Safety and Efficacy of Dapagliflozin as Monotherapy in Subjects With Type 2 Diabetes

Type 2 Diabetes Mellitus Clinical Trial

Official title:

A Multicenter, Randomized, Double-Blind, Placebo Controlled, Parallel Group, Phase III Trial to Evaluate the Safety and Efficacy of Dapagliflozin as Monotherapy in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control With Diet and Exercise

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00736879
• Other study ID #: MB102-032
• Status: Completed
• Phase: Phase 3
• First received: August 15, 2008
• Last updated: April 18, 2017
• Start date: September 22, 2008
• Est. completion date: December 29, 2009

Study information

• Verified date: April 2017
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this clinical research study is to learn if BMS-512148 (Dapagliflozin) can help reduce the blood sugar levels in subjects with Type 2 Diabetes who are not well controlled on diet and exercise alone. The safety of this treatment will also be studied

Recruitment information / eligibility

• Status: Completed
• Enrollment: 497
• Est. completion date: December 29, 2009
• Est. primary completion date: December 29, 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 77 Years

Eligibility

Inclusion Criteria:

• Male and females, =18 to =77 years old, with type 2 diabetes mellitus

• Subjects must have central laboratory pre-randomization A1C =7.0 and = 10.0%

• C-peptide = 1.0 ng/mL (0.34 nmol/L)

• Body Mass Index = 45 kg/m²

• Must be able to perform self monitoring of blood glucose

Exclusion Criteria:

• aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3* upper limit of normal (ULN)

• Serum Total bilirubin >2 mg/dL (34.2 µmol/L)

• Creatinine kinase >3* ULN

• Serum creatinine =1.50 mg/dL (133 µmol/L) for male subjects, =1.40 mg/dL (124 µmol/L) for female subjects

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Dapagliflozin
Tablets, Oral, Once Daily, Up to 24 weeks
• Placebo
Tablets, Oral, Once Daily, Up to 24 weeks

Locations

Country	Name	City	State
Canada	Local Institution	Ajax	Ontario
Canada	Local Institution	Bathurst	New Brunswick
Canada	Local Institution	Calgary	Alberta
Canada	Local Institution	Coquitlam	British Columbia
Canada	Local Institution	Drummondville	Quebec
Canada	Local Institution	L'Ancienne Lorette	Quebec
Canada	Local Institution	St-Leonard	Quebec
Canada	Local Institution	Toronto	Ontario
Canada	Local Institution	Waterloo	Ontario
Canada	Local Institution	Winnipeg	Manitoba
India	Local Institution	Ahmedabad
India	Local Institution	Bangalore
India	Local Institution	Bangalore
India	Local Institution	Jaipur
India	Local Institution	Jaipur
Mexico	Local Institution	Df	Distrito Federal
Mexico	Local Institution	Durango
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Merida	Yucatan
Mexico	Local Institution	Mexico City
Mexico	Local Institution	Monterrey	Nuevo Leon
Mexico	Local Institution	Veracruz
Puerto Rico	Local Institution	Ponce
Puerto Rico	Local Institution	Ponce
Russian Federation	Local Institution	Kursk
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	St. Petersburg
Russian Federation	Local Institution	St.Petersburg
South Africa	Local Institution	Benoni	Gauteng
South Africa	Local Institution	Paarl	Western Cape
South Africa	Local Institution	Soweto	Gauteng
South Africa	Local Institution	Tygerberg	Western Cape
United States	James J. Brown, Md	Akron	Ohio
United States	Central Florida Clinical Trials, Inc.	Altamonte Springs	Florida
United States	Belzoni Clinical Research	Belzoni	Mississippi
United States	Valley Research	Fresno	California
United States	Family Physicians Of Greeley	Greeley	Colorado
United States	R-Research	Hamilton	New Jersey
United States	Westside Center For Clinical Research	Jacksonville	Florida
United States	Dedicated Clinical Research	Litchfield Park	Arizona
United States	Marina Raikhel, Md, Faafp	Lomita	California
United States	Richard S. Cherlin, Md	Los Gatos	California
United States	Panhandle Family Care Associates	Marianna	Florida
United States	Avastra Clinical Trials	Midvale	Utah
United States	Down East Medical Associates, Pa	Morehead City	North Carolina
United States	Coastal Connecticut Research, Llc	New London	Connecticut
United States	Integris Family Care South	Oklahoma	Oklahoma
United States	Capital Clinical Research Center	Olympia	Washington
United States	43rd Medical Associates, P.C.	Phoenix	Arizona
United States	Endocrine Research Solutions, Inc.	Roswell	Georgia
United States	Optimum Clinical Research, Inc.	Salt Lake City	Utah
United States	Abbott Clinical Research Group, Inc	San Antonio	Texas
United States	Stephen G. Danley, Do	Spokane	Washington
United States	Internist Associates Of Central New York	Syracuse	New York
United States	Southeastern Research Associates, Inc.	Taylors	South Carolina
United States	Clinical Research Advantage, Inc.	Tempe	Arizona
United States	Orange County Research Center	Tustin	California
United States	Southgate Medical Group	West Seneca	New York

