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A Study of BMS-512148 (Dapagliflozin) in Patients With Type 2 Diabetes and Inadequately Controlled Hypertension on an Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker

This study has been completed.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01137474
First received: June 3, 2010
Last updated: December 2, 2016
Last verified: November 2016
Results First Received: February 7, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition: Type 2 Diabetes
Interventions: Drug: Dapagliflozin
Drug: Placebo-matching dapagliflozin

  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

This study was originally designed with 2 additional double-blind treatment arms, dapagliflozin 2.5 and

5 mg, but randomization of new patients into these arms stopped with implementation of Protocol Amendment 8

on 1-11-11. Patients randomized to dapagliflozin 2.5 or 5 mg remained on their blinded medication until study completion.


Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Of 2996 participants enrolled, 944 were randomized and received double-blind treatment.

Reporting Groups
  Description
Placebo Participants with type 2 diabetes and inadequate glycemic and hypertension control while taking an oral antidiabetic drug (OAD) with or without insulin and an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB), received dapagliflozin-matching placebo daily with a morning meal.
Dapagliflozin, 2.5 mg (Randomized Before Protocol Amendment 8) Participants with type 2 diabetes and inadequate glycemic and hypertension control while taking an OAD with or without insulin and an ACE inhibitor or ARB, received dapagliflozin, 2.5 mg, daily with a morning meal.
Dapagliflozin, 5 mg (Randomized Before Protocol Amendment 8) Participants with type 2 diabetes and inadequate glycemic and hypertension control while taking an OAD with or without insulin and an ACE inhibitor or ARB, received dapagliflozin, 5 mg, daily with a morning meal.
Dapagliflozin 10 mg Participants with type 2 diabetes and inadequate glycemic and hypertension control while taking an OAD with or without insulin and an ACE inhibitor or ARB, received dapagliflozin, 10 mg, daily with a morning meal.

Participant Flow:   Overall Study
    Placebo   Dapagliflozin, 2.5 mg (Randomized Before Protocol Amendment 8)   Dapagliflozin, 5 mg (Randomized Before Protocol Amendment 8)   Dapagliflozin 10 mg
STARTED   311   166   165   302 
Received Treatment   311   166   165   302 
COMPLETED   287   154   158   281 
NOT COMPLETED   24   12   7   21 
Adverse Event                3                5                1                3 
Withdrawal by Subject                7                2                6                9 
No longer met study criteria                6                1                0                5 
Lost to Follow-up                5                1                0                2 
Lack of Efficacy                0                0                0                2 
Not specified                3                1                0                0 
Pregnancy                0                1                0                0 
Administrative reason by sponsor                0                1                0                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 a least 1 dose of double-blind study medication

Reporting Groups
  Description
Placebo Participants with type 2 diabetes and inadequate glycemic and hypertension control while taking an oral antidiabetic drug (OAD) with or without insulin and an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB), received dapagliflozin-matching placebo daily with a morning meal.
Dapagliflozin, 2.5 mg (Randomized Before Protocol Amendment 8) Participants with type 2 diabetes and inadequate glycemic control while taking an OAD with or without insulin and an ACE inhibitor or ARB, received dapagliflozin, 2.5 mg, daily with a morning meal.
Dapagliflozin, 5 mg (Randomized Before Protocol Amendment 8) Participants with type 2 diabetes and inadequate glycemic control while taking an OAD with or without insulin and an ACE inhibitor or ARB, received dapagliflozin, 5 mg, daily with a morning meal.
Dapagliflozin 10 mg Participants with type 2 diabetes and inadequate glycemic and hypertension control while taking an OAD with or without insulin and an ACE inhibitor or ARB, received dapagliflozin, 10 mg, daily with a morning meal.
Total Total of all reporting groups

Baseline Measures
   Placebo   Dapagliflozin, 2.5 mg (Randomized Before Protocol Amendment 8)   Dapagliflozin, 5 mg (Randomized Before Protocol Amendment 8)   Dapagliflozin 10 mg   Total 
Overall Participants Analyzed 
[Units: Participants]
 311   166   165   302   944 
Age, Customized 
[Units: Participants]
         
Younger than 65 years   259   141   142   260   802 
65 years and older to younger than 75 years   46   25   21   42   134 
75 years and older   6   0   2   0   8 
Gender 
[Units: Participants]
Count of Participants
         
Female      140  45.0%      76  45.8%      76  46.1%      123  40.7%      415  44.0% 
Male      171  55.0%      90  54.2%      89  53.9%      179  59.3%      529  56.0% 
Race/Ethnicity, Customized 
[Units: Participants]
         
White   241   105   108   239   693 
Black or African American   14   11   8   12   45 
Asian   54   49   49   49   201 
Other   2   1   0   2   5 
Body Mass Index 
[Units: Participants]
         
Less than 25 kg/m^2   28   20   18   34   100 
25 kg/m^2 to 30 kg/m^2   131   67   63   95   356 
30 kg/m^2 and greater   152   79   84   173   488 


