Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

A Study of BMS-512148 (Dapagliflozin) in Patients With Type 2 Diabetes With Inadequately Controlled Hypertension on an ACEI or ARB and an Additional Antihypertensive Medication

This study has been completed.
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01195662
First received: September 3, 2010
Last updated: April 28, 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

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Recruitment: 29-Oct-2010 to 04-Oct-2012. Original study had 3 arms but 5 mg dapagliflozin arm was discontinued with Protocol Amendment 8 (implemented 01-Nov-2011) because totality of data in development program showed that once daily 10-mg dapagliflozin provides optimal efficacy with safety and tolerance. Study continued to enroll with 2 arms.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
2245 enrolled. 1213 completed enrollment;1032 not completed:1 adverse event (AE), 65 withdrew consent (WC), 7 lost to follow up (LTF), 2 administrative (admin), 934 criteria not met, 2 non-compliant, 21 other. Lead-In: 588 randomized; 625 not randomized: 6 AE, 69 WC, 13 LTF, 8 admin, 2 at request, 497 criteria not met, 11 non-compliant, 19 other.

Reporting Groups
  Description
Placebo Matching Dapagliflozin Placebo matching dapagliflozin: Tablets, Oral, 0 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
Dapagliflozin 10 mg Dapagliflozin: Tablets, Oral, 10 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
Dagagliflozin 5 mg (Arm Discontinued With Amendment 8)

Dapagliflozin: Tablets, Oral, 5 mg, once a day for up to12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.

This arm was discontinued with Amendment 8 to the protocol (implemented 1 November 2011) and the other 2 arms continued to enroll. This arm is not included in primary and secondary efficacy analysis.


Participant Flow for 2 periods

Period 1:   Double Blind Treatment Period
    Placebo Matching Dapagliflozin     Dapagliflozin 10 mg     Dagagliflozin 5 mg (Arm Discontinued With Amendment 8)  
STARTED     224     225     133  
COMPLETED     202     211     119  
NOT COMPLETED     22     14     14  
Adverse Event                 4                 1                 2  
Withdrawal by Subject                 6                 4                 4  
Lost to Follow-up                 3                 2                 3  
Administrative reason                 2                 1                 1  
Requested discontinue treatment                 1                 0                 1  
No Longer Meets Criteria                 1                 5                 2  
Lack of Efficacy                 2                 0                 0  
Non-specified                 3                 0                 0  
Missing disposition information                 0                 1                 1  

Period 2:   Follow-Up(Week 13/1 Week Post Last Dose)
    Placebo Matching Dapagliflozin     Dapagliflozin 10 mg     Dagagliflozin 5 mg (Arm Discontinued With Amendment 8)  
STARTED     203 [1]   209 [2]   120 [3]
COMPLETED     200     209     119  
NOT COMPLETED     3     0     1  
Withdrawal by Subject                 2                 0                 1  
non-specified                 1                 0                 0  
[1] 1 participant discontinued drug but remained in study and entered Follow-Up.
[2] 2 participants completed treatment period but chose not to enter follow up period.
[3] 1 participant discontinued drug but remained in the study and entered the follow up period.



  Baseline Characteristics
  Hide Baseline Characteristics

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.
Participants in Double-Blind Period who were randomized and treated with at least one dose of double-blind study medication.

Reporting Groups
  Description
Placebo Matching Dapagliflozin Placebo matching dapagliflozin: Tablets, Oral, 0 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
Dapagliflozin 10 mg Dapagliflozin: Tablets, Oral, 10 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
Dagagliflozin 5 mg (Arm Discontinued With Amendment 8) Dapagliflozin: Tablets, Oral, 5 mg, once daily, Up to 12 weeks. This arm discontinued with implementation of Amendment 8 to the protocol (1 November 2011). Study continued to enroll participants in other 2 arms post Amendment 8. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
Total Total of all reporting groups

