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
- Conditions
- Type 2 Diabetes
- Interventions
- Registration Number
- NCT01195662
- Lead Sponsor
- AstraZeneca
- Brief 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 2245
- 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
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dapagliflozin 10 mg Dapagliflozin Dapagliflozin 10 mg tablets Placebo matching Dapagliflozin Placebo matching Dapagliflozin Placebo tablets matching dapagliflozin tablets
- Primary Outcome Measures
Name Time Method Adjusted Mean Change From Baseline in Seated Systolic Blood Pressure for 12 Week Double-Blind Treatment Period - Randomized Participants Baseline to Week 12 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.
Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) for 12 Week Double-Blind Treatment Period - Randomized Participants Baseline to Week 12 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.
- Secondary Outcome Measures
Name Time Method Adjusted Mean Change From Baseline in 24-hour Ambulatory Systolic Blood Pressure at Week 12 Last Observation Carried Forward (LOCF) Baseline, Week 12 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.
Adjusted Mean Change From Baseline in Seated Diastolic Blood Pressure (DBP) for 12 Week Double-Blind Treatment Period - Randomized Participants Baseline to Week 12 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.
Adjusted Mean Change From Baseline in 24-hr Ambulatory Diastolic Blood Pressure at Week 12 (LOCF) Baseline, Week 12 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.
Adjusted Mean Change From Baseline in Serum Uric Acid at Week 12 in Double-Blind Treatment Period - Randomized Participants Baseline, Week 12 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.
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 Baseline to last dose of 12 weeks of double blind medication plus 30 days if SAE or plus 4 days if AE/hypoglycemic event 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.
Number of Participants With Marked Chemistry Laboratory Abnormalities in 12 Week Double Blind Treatment Period, Including Data After Rescue Baseline (Day 1) to last dose double blind medication (Week 12) plus 4 days 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.
Number of Participants With Elevated Liver Laboratory Tests in Participants Treated With Double Blind 10 mg Dapagliflozin or Placebo , Including Data After Rescue Baseline (Day 1) to last dose double blind medication (Week 12) Plus 30 days 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.
Number of Participants With Normal or Abnormal Electrocardiogram Summary Tracing at Week 12 (LOCF), Including Data After Rescue Baseline, Week 12 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.
Proportion of Participants With Orthostatic Hypotension at Baseline and Week 12, Including Data After Rescue Baseline (Day 1), Week 12 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.
Trial Locations
- Locations (155)
Abington Memorial Hos/Feasterville Family Health Care Center
🇺🇸Feasterville, Pennsylvania, United States
The Clinical Trial Center, Llc
🇺🇸Jenkintown, Pennsylvania, United States
Research Across America
🇺🇸Reading, Pennsylvania, United States
Pish Medical Associates
🇺🇸Uniontown, Pennsylvania, United States
Greater Providence Clinical Research, Llc
🇺🇸Warwick, Rhode Island, United States
North Myrtle Beach Family Practice
🇺🇸North Myrtle Beach, South Carolina, United States
Southwind Medical Specialists
🇺🇸Memphis, Tennessee, United States
Integrated Research Group, Inc.
🇺🇸Riverside, California, United States
Mcs Clinical Trials
🇺🇸Los Angeles, California, United States
Clinical Research Advantage/Desert Clinical Research
🇺🇸Tempe, Arizona, United States
Neurological Research Institute
🇺🇸Santa Monica, California, United States
Orange County Research Center
🇺🇸Tustin, California, United States
Orrin M. Troum, Md And Medical Associates
🇺🇸Santa Monica, California, United States
International Research Associates, Llc
🇺🇸Hialeah, Florida, United States
University Clinical Investigators, Inc.
🇺🇸Tustin, California, United States
Palm Springs Research Institute
🇺🇸Hialeah, Florida, United States
Central Florida Internists
🇺🇸Kissimmee, Florida, United States
River Birch Research Alliance, Llc
🇺🇸Blue Ridge, Georgia, United States
Medical Development Centers, Llc
🇺🇸Baton Rouge, Louisiana, United States
Philadelphia Health Associates - Adult Medicine
🇺🇸Philadelphia, Pennsylvania, United States
Perimeter Institute For Clinical Research
🇺🇸Atlanta, Georgia, United States
Clinical Research Of Miami, Inc.
🇺🇸Miami, Florida, United States
Flcri Global Research, Llc
🇺🇸Miami, Florida, United States
Pharmax Research Clinic, Inc.
🇺🇸Miami, Florida, United States
Community Research Foundation, Inc.
🇺🇸Miami, Florida, United States
Baptist Diabetes Associates, Pa
🇺🇸Miami, Florida, United States
3rd Coast Research Associates
🇺🇸Corpus Christi, Texas, United States
Wetlin Research Associates, Inc.
🇺🇸San Diego, California, United States
Office Of Ted Thorp, Md
🇺🇸Las Vegas, Nevada, United States
Independent Clinical Researchers@ Wolfson Medical Center
🇺🇸Las Vegas, Nevada, United States
Clinical Research Advantage, Inc.
