield Diabetes And Endocrine Center	Springfield	Illinois
United States	Hampton Roads Center For Clinical Research, Inc.	Suffolk	Virginia
United States	Breco Research, Ltd	Sugarland	Texas
United States	Palmetto Clinical Research	Summerville	South Carolina
United States	Meridien Research	Tampa	Florida
United States	Central Phoenix Medical Center	Tempe	Arizona
United States	Clinical Research Advantage, Inc./Mesa Family Med Ctr, Pc	Tempe	Arizona
United States	Clinical Research Advantage/Desert Clinical Research	Tempe	Arizona
United States	Torrance Clinical Research	Torrance	California
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	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	Southgate Medical Group	West Seneca	New York
United States	Integris Family Care Yukon	Yukon	Oklahoma

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Colombia,  Czech Republic,  Denmark,  Finland,  Germany,  Hungary,  India,  Ireland,  Mexico,  Poland,  Puerto Rico,  Romania,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adjusted Mean Change From Baseline in Seated Systolic Blood Pressure for 12 Week Double-Blind Treatment Period - Randomized Participants	Systolic blood pressure (SBP) was measured in millimeters of mercury (mmHg) on Day -1, Day 1, Weeks 2, 4, 8, and 12 of the Double Blind Period. Blood pressure (BP) values were obtained after the participant was seated for quietly for 10 minutes; a mean of 3 replicate measurements was taken 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 obtained (total = 5) and incorporated into the calculated mean. BP was measured in both arms. If the BP was higher in one arm than the other, then this arm was used; if no difference, the participant's dominant arm was used for all future BP measurements. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. Participants refrained from ingestion of caffeine, alcohol, or nicotine at least 10 hours prior to their visit and having their BP measured.	Baseline to Week 12	No
Primary	Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) for 12 Week Double-Blind Treatment Period - Randomized Participants	Adjusted mean change in glycosylated hemoglobin ( HbA1c) from baseline at Week 12 was calculated. HbA1c was measured as percent of hemoglobin by a central laboratory. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. HbA1c values were obtained at enrollment and lead-in (Day -28) periods, and at Day 1, Weeks 4, 8, and 12, in the double-blind period.	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 (LOCF)	Ambulatory 24 hour (hr) blood pressure monitoring (ABPM) was performed at baseline, which was during the lead-in period (between Day -7 and Day -1 prior to randomization) and 1 week prior to the Week 12 visit/end of treatment visit. If no Week 12 measurement was available, the last available earlier post-baseline measurement was used (LOCF) for analysis. Initiation of the 24-hr ABPM began between 6am and 11am to ensure trough BP measurements were obtained.The ABPM units were calibrated, and used per the manufacturer's and central ABPM vendor instructions. BP was measured in mmHg. Participants had to have a mean 24-hour ABPM = 130/80 mmHg prior to randomization. All medication was withheld on the morning of the study visit and brought to the visit site by the participant. Once the ABPM cuff was in place, all morning medication was taken while at the site.	Baseline, Week 12	No
Secondary	Adjusted Mean Change From Baseline in Seated Diastolic Blood Pressure (DBP) for 12 Week Double-Blind Treatment Period - Randomized Participants	Diastolic BP was measured in millimeters of mercury (mmHg) on Day -1, Day 1, Weeks 2, 4, 8, and 12 of the Double Blind Period. Diastolic BP values were obtained after the participant was seated for quietly for 10 minutes; a mean of 3 replicate measurements was taken 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 obtained (total = 5) and incorporated into the calculated mean. BP was measured in both arms. If the pressure was higher in one arm than the other, then this arm was used; if no difference, the participant's dominant arm was used for all future BP measurements. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. Participants refrained from ingestion of caffeine, alcohol, or nicotine at least 10 hours prior to their visit and having their BP measured.	Baseline to Week 12	No
Secondary	Adjusted Mean Change From Baseline in 24-hr Ambulatory Diastolic Blood Pressure at Week 12 (LOCF)	Ambulatory 24 hour (hr) BP monitoring (ABPM) was performed at baseline, which was during the lead-in period (between Day -7 and Day -1 prior to randomization) and 1 week prior to the Week 12 visit/end of treatment visit. If no Week 12 measurement was available, the last available earlier post-baseline measurement was used (LOCF). Initiation of the 24-hr ABPM began between 6am and 11am to ensure trough BP measurements were obtained. The ABPM units were calibrated, and used per the manufacturer's and central ABPM vendor instructions. BP was measured in mmHg. Participants had to have a mean 24-hour ABPM = 130/80 mmHg prior to randomization. All medication was withheld on the morning of the study visit and brought to the visit site by the participant. Once the ABPM cuff was in place, all morning medication was taken while at the site.	Baseline, Week 12	No