Baseline Measures
    Placebo Matching Dapagliflozin     Dapagliflozin 10 mg     Dagagliflozin 5 mg (Arm Discontinued With Amendment 8)     Total  
Number of Participants  
[units: participants]
  224     225     133     582  
Age, Customized  
[units: participants]
       
Less than (<) 65 years     198     198     118     514  
Greater than, equal (>=) to 65 and < 75 years     25     23     14     62  
>= 75 years     1     4     1     6  
Gender  
[units: participants]
       
Female     95     107     52     254  
Male     129     118     81     328  
Race/Ethnicity, Customized [1]
[units: participants]
       
White     157     160     84     401  
Black or African American     17     19     9     45  
Asian     38     34     36     108  
Other Race     12     12     4     28  
Ethnicity Hispanic/Latino     41     47     21     109  
Ethnicity Not Hispanic/Latino     40     38     16     94  
Ethnicity Not Reported     143     140     96     379  
Body Mass Index (BMI) [2]
[units: participants]
       
< 25 kg/m^2     21     17     9     47  
>=25 kg/m^2     203     208     124     535  
>=27 kg/m^2     179     178     101     458  
>=30 kg/m^2     147     141     73     361  
Hypertension Medication [3]
[units: participants]
       
Thiazide or thiazide-like diuretics, no insulin     94     95     54     243  
Calcium channel and beta blockers, no insulin     114     112     79     305  
Thiazide or thiazide-like diuretics, insulin     5     6     0     11  
Calcium channel and beta blockers, insulin     11     12     0     23  
[1] Ethnicity was collected and summarized only for USA participants.
[2] BMI is measured by weight in kilograms (kg) divided by height in meters (m) squared (kg/m^2). Less than (<); Greater than, equal to (>=).
[3]

The following categories served as a randomization stratification factor:

category 1: thiazide or thiazide-like diuretics and no insulin category 2: calcium channel blockers, beta blockers, central alpha adrenergic agonist or alpha adrenergic blockers and no insulin category 3: thiazide or thiazide-like diuretics and insulin category 4: calcium channel blockers, beta blockers, central alpha adrenergic agonist or alpha adrenergic blockers and insulin




  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Adjusted Mean Change From Baseline in Seated Systolic Blood Pressure for 12 Week Double-Blind Treatment Period - Randomized Participants   [ Time Frame: Baseline to Week 12 ]

Measure Type Primary
Measure Title Adjusted Mean Change From Baseline in Seated Systolic Blood Pressure for 12 Week Double-Blind Treatment Period - Randomized Participants
Measure Description Systolic blood pressure (SBP) was measured in millimeters of mercury (mmHg) on Day -1, Day 1, Weeks 2, 4, 8, and 12 of the Double Blind Period. Blood pressure (BP) values were obtained after the participant was seated for quietly for 10 minutes; a mean of 3 replicate measurements was taken 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 obtained (total = 5) and incorporated into the calculated mean. BP was measured in both arms. If the BP was higher in one arm than the other, then this arm was used; if no difference, the participant’s dominant arm was used for all future BP measurements. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. Participants refrained from ingestion of caffeine, alcohol, or nicotine at least 10 hours prior to their visit and having their BP measured.
Time Frame Baseline to Week 12  
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.
All randomized participants who received double-blind medication and had non-missing Baseline and on-study measurement. Data after rescue excluded from analyses

Reporting Groups
  Description
Placebo Matching Dapagliflozin Placebo matching dapagliflozin: Tablets, Oral, 0 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
Dapagliflozin 10 mg Dapagliflozin: Tablets, Oral, 10 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.