🇺🇸Las Vegas, Nevada, United States
Palm Medical Research Center
🇺🇸Las Vegas, Nevada, United States
Community Research
🇺🇸Cincinnati, Ohio, United States
Krk Medical Research
🇺🇸Dallas, Texas, United States
Renaissance Clinical Research And Hypertension Pllc
🇺🇸Dallas, Texas, United States
Internal Medicine Clinical Reaseach
🇺🇸Dallas, Texas, United States
Sergio F. Rovner, M.D.
🇺🇸El Paso, Texas, United States
Pioneer Research Solutions, Inc.
🇺🇸Houston, Texas, United States
Lisa E. Medwedeff, Md, Pa
🇺🇸Plano, Texas, United States
Exodus Healthcare Network
🇺🇸Magna, Utah, United States
Manassas Clinical Research Center
🇺🇸Manassas, Virginia, United States
Lillestol Research
🇺🇸Fargo, North Dakota, United States
Phillips Medical Services, Pllc
🇺🇸Jackson, Mississippi, United States
Preferred Research Partners, Inc.
🇺🇸Little Rock, Arkansas, United States
Southeastern Research Associates, Inc.
🇺🇸Greenville, South Carolina, United States
Visions Clinical Research - Tucson
🇺🇸Tucson, Arizona, United States
The Center For Clinical Trials
🇺🇸Biloxi, Mississippi, United States
Aureus Research, Inc.
🇺🇸Little Rock, Arkansas, United States
Comprehensive Clinical Research
🇺🇸Berlin, New Jersey, United States
Christiana Care Health Services, Inc
🇺🇸Newark, Delaware, United States
Hillcrest Clinical Reseach, Llc
🇺🇸Simpsonville, South Carolina, United States
Tn Medical Research
🇺🇸Spring Hill, Tennessee, United States
Pawleys Pediatrics And Adult Medicine
🇺🇸Pawleys Island, South Carolina, United States
Clin Research Advantage, Inc. James Meli, Do Family Pracice
🇺🇸Henderson, Nevada, United States
Dependable Clinical Research, Llc
🇺🇸Houston, Texas, United States
Palmetto Clinical Research
🇺🇸Summerville, South Carolina, United States
Arlington Family Research Center, Inc.
🇺🇸Arlington, Texas, United States
Hill Country Medical Associates
🇺🇸New Braunfels, Texas, United States
Research Institute Of Dallas
🇺🇸Dallas, Texas, United States
Village Family Practice
🇺🇸Houston, Texas, United States
North Hills Medical Research, Inc.
🇺🇸North Richland Hills, Texas, United States
Med-Olam Clinical Research
🇺🇸Pasadena, Texas, United States
Bellaire Medical Care Group
🇺🇸Houston, Texas, United States
Breco Research, Ltd
🇺🇸Sugarland, Texas, United States
Millennium Clinical Trials Llc
🇺🇸Arlington, Virginia, United States
Burke Internal Medicine And Research
🇺🇸Burke, Virginia, United States
Hampton Roads Center For Clinical Research, Inc.
🇺🇸Suffolk, Virginia, United States
Local Institution
🇬🇧Bath, Wiltshire, United Kingdom
Eclipse Clinical Research
🇺🇸Tucson, Arizona, United States
Medical Affiliated Research Center, Inc.
🇺🇸Huntsville, Alabama, United States
Bayview Research Group, Llc
🇺🇸Paramount, California, United States
Central Phoenix Medical Center
🇺🇸Tempe, Arizona, United States
Clinical Research Advantage, Inc./Mesa Family Med Ctr, Pc
🇺🇸Tempe, Arizona, United States
Cmp Research
🇺🇸Anaheim, California, United States
Randall G. Shue, D.O.
🇺🇸Los Angeles, California, United States
Catalina Research Institute, Llc
🇺🇸Chino, California, United States
Sds Clinical Trials
🇺🇸Orange, California, United States
Southland Clinical Research Center, Inc.
🇺🇸Fountain Valley, California, United States
Clinica Medica San Miguel
🇺🇸Los Angeles, California, United States
National Research Inst
🇺🇸Los Angeles, California, United States
Time Clinical Research Inc.
🇺🇸Huntington Park, California, United States
Torrance Clinical Research
🇺🇸Torrance, California, United States
San Diego Managed Care Group
🇺🇸Poway, California, United States
Ocean Blue Medical Research Center, Inc.
🇺🇸Miami Springs, Florida, United States
Crest Clinical Trials, Inc.
🇺🇸Santa Ana, California, United States
Chase Medical Research, Llc
🇺🇸Waterbury, Connecticut, United States
Innovative Research Of West Florida, Inc
🇺🇸Clearwater, Florida, United States
Zasa Clinical Research
🇺🇸Boynton Beach, Florida, United States
So. Illinois Clin Res Ctr @ Div Of Kevin L Pritchett Md, Pc
🇺🇸O?Fallon, Illinois, United States
The Community Research Of South Florida
🇺🇸Hialeah, Florida, United States
Newphase Clinical Trials, Inc.
