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

This study has been completed.
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00528879
First received: September 11, 2007
Last updated: May 13, 2014
Last verified: April 2014
Results First Received: February 6, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Type 2 Diabetes
Interventions: Drug: Dapagliflozin
Drug: Placebo
Drug: Metformin

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Of 915 participants enrolled, 562 completed a qualification period. Of these 562 participants, 546 were randomized and received treatment and 16 were excluded due to adverse events (1), no longer meeting study criteria (7), poor compliance or noncompliance (3), withdrawn consent (4), and lost to follow-up (1).

Reporting Groups
  Description
Placebo + Metformin Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
Dapagliflozin, 2.5 mg + Metformin Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
Dapagliflozin, 5 mg + Metformin Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
Dapagliflozin, 10 mg + Metformin Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks

Participant Flow for 2 periods

Period 1:   Short-term Period (Day 1 to Week 24)
    Placebo + Metformin     Dapagliflozin, 2.5 mg + Metformin     Dapagliflozin, 5 mg + Metformin     Dapagliflozin, 10 mg + Metformin  
STARTED     137     137     137     135  
Completed the Period     119     121     122     121  
COMPLETED     115 [1]   120 [1]   122 [1]   119 [1]
NOT COMPLETED     22     17     15     16  
Lack of Efficacy                 3                 0                 1                 0  
Adverse Event                 4                 4                 2                 4  
Withdrawal by Subject                 7                 5                 5                 3  
Lost to Follow-up                 5                 4                 4                 5  
Poor compliance/noncompliance                 0                 0                 2                 0  
No longer meets study criteria                 2                 3                 0                 2  
Administrative reason by author                 1                 1                 0                 1  
Not specified                 0                 0                 1                 1  
[1] Completed=entered Long-term Period

Period 2:   Long-term Period (Weeks 24 to 102)
    Placebo + Metformin     Dapagliflozin, 2.5 mg + Metformin     Dapagliflozin, 5 mg + Metformin     Dapagliflozin, 10 mg + Metformin  
STARTED     115     120     122     119  
COMPLETED     73     82     89     95  
NOT COMPLETED     42     38     33     24  
Lack of Efficacy                 27                 16                 17                 9  
Adverse Event                 5                 4                 3                 2  
Withdrawal by Subject                 4                 6                 8                 4  
Death                 0                 1                 0                 0  
Lost to Follow-up                 4                 5                 3                 7  
Poor compliance/noncompliance                 0                 5                 1                 2  
Pregnancy                 1                 0                 0                 0  
No longer meets study criteria                 1                 1                 1                 0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants who received at least 1 dose of study medication

Reporting Groups
  Description
Placebo + Metformin Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
Dapagliflozin, 2.5 mg + Metformin Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
Dapagliflozin, 5 mg + Metformin Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
Dapagliflozin, 10 mg + Metformin Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
Total Total of all reporting groups

Baseline Measures
    Placebo + Metformin     Dapagliflozin, 2.5 mg + Metformin     Dapagliflozin, 5 mg + Metformin     Dapagliflozin, 10 mg + Metformin     Total  
Number of Participants  
[units: participants]
  137     137     137     135     546  
Age  
[units: Years]
Mean ( Full Range )
  53.7  
  ( 30 to 74 )  
  55.0  
  ( 30 to 76 )  
  54.3  
  ( 33 to 75 )  
  52.7  
  ( 29 to 76 )  
  53.9  
  ( 29 to 76 )  
Age, Customized  
[units: Participants]
         
Younger than 65 years     114     116     119     118     467  
65 to younger than 75 years     23     19     17     16     75  
75 years and older     0     2     1     1     4  
Gender  
[units: Participants]
         
Female     61     67     68     58     254  
Male     76     70     69     77     292  
Race/Ethnicity, Customized  
[units: Participants]
         
White     124     117     118     121     480  
Black/African American     2     5     6     4     17  
Asian     3     3     4     1     11  
Native Hawaiian/Other Pacific Islander     0     0     1     0     1  
American Indian/Alaskan Native     1     2     2     4     9  
Other     7     10     6     5     28  
Female Age  
[units: Participants]
         
