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A Phase III Study of BMS-512148 (Dapagliflozin) in Asian Patients With Type 2 Diabetes Who Are Not Well Controlled on Metformin Alone

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ClinicalTrials.gov Identifier: NCT01095666
Recruitment Status : Completed
First Posted : March 30, 2010
Results First Posted : September 11, 2017
Last Update Posted : September 11, 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
Drug: Pioglitazone
Enrollment 1484
Recruitment Details Of 1484 patients enrolled, 554 completed a qualification period. Of these 554 patients, 444 were randomized and received treatment. Of these 444 participants, 409 completed the double-blind treatment period
Pre-assignment Details  
Arm/Group Title Placebo + Metformin Dapagliflozin 5 mg + Metformin Dapagliflozin 10 mg + Metformin
Hide Arm/Group Description [Not Specified] [Not Specified] [Not Specified]
Period Title: Overall Study
Started 145 147 152
Completed 128 136 145
Not Completed 17 11 7
Reason Not Completed
Lack of Efficacy             0             0             1
Adverse Event             2             1             3
Lost to Follow-up             2             2             0
Withdrawal by Subject             6             6             1
Non-compliance, not met criteria etc.             7             2             2
Arm/Group Title Placebo + Metformin Dapagliflozin 5 mg + Metformin Dapagliflozin 10 mg + Metformin Total
Hide Arm/Group Description [Not Specified] [Not Specified] [Not Specified] Total of all reporting groups
Overall Number of Baseline Participants 145 147 152 444
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 145 participants 147 participants 152 participants 444 participants
53.5  (9.20) 53.1  (9.09) 54.6  (9.54) 53.8  (9.29)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 145 participants 147 participants 152 participants 444 participants
Yonger than 65 years 129 132 126 387
65 to younger than 75 years 14 13 25 52
75 years and older 2 2 1 5
Sex/Gender, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 145 participants 147 participants 152 participants 444 participants
Male 86 67 88 241
Female 59 80 64 203
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 145 participants 147 participants 152 participants 444 participants
Asian Indian 10 11 13 34
Chinese 126 127 129 382
Korean 9 9 10 28
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 + Metformin Dapagliflozin 5 mg + Metformin Dapagliflozin 10 mg + Metformin
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 139 146 149
Mean (Standard Error)
Unit of Measure: % of hemoglobin
-0.23  (0.0622) -0.82  (0.0607) -0.85  (0.0601)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Metformin, Dapagliflozin 5 mg + Metformin
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 -0.59
Confidence Interval (2-Sided) 95%
-0.76 to -0.42
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0869
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo + Metformin, Dapagliflozin 10 mg + Metformin
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 -0.62
Confidence Interval (2-Sided) 95%
-0.79 to -0.45
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0865
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 + Metformin Dapagliflozin 5 mg + Metformin Dapagliflozin 10 mg + Metformin
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 140 146 151
Mean (Standard Error)
Unit of Measure: mg/dL
0.5  (2.357) -21.6  (2.308) -26.6  (2.269)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Metformin, Dapagliflozin 5 mg + Metformin
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 -22.1
Confidence Interval (2-Sided) 95%
-28.6 to -15.6
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.299
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo + Metformin, Dapagliflozin 10 mg + Metformin
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 -27.1
Confidence Interval (2-Sided) 95%
-33.5 to -20.7
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.271
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Adjusted Mean Change From Baseline in 2-hour Post Meal Glucose (PMG) (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 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. PMG 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 PMG values at baseline and Week 24 (LOCF)
Arm/Group Title Placebo + Metformin Dapagliflozin 5 mg + Metformin Dapagliflozin 10 mg + Metformin
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 117 117 124
Mean (Standard Error)
Unit of Measure: mg/dL
-15.5  (4.1548) -57.8  (4.1547) -64.6  (4.0357)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Metformin, Dapagliflozin 5 mg + Metformin
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 -42.3
Confidence Interval (2-Sided) 95%
-53.84 to -30.73
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.8758
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo + Metformin, Dapagliflozin 10 mg + Metformin
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 -49.1
Confidence Interval (2-Sided) 95%
-60.53 to -37.74
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.7921
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 + Metformin Dapagliflozin 5 mg + Metformin Dapagliflozin 10 mg + Metformin
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 141 147 151
Mean (Standard Error)
Unit of Measure: kg
-0.74  (0.1975) -1.84  (0.1935) -2.56  (0.1909)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Metformin, Dapagliflozin 5 mg + Metformin
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 -1.10
Confidence Interval (2-Sided) 95%
-1.65 to -0.56
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.2765
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo + Metformin, Dapagliflozin 10 mg + Metformin
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 -1.82
Confidence Interval (2-Sided) 95%
-2.36 to -1.28
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.2747
Estimation Comments [Not Specified]
5.Secondary Outcome
Title 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. 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. Percentage of participants were estimated by modified logistic regression model, adjusted for baseline HbA1c.