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Canada,  India,  Mexico,  Puerto Rico,  Russian Federation,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) at Week 24 Last Observation Carried Forward (LOCF) - All Randomized Participants	Adjusted mean change in HbA1c from baseline at Week 24, or the last post-baseline measurement prior to Week 24 if no Week 24 assessment was available was determined(LOCF). HbA1c was measured as percent of hemoglobin by a central laboratory. Data after rescue medication (metformin) was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. HbA1c values were obtained at enrollment, lead-in, and at Day 1, Weeks 4, 8, 12, 16, 20, and 24 in the double-blind period.	Baseline (Day 1), Week 24
Secondary	Adjusted Mean Change From Baseline in Total Body Weight at Week 24 (LOCF) - Randomized Participants	Adjusted mean change in total body weight from baseline at Week 24, or the last post-baseline measurement prior to Week 24 if no Week 24 assessment was available LOCF was determined. Data after rescue medication (metformin) was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Body weight was measured in kilograms (kg) at qualification, lead-in, Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, and 24 during double-blind period.	Baseline (Day 1), Week 24
Secondary	Adjusted Mean Change From Baseline in Fasting Plasma Glucose at Week 24 (LOCF) - Randomized Participants	Adjusted mean change in fasting plasma glucose (FPG) from baseline at Week 24 (LOCF) was determined. Data after rescue medication (metformin) was excluded from this analysis. FPG was measured as milligrams per deciliter (mg/dL) by a central laboratory at qualification, lead-in, Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, and 24 during double-blind period. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication.	Baseline (Day 1), Week 24
Secondary	Adjusted Mean Change From Baseline in Effect on 2-hour Post Liquid Meal Glucose at Week 24 (LOCF) - Randomized Participants	Liquid meal tolerance tests (MTTs) were scheduled to occur at Day 1 visit (MTT was to be completed 2 hours prior to first dose of treatment) and at Week 24 / End of treatment visit, or Rescue visit for participants meeting criteria for rescue due to lack of glycemic control. At Week 24, study treatment was given 1 hour before MTT was administered. Participant fasted for at least 10 hours (h) prior to both visits and abstained from tobacco, alcohol, and caffeine for 24 h prior to the MTT. The liquid meal supplement was administered over 10 minutes, starting immediately after Time 0 blood sample was drawn. Blood samples for post-liquid meal Glucose were obtained at 30, 60, 120, and 180 minutes after ingesting the liquid supplement. Glucose 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 double-blind study medication.	Baseline (Day 1), Week 24
Secondary	Adjusted Percentage of Participants Achieving a Therapeutic Glycemic Response at Week 24 (LOCF) - Randomized Participants	Therapeutic glycemic response was defined as HbA1c less than 7.0%. n=Number of participants with HBA1c less than (<) 7 % at Week 24, last observation carried forward (LOCF) while N=number of randomized participants with non-missing baseline and Week 24 (LOCF) values. Percent=n/N and was adjusted for Baseline HbA1c. Data after rescue medication (metformin) was excluded from this analysis. HbA1c was measured as a percent of hemoglobin.	Baseline (Day 1), Week 24
Secondary	Adjusted Mean Change From Baseline in Waist Circumference at Week 24 (LOCF) - Randomization Participants	Adjusted mean waist circumference values from baseline to Week 24 (or the last post-baseline measurement prior to Week 24 if no Week 24 assessment was available, last observation carried forward, (LOCF) was determined. Data after rescue medication (metformin) was excluded from this analysis. Waist circumference was measured centimeters (cm) and obtained at lead-in, Day 1, and Week 24 of the double-blind period. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication.	Baseline (Day 1), Week 24