  Outcome Measures
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1.  Primary:   Adjusted Mean Change From Baseline in Seated Systolic Blood Pressure (BP) at Week 12   [ Time Frame: From Baseline to Week 12 ]
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Measure Type Primary
Measure Title Adjusted Mean Change From Baseline in Seated Systolic Blood Pressure (BP) at Week 12
Measure Description Seated BP was to be measured at every visit. Data after rescue medication was excluded. The patient first rested for at least 10 minutes in the seated position. Seated blood BP was determined from the mean of 3 replicated measurements obtained at least 1 minute apart. However, if the 3 consecutive seated BP readings were not within 8 mm Hg of each other, an additional 2 BP readings were to be obtained (total=5) and incorporated into the calculated mean for systolic BP and diastolic BP. For the initial BP recording, BP was measured in both arms. If the BP was higher in 1 arm, that arm was used for BP measurement. If there was no difference in BP measurements between arms, the dominant arm was used for all future BP measurements. All randomized participants who received at least 1 dose of study drug and who had nonmissing baseline and at least 1 postbaseline value during the double-blind treatment period were used for analysis. SD=standard deviation.
Time Frame From Baseline to Week 12  

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.
This study originally had 2 additional arms-dapagliflozin 2.5 and 5 mg-but randomization to these arms stopped when Protocol Amendment 8 (1-11-11) was implemented. Because endpoints focused only on 10-mg and placebo data, only patients in these arms who received study drug and who had nonmissing baseline and Week 12 values were included.

Reporting Groups
  Description
Dapagliflozin 10 mg Participants with type 2 diabetes and inadequate glycemic and hypertension control while taking an OAD with or without insulin and an ACE inhibitor or ARB, received dapagliflozin, 10 mg, daily with a morning meal.
Placebo Participants with type 2 diabetes and inadequate glycemic and hypertension control while taking an oral antidiabetic drug (OAD) with or without insulin and an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB), received dapagliflozin-matching placebo daily with a morning meal.

Measured Values
   Dapagliflozin 10 mg   Placebo 
Participants Analyzed 
[Units: Participants]
 280   279 
Adjusted Mean Change From Baseline in Seated Systolic Blood Pressure (BP) at Week 12 
[Units: Mm Hg]
Mean (Standard Error)
 -10.40  (0.8822)   -7.34  (0.8812) 


Statistical Analysis 1 for Adjusted Mean Change From Baseline in Seated Systolic Blood Pressure (BP) at Week 12
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Longitudinal repeated measures analysis
P Value [4] 0.0010
Mean Difference (Final Values) [5] -3.05
95% Confidence Interval -4.87 to -1.24
Standard Error of the mean (0.9251)
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from baseline to week 12 calculated using a longitudinal repeated measures analysis using direct likelihood with fixed categorical effects of treatment, week, treatment-by-week interaction, and randomization strata and continuous fixed covariates of baseline value and baseline value by week interaction. Data after rescue were not included in the analysis. With 253 patients per group, there is >80% power to detect a difference of 3.5 mm Hg at alpha=0.05, assuming a common SD of 14 mm Hg.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  Only Week 12 data are presented; data from all weeks in double-blind period were included in the longitudinal repeated measures model.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Endpoint tested following a sequential testing procedure at two-sided alpha=0.05 to control the family-wise Type I error rate related to primary and secondary efficacy endpoints. Test performed since previous tests were significant.
[5] Other relevant estimation information:
  No text entered.



2.  Primary:   Adjusted Mean Change From Baseline in Hemoglobin (HbA1c) at Week 12   [ Time Frame: From Baseline to Week 12 ]

3.  Secondary:   Adjusted Mean Change From Baseline in 24-Hour Ambulatory Systolic Blood Pressure at Week 12 (Last Observation Carried Forward)   [ Time Frame: From Baseline to Week 12 ]

4.  Secondary:   Adjusted Mean Change From Baseline in Seated Diastolic Blood Pressure at Week 12   [ Time Frame: From Baseline to Week 12 ]

5.  Secondary:   Adjusted Mean Change in 24-Hour Ambulatory Diastolic Blood Pressure at Week 12 (Last Observation Carried Forward [LOCF])   [ Time Frame: From Baseline to Week 12 ]

6.  Secondary:   Adjusted Mean Change From Baseline in Serum Uric Acid Levels at Week 12   [ Time Frame: From Baseline to Week 12 ]


  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
Study originally had 2 additional arms, dapagliflozin 2.5 and 5 mg, but enrolment stopped after Protocol Amendment 8 (1-11-11) implemented. Because endpoints focused on comparison of dapagliflozin 10 mg with placebo, only these arms were summarized.


  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: AstraZeneca
Organization: Clinical Trial Transparency
e-mail: ClinicalTrialTransparency@astrazeneca.com



Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01137474     History of Changes
Other Study ID Numbers: MB102-073 ST
2010-019797-32 ( EudraCT Number )
Study First Received: June 3, 2010
Results First Received: February 7, 2014
Last Updated: December 2, 2016