Efficacy and Safety in Patients With Type 2 Diabetes Mellitus and Cardiovascular Disease

This study has been completed.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01042977
First received: January 5, 2010
Last updated: December 18, 2013
Last verified: December 2013
Results First Received: January 21, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions: Type 2 Diabetes Mellitus
Cardiovascular Disease
Inadequate Glycaemic Control
Interventions: Drug: Dapagliflozin
Drug: Placebo

  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
First participant enrolled 15 Mar 2010, last part. last visit for 24-week period: 30 May 2011. 1489 part. enrolled, 964 randomized in USA, Canada, Australia, Chile, Argentina and 5 European countries (value presented in ‘Enrolment’ field). One add. part. treated but not randomized. Part. with T2DM and CVD who showed inadequate glycemic control.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
During a placebo lead-in period, participants were counselled on dietary and life-style modifications. Anti-diabetic therapy should be kept constant 4 weeks prior to enrolment. Participants eligible for the study were stratified according to age (<65 years or ≥65 years), insulin use and time from most recent qualifying CV event (>1 or ≤1 year).

Reporting Groups
  Description
Dapagliflozin Dapagliflozin 10 mg plus usual care
Placebo Placebo plus usual care

Participant Flow:   Overall Study
    Dapagliflozin     Placebo  
STARTED     482 [1]   483 [2]
COMPLETED     441     428  
NOT COMPLETED     41     55  
Adverse Event                 4                 12  
Death                 2                 1  
Withdrawal by Subject                 8                 16  
Lost to Follow-up                 0                 2  
Poor/non-compliance                 3                 4  
Subject no longer meets study criteria                 15                 13  
Incorrect enrollment                 6                 4  
Safety                 0                 2  
Administrative reason by sponsor                 0                 1  
Various                 3                 0  
[1] Of 482 part. 480 were included in full analysis set. Thereof, 1 part. treated but not randomized.
[2] Of the 483 participants only 482 were included in the full analysis set.



  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.
Full Analysis Set defined as all randomized participants (as randomized) who received at least one dose of double-blind study medication, who have a non-missing baseline value and at least one post-baseline efficacy value for at least one efficacy variable during double-blind treatment period.

Reporting Groups
  Description
Dapagliflozin Dapagliflozin 10 mg plus usual care
Placebo Placebo plus usual care
Total Total of all reporting groups

Baseline Measures
    Dapagliflozin     Placebo     Total  
Number of Participants  
[units: participants]
  480     482     962  
Age  
[units: Years]
Mean ± Standard Deviation
  63.9  ± 7.60     63.6  ± 7.02     63.8  ± 7.31  
Gender  
[units: Participants]
     
Female     159     159     318  
Male     321     323     644  
Race/Ethnicity, Customized  
[units: Participants]
     
White     454     449     903  
Black/African American     9     10     19  
Asian     6     7     13  
Other     11     16     27  
HbA1c  
[units: Percent]
Mean ± Standard Deviation
  8.04  ± 0.759     8.08  ± 0.795     8.06  ± 0.777  
Body weight  
[units: kg]
Mean ± Standard Deviation
  94.53  ± 17.804     93.23  ± 16.842     93.88  ± 17.332  
Systolic Blood Pressure  
[units: mmHg]
Mean ± Standard Deviation
  134.9  ± 14.53     134.6  ± 13.96     134.7  ± 14.24  
Number of participants with BMI >= 27 kg/m2 at baseline  
[units: Participants]
     
< 25 kg/m²     15     31     46  
>= 25 kg/m²     465     451     916  
>= 27 kg/m²     428     416     844  
>= 30 kg/m²     339     325     664  



  Outcome Measures
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1.  Primary:   Adjusted Mean Change in HbA1c Levels   [ Time Frame: Baseline to Week 24 ]

2.  Primary:   Proportion of Responders Meeting All Criteria of a 3-item Endpoint of Clinical Benefit   [ Time Frame: Baseline to Week 24 ]

3.  Secondary:   Adjusted Mean Percent Change in Body Weight   [ Time Frame: Baseline to Week 24 ]

4.  Secondary:   Proportion of Participants With a Reduction From Baseline of 5% or More in Body Weight in Participants With Baseline BMI ≥27 kg/m²   [ Time Frame: Baseline to Week 24 ]

5.  Secondary:   Adjusted Mean Change in Systolic Blood Pressure at Week 8 (LOCF)   [ Time Frame: Baseline to Week 8 ]

6.  Secondary:   Adjusted Mean Change in Seated Systolic Blood Pressure at Week 24 (LOCF)   [ Time Frame: Baseline to Week 24 ]

7.  Secondary:   Adjusted Mean Change in Seated Systolic Blood Pressure (SBP) at Week 8 (LOCF) in Participants With Baseline SBP>=130 mmHg   [ Time Frame: Baseline to Week 8 ]
  Hide Outcome Measure 7

Measure Type Secondary
Measure Title Adjusted Mean Change in Seated Systolic Blood Pressure (SBP) at Week 8 (LOCF) in Participants With Baseline SBP>=130 mmHg
Measure Description To compare the mean change in seated systolic blood pressure (SBP) in participants with baseline seated SBP ≥130 mmHg achieved with dapagliflozin versus placebo from baseline to week 8.
Time Frame Baseline to Week 8  
Safety Issue No  

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.
Full Analysis set, participants with baseline seated SBP ≥130 mmHg and Week 8 (LOCF) value

Reporting Groups
  Description
Dapagliflozin Dapagliflozin 10 mg plus usual care
Placebo Placebo plus usual care

Measured Values
    Dapagliflozin     Placebo  
Number of Participants Analyzed  
[units: participants]
  300     309  
Adjusted Mean Change in Seated Systolic Blood Pressure (SBP) at Week 8 (LOCF) in Participants With Baseline SBP>=130 mmHg  
[units: mmHg]
Least Squares Mean ( 95% Confidence Interval )
  -5.33  
  ( -7.02 to -3.64 )  
  -1.89  
  ( -3.58 to -0.20 )  


Statistical Analysis 1 for Adjusted Mean Change in Seated Systolic Blood Pressure (SBP) at Week 8 (LOCF) in Participants With Baseline SBP>=130 mmHg
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.0004
Mean Difference (Final Values) [4] -3.44
Standard Error of the mean ± 0.9746
95% Confidence Interval ( -5.35 to -1.53 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  H0: mean(treat) minus mean(placebo) = 0 versus the alternative HA: mean(treat) minus mean(placebo) =/= 0
[2] Other relevant method information, such as adjustments or degrees of freedom:
  with treatment group and stratum as effects and baseline value as covariate
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Significant at alpha=0.05 (2-sided). Primary and key secondary endpoints are tested following a hierarchical closed testing procedure
[4] Other relevant estimation information:
  with stratum = age-by-insulin use-by-time from most recent qualifying CV event




  Serious Adverse Events


  Other Adverse Events


  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.


Limitations and Caveats
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
For participants who did not complete 8 and/or 24 weeks, respectively, LOCF was used. For HbA1c: excluding data after glycemic rescue, Weight: including data after rescue, SBP: excluding data after anti-hypertensive rescue.  


Results Point of Contact:  
Name/Title: Eva Johnsson
Organization: AstraZeneca
e-mail: ClinicalTrialTransparency@astrazeneca.com


No publications provided


Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01042977     History of Changes
Other Study ID Numbers: D1690C00019
Study First Received: January 5, 2010
Results First Received: January 21, 2013
Last Updated: December 18, 2013
Health Authority: United States: Food and Drug Administration