🇺🇸Miami Beach, Florida, United States
Acadia Clinical Research, Llc
🇺🇸Bangor, Maine, United States
Bainbridge Medical Associates
🇺🇸Bainbridge, Georgia, United States
Suncoast Clinical Research, Inc.
🇺🇸New Port Richey, Florida, United States
In-Quest Medical Research, Llc
🇺🇸Duluth, Georgia, United States
Cedar Crosse Research Center
🇺🇸Chicago, Illinois, United States
American Health Network Of In Llc
🇺🇸Muncie, Indiana, United States
Hci-Metromedic Walk-In Medical Office
🇺🇸New Bedford, Massachusetts, United States
Middle Georgia Drug Study Center, Llc
🇺🇸Perry, Georgia, United States
Springfield Diabetes And Endocrine Center
🇺🇸Springfield, Illinois, United States
Community Health Care, Inc.
🇺🇸Canal Fulton, Ohio, United States
American Health Network Of Indiana Llc
🇺🇸Avon, Indiana, United States
Laporte County Institute For Clinical Research, Inc.
🇺🇸Michigan City, Indiana, United States
Omega Clinical Research, Llc
🇺🇸Metairie, Louisiana, United States
Investigators Research Group, Llc
🇺🇸Brownsburg, Indiana, United States
Providence Park Clinical Research
🇺🇸Novi, Michigan, United States
Neurocare, Inc.
🇺🇸Newton, Massachusetts, United States
Southgate Medical Group
🇺🇸West Seneca, New York, United States
Atlantic Clinical Trials, Llc
🇺🇸Watertown, Massachusetts, United States
Medex Healthcare Research, Inc.
🇺🇸New York, New York, United States
Clinical Research Source, Inc
🇺🇸Perrysburg, Ohio, United States
Parsons Avenue Medical Clinical
🇺🇸Columbus, Ohio, United States
Southwest Clinical Trials
🇺🇸Houston, Texas, United States
Excel Clinical Research, Llc
🇺🇸Houston, Texas, United States
Arcuri Clinical Research Llc
🇺🇸Philadelphia, Pennsylvania, United States
University Of Alabama At Birmingham
🇺🇸Birmingham, Alabama, United States
43rd Medical Associates
🇺🇸Phoenix, Arizona, United States
Sooner Clinical Research
🇺🇸Oklahoma City, Oklahoma, United States
Sun Research Institute
🇺🇸San Antonio, Texas, 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
Wasatch Endocrinology And Diabetes Specialists
🇺🇸Salt Lake City, Utah, United States
Wasatch Clinical Research
🇺🇸Salt Lake City, Utah, United States
Jefferson City Medical Group
🇺🇸Jefferson City, Missouri, United States
Apf Research, Llc
🇺🇸Miami, Florida, United States
Alexandria Health Care Center
🇺🇸Alexandria, Virginia, United States
Sound Medical Research
🇺🇸Port Orchard, Washington, United States
Larry D. Stonesifer, Md
🇺🇸Federal Way, Washington, United States
Clinical Investigation Specialists, Inc.
🇺🇸Kenosha, Wisconsin, United States
Wilmax Clinical Research, Inc.
🇺🇸Mobile, Alabama, United States
Del Rosario Medical Clinic, Inc.
🇺🇸Huntington Park, California, United States
Marin Endocrine Care & Research, Inc.
🇺🇸Greenbrae, California, United States
American Institute Of Research
🇺🇸Los Angeles, California, 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
Bradenton Research Center, Inc.
🇺🇸Bradenton, Florida, United States
Clinical Research Of South Florida
🇺🇸Coral Gables, Florida, United States
Michele A. Morrison Internal Medicine, Inc.
🇺🇸Pembroke Pines, Florida, United States
Avail Clinical Research, Llc
🇺🇸Deland, Florida, United States
Medsol Clinical Research Center
🇺🇸Port Charlotte, Florida, United States
Digiovanna Institute For Medical Education & Research
🇺🇸North Massapequa, New York, United States
Diabetes & Endocrinology Consultants
🇺🇸Morehead City, North Carolina, United States
Burke Primary Care
🇺🇸Morganton, North Carolina, United States
Willamette Valley Clinical Studies
🇺🇸Eugene, Oregon, United States
Southeastern Pa Medical Institute
🇺🇸Broomall, Pennsylvania, United States
Florida Institute For Clinical Research, Llc
🇺🇸Orlando, Florida, United States
Meridien Research
🇺🇸Tampa, Florida, United States
Kcumb Dybedal Clinical Research Center
🇺🇸Kansas City, Missouri, United States
Medical Research South
🇺🇸Charleston, South Carolina, United States
Quality Control Research, Inc
🇺🇸Sacramento, California, United States
Alternative Primary Care
🇺🇸Silver Spring, Maryland, United States
Premier Research
🇺🇸Trenton, New Jersey, United States
Integris Family Care Yukon
🇺🇸Yukon, Oklahoma, United States