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A Phase III Study of BMS-512148 (Dapagliflozin) in Asian Patients With Type 2 Diabetes Who Are Not Well Controlled With Diet and Exercise

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ClinicalTrials.gov Identifier: NCT01095653
Recruitment Status : Completed
First Posted : March 30, 2010
Results First Posted : February 6, 2017
Last Update Posted : February 6, 2017
Sponsor:
Collaborator:
AstraZeneca, Bristol-Myers Squibb
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Type 2 Diabetes
Interventions Drug: Dapagliflozin
Drug: Metformin
Drug: Dapagliflozin Placebo
Enrollment 1179
Recruitment Details Of 1179 participants enrolled, 514 completed a qualification period. Of these 514 participants, 393 were randomized and received treatment. Of these 393 participants, 343 completed double-blind treatment period.
Pre-assignment Details  
Arm/Group Title Placebo Dapagliflozin 5 mg Dapagliflozin 10 mg
Hide Arm/Group Description Participants received dapagliflozin matching placebo once daily for up to 24 weeks (may include the addition of open-label metformin as rescue) Participants received dapagliflozin 5 mg once daily for up to 24 weeks (may include the addition of open-label metformin as rescue) Participants received dapagliflozin 10 mg once daily for up to 24 weeks (may include the addition of open-label metformin as rescue)
Period Title: Overall Study
Started 132 128 133
Completed 113 113 117
Not Completed 19 15 16
Reason Not Completed
Lack of Efficacy             3             0             0
Adverse Event             1             4             4
Lost to Follow-up             1             0             4
Withdrawal by Subject             4             5             3
non-compliance, not met criteria, etc.             10             6             5
Arm/Group Title Placebo Dapagliflozin 5 mg Dapagliflozin 10 mg Total
Hide Arm/Group Description Participants received dapagliflozin matching placebo once daily for up to 24 weeks (may include the addition of open-label metformin as rescue) Participants received dapagliflozin 5 mg once daily for up to 24 weeks (may include the addition of open-label metformin as rescue) Participants received dapagliflozin 10 mg once daily for up to 24 weeks (may include the addition of open-label metformin as rescue) Total of all reporting groups
Overall Number of Baseline Participants 132 128 133 393
Hide Baseline Analysis Population Description
All randomized participants who received at least 1 dose of study medication
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 132 participants 128 participants 133 participants 393 participants
49.9  (10.87) 53.0  (11.07) 51.2  (9.89) 51.3  (10.67)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 132 participants 128 participants 133 participants 393 participants
Younger than 65 years 120 108 123 351
65 to younger than 75 years 11 14 10 35
75 years and older 1 6 0 7
Sex/Gender, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 132 participants 128 participants 133 participants 393 participants
Male 87 84 86 257
Female 45 44 47 136
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 132 participants 128 participants 133 participants 393 participants
ASIAN INDIAN 8 8 9 25
CHINESE 117 114 117 348
JAPANESE 1 0 1 2
KOREAN 5 6 5 16
ASIAN OTHER 1 0 1 2
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 132 participants 128 participants 133 participants 393 participants
72.18  (13.234) 68.89  (11.429) 70.92  (11.637) 70.68  (12.177)
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 132 participants 128 participants 133 participants 393 participants
25.93  (3.644) 25.17  (3.285) 25.76  (3.434) 25.62  (3.465)
1.Primary Outcome
Title Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24 (Last Observation Carried Forward [LOCF])
Hide Description HbA1c was measured as percent of hemoglobin by a central laboratory. Data after rescue medication 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 measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 4, 8, 12, 16, 20, and 24 in the double-blind period.
Time Frame From Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received study medication and had nonmissing HbA1c values at baseline and Week 24 (LOCF)
Arm/Group Title Placebo Dapagliflozin 5 mg Dapagliflozin 10 mg
Hide Arm/Group Description:
Participants received dapagliflozin matching placebo once daily for up to 24 weeks (may include the addition of open-label metformin as rescue)
Participants received dapagliflozin 5 mg once daily for up to 24 weeks (may include the addition of open-label metformin as rescue)
Participants received dapagliflozin 10 mg once daily for up to 24 weeks (may include the addition of open-label metformin as rescue)
Overall Number of Participants Analyzed 127 122 127
Mean (Standard Error)
Unit of Measure: % of hemoglobin
-0.29  (0.0681) -1.04  (0.0695) -1.11  (0.0680)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Dapagliflozin 5 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Primary endpoints were tested at alpha=0.027 applying Dunnett’s adjustment
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.75
Confidence Interval (2-Sided) 95%
-0.94 to -0.56
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0975
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Dapagliflozin 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Primary endpoints were tested at alpha=0.027 applying Dunnett’s adjustment
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.82
Confidence Interval (2-Sided) 95%
-1.01 to -0.63
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0962
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 (Last Observation Carried Forward [LOCF])
Hide Description Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Fasting plasma glucose was measured as 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. 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. FPG measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 1, 2, 4, 8, 12, 16, 20, and 24 in the double-blind period.
