Evaluation of Safety and Efficacy of Dapagliflozin in Subjects With Type 2 Diabetes Who Have Inadequate Glycaemic Control on Background Combination of Metformin and Sulfonylurea

This study has been completed.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01392677
First received: July 11, 2011
Last updated: February 11, 2014
Last verified: February 2014
Results First Received: November 5, 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
High HbA1c Level
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: 24 Oct 2011. Last participant completed 24 week period: 07 Jan 2013. 311 participants were enrolled, 219 were randomized in 45 centers in 5 European countries and in North America. Men and women aged >= 18 years with inadequate glycemic control (HbA1c 7.0% to 10.5% prior to randomization).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
During enrollment, diet and life-style advice was given to participants and was reinforced during a placebo lead-in period. Dose of anti-hyperglycemic combination therapy of metformin >= 1500 mg/day and maximum tolerated dose which must be at least half the maximum dose of sulfonylurea for at least 8 weeks prior to enrollment were to remain stable.

Reporting Groups
  Description
Placebo Plus Metformin Plus Sulfonylurea Placebo once daily plus background combination of metformin and sulfonylurea
Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea Dapagliflozin 10mg once daily plus background combination of metformin and sulfonylurea

Participant Flow:   Overall Study
    Placebo Plus Metformin Plus Sulfonylurea     Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea  
STARTED     109     109  
COMPLETED     101     101  
NOT COMPLETED     8     8  
Adverse Event                 3                 1  
Withdrawal by Subject                 0                 2  
Incorrect enrollment                 2                 3  
Other reason                 3                 2  



  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 study medication during the 24-week short-term double blind treatment period who have a non-missing baseline value and at least one post-baseline value for at least one efficacy variable to be analyzed at week 24.

Reporting Groups
  Description
Placebo Plus Metformin Plus Sulfonylurea Placebo once daily plus background combination of metformin and sulfonylurea
Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea Dapagliflozin 10mg once daily plus background combination of metformin and sulfonylurea
Total Total of all reporting groups

Baseline Measures
    Placebo Plus Metformin Plus Sulfonylurea     Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea     Total  
Number of Participants  
[units: participants]
  108     108     216  
Age  
[units: Years]
Mean ± Standard Deviation
  60.9  ± 9.24     61.1  ± 9.65     61.0  ± 9.42  
Gender  
[units: Participants]
     
Female     48     62     110  
Male     60     46     106  
Race/Ethnicity, Customized  
[units: Participants]
     
White     102     104     206  
Black/African American     1     0     1  
Asian     4     3     7  
Other     1     1     2  
Body Weight  
[units: kg]
Mean ± Standard Deviation
  90.07  ± 16.175     88.57  ± 17.584     89.32  ± 16.872  
Body Mass Index  
[units: kg/m^2]
Mean ± Standard Deviation
  32.02  ± 4.581     31.93  ± 4.840     31.97  ± 4.702  
Glycosylated hemoglobin A1c (HbA1c)  
[units: Percent]
Mean ± Standard Deviation
  8.24  ± 0.865     8.08  ± 0.912     8.16  ± 0.890  
Fasting Plasma Glucose  
[units: mg/dL]
Mean ± Standard Deviation
  180.2  ± 43.13     167.4  ± 43.32     173.8  ± 43.61  
Fasting C-Peptide  
[units: ng/mL]
Mean ± Standard Deviation
  2.5  ± 0.98     2.5  ± 1.06     2.5  ± 1.02  



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

2.  Secondary:   Adjusted Mean Change From Baseline in FPG   [ Time Frame: Baseline to week 24 ]

3.  Secondary:   Adjusted Mean Change From Baseline in Total Body Weight   [ Time Frame: Baseline to week 24 ]

4.  Secondary:   Proportion of Participants With HbA1c Value < 7.0% at Week 24 (LOCF)   [ Time Frame: Baseline to week 24 ]

5.  Secondary:   Adjusted Mean Change From Baseline in Seated Systolic Blood Pressure   [ Time Frame: Baseline to week 8 ]


  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
For participants who did not complete 8 and/or 24 weeks, respectively, last observation carried forward (LOCF) was used for analyses of secondary endpoints. All endpoints were evaluated by excluding data after rescue.


  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: Eva Johnsson
Organization: AstraZeneca
e-mail: ClinicalTrialTransparency@astrazeneca.com


No publications provided


Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01392677     History of Changes
Other Study ID Numbers: D1693C00005
Study First Received: July 11, 2011
Results First Received: November 5, 2013
Last Updated: February 11, 2014
Health Authority: Canada: Health Canada
Czech Republic: State Institute for Drug Control
Germany: Federal Institute for Drugs and Medical Devices
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Slovakia: State Institute for Drug Control
Spain: Comité Ético de Investigación Clínica
Spain: Spanish Agency of Medicines