50 Years and younger     25     18     22     22     87  
Older than 50 years     36     49     46     36     167  
Body Mass Index  
[units: Participants]
         
<25 kg/m^2     9     4     12     12     37  
≥25 kg/m^2     128     133     125     123     509  
≥27 kg/m^2     115     120     111     106     452  
≥30 kg/m^2     79     77     81     75     312  



  Outcome Measures
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1.  Primary:   Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24 (Last Observation Carried Forward [LOCF])   [ Time Frame: From Baseline to Week 24 ]

2.  Secondary:   Adjusted Mean Change From Baseline in Fasting Plasma Glucose at Week 24 (Last Observation Carried Forward [LOCF])   [ Time Frame: From Baseline to Week 24 ]

3.  Secondary:   Adjusted Mean Change From Baseline in Total Body Weight at Week 24 (Last Observation Carried Forward [LOCF])   [ Time Frame: From Baseline to Week 24 ]

4.  Secondary:   Percentage of Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 24 (Last Observation Carried Forward [LOCF])   [ Time Frame: From Baseline to Week 24 ]

5.  Secondary:   Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) in Participants With Baseline HbA1c ≥9.0% at Week 24 (Last Observation Carried Forward [LOCF])   [ Time Frame: From Baseline to Week 24 ]

6.  Secondary:   Adjusted Mean Change From Baseline in Total Body Weight at Week 24 in Participants With Baseline Body Mass Index (BMI) ≥27 kg/m^2 (Last Observation Carried Forward [LOCF])   [ Time Frame: From Baseline to Week 24 ]

7.  Secondary:   Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) in Participants With Baseline Body Mass Index (BMI) ≥27 kg/m^2 at Week 24 (Last Observation Carried Forward [LOCF])   [ Time Frame: From Baseline to Week 24 ]

8.  Secondary:   Adjusted Mean Change From Baseline in Fasting Plasma Glucose at Week 1 (Last Observation Carried Forward [LOCF])   [ Time Frame: From Baseline to Week 1 ]

9.  Secondary:   Adjusted Percentage of Participants Achieving Hemoglobin A1c (HbA1C) ≤6.5% at Week 24 (Last Observation Carried Forward [LOCF])   [ Time Frame: From Baseline to Week 24 ]

10.  Other Pre-specified:   Number of Participants With Adverse Events (AEs), Hypoglycemia Events, Related AEs, Death as Outcome, Serious AEs (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs Leading to Discontinuation, and Hypoglycemia Events Leading to Discontinuation   [ Time Frame: From Baseline to end of Long-term Period (Week 102) ]

11.  Other Pre-specified:   Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality   [ Time Frame: Day 1 to Week 102 ]

12.  Other Pre-specified:   Number of Participants With Changes in Baseline in Electrocardiogram Findings at Week 102 (Last Observation Carried Forward [LOCF])   [ Time Frame: Baseline to Week 102 ]

13.  Other Pre-specified:   Mean Changes From Baseline in Seated Systolic Blood Pressure   [ Time Frame: From Baseline to Week 102 ]

14.  Other Pre-specified:   Mean Changes From Baseline in Seated Diastolic Blood Pressure   [ Time Frame: From Baseline to Week 102 ]

15.  Other Pre-specified:   Number of Participants With Orthostatic Hypotension   [ Time Frame: From Baseline to Week 102 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
e-mail: Clinical.Trials@bms.com


No publications provided by Bristol-Myers Squibb

Publications automatically indexed to this study:

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00528879     History of Changes
Other Study ID Numbers: MB102-014 LT
Study First Received: September 11, 2007
Results First Received: February 6, 2014
Last Updated: May 13, 2014
Health Authority: United States: Food and Drug Administration
Argentina: Administración Nacional de Medicamentos Alimentos y Tecnología Médica
Brazil: Ministério da Saúde and Agência Nacional de Vigilância Sanitária (National Health Surveillance Agency)
Canada: Health Canada
Mexico: Federal Commission for Protection Against Health Risks
Russia: Ministry of Public Health and Social Development of Russian Federation and Ethic Committee of Federal Supervision Service for Public Health and Social Affairs