Time Frame From Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received study medication and had nonmissing FPG values at baseline and Week 24 (LOCF)
Arm/Group Title Placebo Dapagliflozin 5 mg Dapagliflozin 10 mg
Hide Arm/Group Description:
Participants received dapagliflozin matching placebo once daily for up to 24 weeks (may include the addition of open-label metformin as rescue)
Participants received dapagliflozin 5 mg once daily for up to 24 weeks (may include the addition of open-label metformin as rescue)
Participants received dapagliflozin 10 mg once daily for up to 24 weeks (may include the addition of open-label metformin as rescue)
Overall Number of Participants Analyzed 131 127 128
Mean (Standard Error)
Unit of Measure: mg/dL
2.5  (2.237) -25.1  (2.274) -31.6  (2.255)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Dapagliflozin 5 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Secondary endpoints were tested following a sequential testing procedure at alpha=0.05
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -27.7
Confidence Interval (2-Sided) 95%
-34.0 to -21.4
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.203
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Dapagliflozin 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Secondary endpoints were tested following a sequential testing procedure at alpha=0.05
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -34.2
Confidence Interval (2-Sided) 95%
-40.4 to -27.9
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.174
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Adjusted Mean Change From Baseline in 2-hour Post Liquid Meal Glucose (PLMG) (mg/dL) at Week 24 (Last Observation Carried Forward [LOCF])
Hide Description Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Post Liquid Meal Glucose was measured as 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. 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. PLMG measurements were obtained on Day 1 and week 24 in the double-blind period.
Time Frame From Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received study medication and had nonmissing PLMG values at baseline and Week 24 (LOCF)
Arm/Group Title Placebo Dapagliflozin 5 mg Dapagliflozin 10 mg
Hide Arm/Group Description:
Participants received dapagliflozin matching placebo once daily for up to 24 weeks (may include the addition of open-label metformin as rescue)
Participants received dapagliflozin 5 mg once daily for up to 24 weeks (may include the addition of open-label metformin as rescue)
Participants received dapagliflozin 10 mg once daily for up to 24 weeks (may include the addition of open-label metformin as rescue)
Overall Number of Participants Analyzed 105 100 105
Mean (Standard Error)
Unit of Measure: mg/dL
1.08  (4.5663) -46.8  (4.6559) -54.9  (4.5257)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Dapagliflozin 5 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Secondary endpoints were tested following a sequential testing procedure at alpha=0.05
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -47.9
Confidence Interval (2-Sided) 95%
-60.80 to -34.96
Parameter Dispersion
Type: Standard Error of the mean
Value: 6.5667
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Dapagliflozin 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Secondary endpoints were tested following a sequential testing procedure at alpha=0.05
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -56.0
Confidence Interval (2-Sided) 95%
-68.66 to -43.28
Parameter Dispersion
Type: Standard Error of the mean
Value: 6.4489
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Adjusted Mean Change From Baseline in Total Body Weight (kg) at Week 24 (Last Observation Carried Forward [LOCF])
Hide Description Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Adjusted mean change from baseline in total body weight at Week 24 (or the last postbaseline measurement prior to Week 24 if no Week 24 assessment was available was determined. Data after rescue medication 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 measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 1, 2, 4, 8, 12, 16, 20, and 24 of the double-blind period.
Time Frame From Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received study medication and had nonmissing body weight values at baseline and Week 24 (LOCF)
Arm/Group Title Placebo Dapagliflozin 5 mg Dapagliflozin 10 mg
Hide Arm/Group Description:
Participants received dapagliflozin matching placebo once daily for up to 24 weeks (may include the addition of open-label metformin as rescue)
Participants received dapagliflozin 5 mg once daily for up to 24 weeks (may include the addition of open-label metformin as rescue)
Participants received dapagliflozin 10 mg once daily for up to 24 weeks (may include the addition of open-label metformin as rescue)
Overall Number of Participants Analyzed 132 128 128
Mean (Standard Error)
Unit of Measure: kg
-0.27  (0.2279) -1.64  (0.2315) -2.25  (0.2308)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Dapagliflozin 5 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Secondary endpoints were tested following a sequential testing procedure at alpha=0.05
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.37
Confidence Interval (2-Sided) 95%
-2.01 to -0.73
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.3259
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Dapagliflozin 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Secondary endpoints were tested following a sequential testing procedure at alpha=0.05
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.98
Confidence Interval (2-Sided) 95%
-2.62 to -1.34
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.3242
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 24 (Last Observation Carried Forward [LOCF])
Hide Description Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Percent adjusted for baseline HbA1c. Therapeutic glycemic response is defined as HbA1c <7.0%. Data after rescue medication was excluded from this analysis. HbA1c was measured as a percent of hemoglobin. Mean and standard error for percentage of participants were estimated by modified logistic regression model.