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 Week 24 (LOCF)
Arm/Group Title Placebo + Metformin Dapagliflozin 5 mg + Metformin Dapagliflozin 10 mg + Metformin
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 139 146 149
Measure Type: Number
Unit of Measure: Percentage of Participants
17.5 32.9 33.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Metformin, Dapagliflozin 5 mg + Metformin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0010
Comments Secondary endpoints were tested following a sequential testing procedure at alpha=0.05.
Method Modified logistic regression
Comments Modified logistic regression model, adjusted for baseline HbA1c
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 15.4
Confidence Interval (2-Sided) 95%
6.2 to 24.7
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.702
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo + Metformin, Dapagliflozin 10 mg + Metformin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0007
Comments Secondary endpoints were tested following a sequential testing procedure at alpha=0.05.
Method Modified logistic regression
Comments Modified logistic regression model, adjusted for baseline HbA1c
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 15.5
Confidence Interval (2-Sided) 95%
6.5 to 24.5
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.594
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 + Metformin Dapagliflozin 5 mg + Metformin Dapagliflozin 10 mg + Metformin
Hide Arm/Group Description [Not Specified] [Not Specified] [Not Specified]
All-Cause Mortality
Placebo + Metformin Dapagliflozin 5 mg + Metformin Dapagliflozin 10 mg + Metformin
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo + Metformin Dapagliflozin 5 mg + Metformin Dapagliflozin 10 mg + Metformin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/145 (4.14%)      3/147 (2.04%)      3/152 (1.97%)    
Cardiac disorders       
ANGINA UNSTABLE  1  1/145 (0.69%)  1 0/147 (0.00%)  0 0/152 (0.00%)  0
Congenital, familial and genetic disorders       
MYOCARDIAL BRIDGING  1  1/145 (0.69%)  1 0/147 (0.00%)  0 0/152 (0.00%)  0
Gastrointestinal disorders       
ABDOMINAL HERNIA  1  1/145 (0.69%)  1 0/147 (0.00%)  0 0/152 (0.00%)  0
Infections and infestations       
PNEUMONIA  1  1/145 (0.69%)  1 0/147 (0.00%)  0 0/152 (0.00%)  0
Injury, poisoning and procedural complications       
ANKLE FRACTURE  1  0/145 (0.00%)  0 0/147 (0.00%)  0 1/152 (0.66%)  1
LOWER LIMB FRACTURE  1  0/145 (0.00%)  0 0/147 (0.00%)  0 1/152 (0.66%)  1
JOINT INJURY  1  1/145 (0.69%)  1 0/147 (0.00%)  0 0/152 (0.00%)  0
Musculoskeletal and connective tissue disorders       
INTERVERTEBRAL DISC PROTRUSION  1  0/145 (0.00%)  0 1/147 (0.68%)  1 0/152 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
UTERINE LEIOMYOMA  1  0/145 (0.00%)  0 0/147 (0.00%)  0 1/152 (0.66%)  1
INFLAMMATORY PSEUDOTUMOUR  1  0/145 (0.00%)  0 1/147 (0.68%)  1 0/152 (0.00%)  0
SQUAMOUS CELL CARCINOMA  1  1/145 (0.69%)  1 0/147 (0.00%)  0 0/152 (0.00%)  0
LEIOMYOMA  1  0/145 (0.00%)  0 1/147 (0.68%)  1 0/152 (0.00%)  0
Reproductive system and breast disorders       
BENIGN PROSTATIC HYPERPLASIA  1  1/145 (0.69%)  1 0/147 (0.00%)  0 0/152 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
ASTHMA  1  1/145 (0.69%)  1 0/147 (0.00%)  0 0/152 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA Version: 16.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo + Metformin Dapagliflozin 5 mg + Metformin Dapagliflozin 10 mg + Metformin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   34/145 (23.45%)      43/147 (29.25%)      42/152 (27.63%)    
Infections and infestations       
URINARY TRACT INFECTION  1  7/145 (4.83%)  8 6/147 (4.08%)  6 10/152 (6.58%)  15
NASOPHARYNGITIS  1  5/145 (3.45%)  5 9/147 (6.12%)  9 7/152 (4.61%)  7
UPPER RESPIRATORY TRACT INFECTION  1  3/145 (2.07%)  3 14/147 (9.52%)  16 6/152 (3.95%)  6
Metabolism and nutrition disorders       
HYPERLIPIDAEMIA  1  16/145 (11.03%)  17 18/147 (12.24%)  18 18/152 (11.84%)  19
HYPERURICAEMIA  1  8/145 (5.52%)  12 6/147 (4.08%)  7 3/152 (1.97%)  3
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA Version: 16.0
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: NCT01095666     History of Changes
Other Study ID Numbers: MB102-055
First Submitted: March 26, 2010
First Posted: March 30, 2010
Results First Submitted: October 3, 2016
Results First Posted: September 11, 2017
Last Update Posted: September 11, 2017