Secondary	Number of Participants With Deaths, Serious AEs (SAEs), Adverse Events (AEs), Discontinuation Due to AEs, During the 12 Week Double Blind Period, Including Data After Rescue - All Treated Participants	Medical Dictionary for Regulatory Activities (MedDRA), version 12.1 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. Treatment-related=having certain, probable, possible, or missing relationship to study drug as per the investigator. Baseline to last dose plus 4 days for AEs, plus 30 days for SAEs. Data after rescue included.	Day 1 of Double Blind Period to end of Week 24 Plus 30 days
Secondary	Number of Participants With Adverse Events of Special Interest During the 12 Week Double Blind Period - All Treated Participants	Participants with AEs of hypoglycemia, cardiac/vascular disorders, renal impairment or failure, volume depletion (hypotension/dehydration/hypovolemia), fractures, urinary stones, and other reports suggestive of genital infection or urinary tract infection (UTI) were summarized using MedDRA version 12.1. Data after rescue included for all AEs of special interest except hypoglycemia; hypoglycemia AEs were prior to rescue. Major hypoglycemic episode: symptomatic requiring 3rd party assistance due to severe impairment in consciousness or behavior with a glucose value < 54 mg/dL and prompt recovery after glucose/glucagon; Minor: either symptomatic with glucose measurement < 63 mg/dL, regardless of need for 3rd party assistance, or asymptomatic with glucose < 63 mg/dL that does not qualify as major; Other: suggestive but not meeting criteria for major or minor.	Baseline to last dose plus 4 days in 12 Week Double Blind Period
Secondary	Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure at Week 24, Including Data After Rescue - Treated Participants	Blood pressure values were obtained on Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, and 24 in the double blind period, after the participant was seated for quietly for 5 minutes; the same arm (right or left) was used consistently through out the study. Measurements were taken at least 10 hours after the last ingestion of caffeine, alcohol, or nicotine. Blood pressure was measured in millimeters of mercury (mmHg). Data after rescue were also included. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication.	Baseline (Day 1), Week 24
Secondary	Mean Change From Baseline in Seated Heart Rate at Week 24 - Treated Participants	Heart rate values were obtained after the participant was seated for quietly for 5 minutes; the same arm (right or left) was used consistently through out the study. Measurements were taken at least 10 hours after the last ingestion of caffeine, alcohol, or nicotine. Heart rate was measured in beats per minute (bpm). Data after rescue were also included. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication.	Baseline (Day 1), Week 24
Secondary	Number of Participants With Normal or Abnormal Electrocardiogram Summary Tracing at Week 24 (LOCF) - Treated Participants	12-Lead electrocardiograms (ECGs) were performed at Day -14 and Week 24/End of treatment visit (last observation carried forward) on participants who were supine. ECGs were assessed by the investigator. Baseline (BL) was Day -14 for this parameter.	Week 24
Secondary	Number of Participants With Marked Laboratory Abnormalities in 24 Week Double Blind Treatment Period - Treated Participants	Safety laboratory measurements were obtained at Day 1, Weeks 1, 2, 4, 8, 12, 20, and 24 in the double blind Period. Baseline was defined as the last assessment prior to the start of the first dose of the double-blind study medication. Data included from baseline up to and including the last day of treatment plus 4 days. Data after rescue was also included. Abbreviations; 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), alanine aminotransferase (ALT); aspartate aminotransferase (AST); alkaline phosphatase (ALP); blood urea nitrogen (BUN). Marked abnormality Low (High) defined: hemoglobin <6 (>18 females or >20 males) g/dL; hematocrit <20% ( >55% females or >60% males); BUN (>60 mg/dL) or Urea >21.4 mmol/L; creatinine (>=1.5*preRX, >=2.5 mg/dL); AST and ALT >3*ULN; bilirubin >1.5*ULN; ALP >1.5*ULN.	Baseline to Week 24/end of treatment plus 4 days

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   Investigator Inquiry form