Time Frame From Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received study medication and had nonmissing values at baseline and Week 24 (LOCF)
Arm/Group Title Placebo Dapagliflozin 5 mg Dapagliflozin 10 mg
Hide Arm/Group Description:
Participants received dapagliflozin matching placebo once daily for up to 24 weeks (may include the addition of open-label metformin as rescue)
Participants received dapagliflozin 5 mg once daily for up to 24 weeks (may include the addition of open-label metformin as rescue)
Participants received dapagliflozin 10 mg once daily for up to 24 weeks (may include the addition of open-label metformin as rescue)
Overall Number of Participants Analyzed 127 122 127
Mean (Standard Error)
Unit of Measure: Percentage of participants
21.3  (3.310) 42.6  (4.300) 49.8  (4.032)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Dapagliflozin 5 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Secondary endpoints were tested following a sequential testing procedure at alpha=0.05
Method Modified logistic regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 21.3
Confidence Interval (2-Sided) 95%
11.1 to 31.6
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.238
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Dapagliflozin 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Secondary endpoints were tested following a sequential testing procedure at alpha=0.05
Method Modified logistic regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 28.5
Confidence Interval (2-Sided) 95%
18.6 to 38.3
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.022
Estimation Comments [Not Specified]
Time Frame Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 24 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Dapagliflozin 5 mg Dapagliflozin 10 mg
Hide Arm/Group Description Participants received dapagliflozin matching placebo once daily for up to 24 weeks (may include the addition of open-label metformin as rescue) Participants received dapagliflozin 5 mg once daily for up to 24 weeks (may include the addition of open-label metformin as rescue) Participants received dapagliflozin 10 mg once daily for up to 24 weeks (may include the addition of open-label metformin as rescue)
All-Cause Mortality
Placebo Dapagliflozin 5 mg Dapagliflozin 10 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Dapagliflozin 5 mg Dapagliflozin 10 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/132 (1.52%)      5/128 (3.91%)      4/133 (3.01%)    
Cardiac disorders       
MYOCARDIAL INFARCTION  1  1/132 (0.76%)  1 0/128 (0.00%)  0 0/133 (0.00%)  0
Congenital, familial and genetic disorders       
PYLORIC STENOSIS  1  0/132 (0.00%)  0 0/128 (0.00%)  0 1/133 (0.75%)  1
Endocrine disorders       
GOITRE  1  0/132 (0.00%)  0 1/128 (0.78%)  1 1/133 (0.75%)  1
Gastrointestinal disorders       
GASTRIC ULCER  1  0/132 (0.00%)  0 0/128 (0.00%)  0 1/133 (0.75%)  1
Hepatobiliary disorders       
CHOLECYSTITIS  1  0/132 (0.00%)  0 1/128 (0.78%)  1 0/133 (0.00%)  0
CHOLECYSTITIS ACUTE  1  1/132 (0.76%)  1 0/128 (0.00%)  0 0/133 (0.00%)  0
Infections and infestations       
URETHRITIS  1  0/132 (0.00%)  0 0/128 (0.00%)  0 1/133 (0.75%)  1
Injury, poisoning and procedural complications       
ANKLE FRACTURE  1  0/132 (0.00%)  0 1/128 (0.78%)  1 0/133 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
PANCREATIC CARCINOMA  1  0/132 (0.00%)  0 1/128 (0.78%)  1 0/133 (0.00%)  0
Nervous system disorders       
LACUNAR INFARCTION  1  0/132 (0.00%)  0 0/128 (0.00%)  0 1/133 (0.75%)  1
CEREBRAL INFARCTION  1  0/132 (0.00%)  0 2/128 (1.56%)  2 0/133 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA Version: 15.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Dapagliflozin 5 mg Dapagliflozin 10 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   38/132 (28.79%)      28/128 (21.88%)      23/133 (17.29%)    
Infections and infestations       
UPPER RESPIRATORY TRACT INFECTION  1  12/132 (9.09%)  13 10/128 (7.81%)  10 9/133 (6.77%)  13
NASOPHARYNGITIS  1  5/132 (3.79%)  5 7/128 (5.47%)  8 4/133 (3.01%)  6
Metabolism and nutrition disorders       
HYPERLIPIDAEMIA  1  14/132 (10.61%)  14 10/128 (7.81%)  10 9/133 (6.77%)  9
DYSLIPIDAEMIA  1  7/132 (5.30%)  7 3/128 (2.34%)  3 2/133 (1.50%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA Version: 15.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Anna Maria Langkilde
Organization: AstraZeneca
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01095653     History of Changes
Other Study ID Numbers: MB102-054
First Submitted: March 26, 2010
First Posted: March 30, 2010
Results First Submitted: September 30, 2016
Results First Posted: February 6, 2017
Last Update Posted: February 6, 2017