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:
AstraZeneca
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01137474
First received: June 3, 2010
Last updated: April 1, 2014
Last verified: April 2014
Results First Received: February 7, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator);   Primary Purpose: Treatment
Condition: Type 2 Diabetes
Interventions: Drug: Dapagliflozin
Drug: Placebo-matching dapagliflozin
Drug: Oral antidiabetic agent
Drug: Angiotensin-converting enzyme (ACE) inhibitor or angiotensin-receptor blocker (ARB)
Drug: With or without insulin

  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 for 2 periods

Period 1:   Day 1 to Week 12 (Double-blind Period)
    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  

Period 2:   Follow-up (1 Week Post Last Dose)
    Placebo     Dapagliflozin, 2.5 mg (Randomized Before Protocol Amendment 8)     Dapagliflozin, 5 mg (Randomized Before Protocol Amendment 8)     Dapagliflozin, 10 mg  
STARTED     288 [1]   155 [1]   158     284 [2]
COMPLETED     265     153     157     266  
NOT COMPLETED     23     2     1     18  
Withdrawal by Subject                 9                 0                 0                 10  
Lost to Follow-up                 5                 0                 0                 2  
Administrative reason by sponsor                 1                 0                 0                 2  
Not specified                 8                 2                 1                 4  
[1] Includes 1 participant who discontinued prematurely in Period 1 and returned for follow-up
[2] Includes 3 participants who discontinued prematurely in Period 1 and returned for follow-up



  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 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 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  
Number of Participants  
[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]
         
Female     140     76     76     123     415  
Male     171     90     89     179     529  
Ethnicity (NIH/OMB) [1]
[units: Participants]
         
Hispanic or Latino     81     28     23     87     219  
Not Hispanic or Latino     43     16     20     31     110  
Unknown or Not Reported     187     122     122     184     615  
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 and greater     283     146     147     268     844  
27 kg/m^2 and greater     240     123     129     238     730  
30 kg/m^2 and greater     152     79     84     173     488  
[1] Reported only for US participants



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Adjusted Mean Change From Baseline in Seated Systolic Blood Pressure (BP) at Week 12   [ Time Frame: From Baseline to Week 12 ]

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 ]

7.  Other Pre-specified:   Number of Participants With Adverse Events (AEs), Hypoglycemic Events, Related AEs, Death as Outcome, Serious Adverse Events (SAEs), Related SAEs, Discontinuations Due to SAEs, Discontinuations Due to AEs, and Discontinuations Due to Hypoglycemic Events   [ Time Frame: Day 1 of treatment to last dose plus 4 days for AEs and hypoglycemic events and plus 30 days for SAEs ]

8.  Other Pre-specified:   Number of Participants With Clinical Laboratory Results Meeting Criteria for Marked Abnormality   [ Time Frame: Day 1 of treatment to last dose, plus 4 days ]

9.  Other Pre-specified:   Changes From Baseline in Electrocardiogram (ECG) Findings at Week 12   [ Time Frame: From Baseline to Week 12 ]

10.  Other Pre-specified:   Changes From Baseline in Supine and Standing Systolic and Diastolic Blood Pressure (BP) at Week 12   [ Time Frame: From Baseline to Week 12 ]
  Hide Outcome Measure 10

Measure Type Other Pre-specified
Measure Title Changes From Baseline in Supine and Standing Systolic and Diastolic Blood Pressure (BP) at Week 12
Measure Description Supine BP was measured prior to standing BP. The patient was to rest in the supine position for at least 5 minutes prior to measurement of BP. Supine BP was determined from 3 replicate measurements obtained at least 1 minute apart. The average BP was determined from these 3 replicate measurements. The patient then stood for 2 to 3 minutes. After this time, BP was measured with the arm supported at the antecubital fossa at heart level.
Time Frame From Baseline to Week 12  
Safety Issue Yes  

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 were included. n=number of patients with nonmissing Week 12 values

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

Measured Values
    Placebo     Dapagliflozin, 10 mg  
Number of Participants Analyzed  
[units: participants]
  311     302  
Changes From Baseline in Supine and Standing Systolic and Diastolic Blood Pressure (BP) at Week 12  
[units: mm Hg]
Mean ± Standard Deviation
   
Supine systolic BP (n=276, 275)     -5.52  ± 11.042     -9.26  ± 12.049  
Standing systolic BP (n=277, 276)     -6.35  ± 12.354     -9.64  ± 12.601  
Supine diastolic BP (n=276, 275)     -3.70  ± 6.787     -5.11  ± 8.026  
Standing diastolic BP (n=277, 276)     -3.64  ± 7.124     -5.25  ± 7.376  

No statistical analysis provided for Changes From Baseline in Supine and Standing Systolic and Diastolic Blood Pressure (BP) at Week 12



11.  Other Pre-specified:   Changes From Baseline in Supine and Standing Heart Rate (HR) at Week 12   [ Time Frame: From Baseline to Week 12 ]

12.  Other Pre-specified:   Changes From Baseline in 24-Hour Ambulatory Heart Rate at Week 12   [ Time Frame: From Baseline to Week 12 ]

13.  Other Pre-specified:   Number of Participants With Elevated Results of Liver Laboratory Tests   [ Time Frame: Day 1 of double-blind treatment to last double-blind dose, plus 30 days ]


  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: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
e-mail: Clinical.Trials@bms.com


No publications provided


Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01137474     History of Changes
Other Study ID Numbers: MB102-073 ST, 2010-019797-32
Study First Received: June 3, 2010
Results First Received: February 7, 2014
Last Updated: April 1, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration
Canada: Health Canada
Mexico: Secretaria de Salud
Germany: Federal Institute for Drugs and Medical Devices
Australia: Department of Health and Ageing Therapeutic Goods Administration
Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Hungary: National Institute of Pharmacy
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: Ministry of Health of the Russian Federation