Secondary	Adjusted Mean Change From Baseline in Serum Uric Acid at Week 12 in Double-Blind Treatment Period - Randomized Participants	Adjusted mean change in serum uric acid from baseline at Week 12 was calculated. Serum uric acid was measured in milligrams per deciliter (mg/dL) by a central laboratory. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. Serum uric acid measurements were obtained at qualification and lead-in (Day -28) periods, and at Day 1, Weeks 4, 8, and 12, in the double-blind period but only the change from baseline at Week 12 was considered a secondary endpoint and is presented.	Baseline, Week 12	No
Secondary	Number of Participants With Deaths,Serious Adverse Events (SAEs), Adverse Events (AEs), Hypoglycemia Events, Discontinuation Due to AEs, SAEs and Hypoglycemia, During the 12 Week Double Blind Period, Including Data After Rescue	Medical Dictionary for Regulatory Activities (MedDRA), version 15.1 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 missing relationship to study drug as per the investigator. Events captured from baseline to last double blind dose plus 4 days for AEs, plus 30 days for SAEs during the Double Blind 12 Week Period. 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.	Baseline to last dose of 12 weeks of double blind medication plus 30 days if SAE or plus 4 days if AE/hypoglycemic event	Yes
Secondary	Number of Participants With Marked Chemistry Laboratory Abnormalities in 12 Week Double Blind Treatment Period, Including Data After Rescue	Samples obtained: Day 1, Weeks 4, 8,12 in Double Blind Period. Baseline: last assessment prior to start of first dose of double-blind treatment. Pretreatment (PreRX); grams per deciliter (g/dL); upper limit of normal (ULN); milliequivalent per liter (mEq/L); greater than (>) less than (<); Units per liter (U/L), Marked abnormality Low (High): hemoglobin <6 (>18 females or >20 males) g/dL; creatinine (>=1.5*preRX, >=2.5 mg/dL); glucose < 54 or (> 350) mg/dL; albumin <= 2 or (> 6) g/dL; creatine kinase >5*ULN; albumin/creatinine ratio (>1800 mg/G); calcium <7.5 (>1 and >0.5 from PreRX) mg/dL; bicarbonate <=13 meq/dL; potassium <=2.5 (>6) meq/L; magnesium <1 (>4) mEq/L; sodium < 130 mEq/L (>150 mEq/L; phosphorus (>=5.6 mg/dL age 17-65, >=5.1 is >=66 years); Albumin/creatinine ratio (>1800 mg/g). Note: Hepatic tests are presented separately in next outcome measure.	Baseline (Day 1) to last dose double blind medication (Week 12) plus 4 days	Yes
Secondary	Number of Participants With Elevated Liver Laboratory Tests in Participants Treated With Double Blind 10 mg Dapagliflozin or Placebo , Including Data After Rescue	Laboratories were obtained at Day 1, Weeks 4, 8 and 12 in the Double Blind Period. Baseline: last assessment prior to start of first dose of double-blind treatment. Includes laboratory values measured after the first date of double-blind treatment and up to and including the last day of double blind treatment plus 30 days. Upper limit of normal (ULN);, alanine aminotransferase (ALT); aspartate aminotransferase (AST); alkaline phosphatase (ALP). Marked abnormality (High): AST and ALT (>3*ULN); ALP (>1.5*ULN); bilirubin (>1.5*ULN). Participants with abnormally elevated liver laboratory tests were followed 30 days after the last dose of study drug.	Baseline (Day 1) to last dose double blind medication (Week 12) Plus 30 days	Yes
Secondary	Number of Participants With Normal or Abnormal Electrocardiogram Summary Tracing at Week 12 (LOCF), Including Data After Rescue	12-Lead electrocardiograms (ECGs) were performed at Enrollment, Day 1 of Double Blind Period and Week 12/End of treatment visit (last observation carried forward) on participants who were supine. ECGs were assessed by the investigator as normal or abnormal. Baseline (BL) was Day 1 prior to dosing or last observation prior to dosing.	Baseline, Week 12	Yes
Secondary	Proportion of Participants With Orthostatic Hypotension at Baseline and Week 12, Including Data After Rescue	Orthostatic hypotension was defined as a decrease from supine to standing of > 20 mmHg in systolic BP or >10 mmHg in diastolic BP. Proportion was calculated from number of participants with orthostatic hypotension (n) divided by the number of treated participants (N). n/N presented as a percent (%). Baseline was Day 1 of the double blind Period. Measurements for orthostatic hypotension were taken on Day 1 and at Week 12 visit and does not reflect AEs reported by the investigator.	Baseline (Day 1), Week 12	Yes

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
•   Investigator Inquiry form