Measured Values
    Placebo Matching Dapagliflozin     Dapagliflozin 10 mg  
Number of Participants Analyzed  
[units: participants]
  218     221  
Adjusted Mean Change From Baseline in Seated Systolic Blood Pressure for 12 Week Double-Blind Treatment Period - Randomized Participants  
[units: mmHg]
Mean ± Standard Error
   
Week 2 (N=218, 221)     -5.13  ± 0.9489     -7.93  ± 0.9357  
Week 4 (N=213, 220)     -6.05  ± 1.0232     -9.69  ± 1.0097  
Week 8 (N=205, 212)     -6.80  ± 1.0374     -11.38  ± 1.0251  
Week 12 (N=199, 205)     -7.62  ± 1.0701     -11.90  ± 1.0585  


Statistical Analysis 1 for Adjusted Mean Change From Baseline in Seated Systolic Blood Pressure for 12 Week Double-Blind Treatment Period - Randomized Participants
Groups [1] All groups
Method [2] Longitudinal repeated measures
P Value [3] 0.0002
Mean Difference (Final Values) [4] -4.28
Standard Error of the mean ± 1.1485
95% Confidence Interval ( -6.54 to -2.02 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Longitudinal repeated measures analysis using 'direct likelihood', with fixed categorical effects of treatment, week, treatment-by-week interaction, and randomization strata, as well as continuous fixed covariates of baseline SBP value and baseline SBP value-by-week interaction. Unstructured matrix for within-subject error variance-covariance used. 80% power to detect a difference of 4 mmHg in mean change from baseline, 75% power to meet both co-primary endpoints with overall Type I error.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Data from all weeks during the double-blind treatment period were included.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Endpoint was tested at alpha=0.05. Hierarchical closed testing procedure used.
[4] Other relevant estimation information:
  No text entered.



2.  Primary:   Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) for 12 Week Double-Blind Treatment Period - Randomized Participants   [ Time Frame: Baseline to Week 12 ]

Measure Type Primary
Measure Title Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) for 12 Week Double-Blind Treatment Period - Randomized Participants
Measure Description Adjusted mean change in glycosylated hemoglobin ( HbA1c) from baseline at Week 12 was calculated. HbA1c was measured as percent of hemoglobin by a central laboratory. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. HbA1c values were obtained at enrollment and lead-in (Day -28) periods, and at Day 1, Weeks 4, 8, and 12, in the double-blind period.
Time Frame Baseline to Week 12  
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.
All randomized participants who received double-blind medication and had non-missing Baseline and on-study measurement. Data after rescue included.

Reporting Groups
  Description
Placebo Matching Dapagliflozin Placebo matching dapagliflozin: Tablets, Oral, 0 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
Dapagliflozin 10 mg Dapagliflozin: Tablets, Oral, 10 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.

Measured Values
    Placebo Matching Dapagliflozin     Dapagliflozin 10 mg  
Number of Participants Analyzed  
[units: participants]
  214     219  
Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) for 12 Week Double-Blind Treatment Period - Randomized Participants  
[units: Percent of Hemoglobin]
Mean ± Standard Error
   
Week 4 (N=214, 219)     -0.06  ± 0.0498     -0.41  ± 0.0496  
Week 8 (N=207, 211)     -0.07  ± 0.0606     -0.58  ± 0.0602  
Week 12 (N=197, 204)     -0.02  ± 0.0673     -0.63  ± 0.0668  


Statistical Analysis 1 for Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) for 12 Week Double-Blind Treatment Period - Randomized Participants
Groups [1] All groups
Method [2] Longitudinal repeated measures
P Value [3] <0.0001
Mean Difference (Final Values) [4] -0.61
Standard Error of the mean ± 0.0773
95% Confidence Interval ( -0.76 to -0.46 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  A longitudinal repeated measures analysis used, with fixed categorical effects of treatment, week, treatment-by-week interaction, and randomization strata, continuous fixed covariates of baseline HbA1c value and baseline HbA1c value-by-week interaction. Only data up to Week 12 included. All data used in the model even if participants discontinued prior to Week 12. A heirarchical closed testing procedure (sequential) was used and testing performed since first primary endpoint was significant.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Endpoint was tested at alpha=0.05. Hierarchical closed testing procedure was used.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



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

Measure Type Secondary
Measure Title Adjusted Mean Change From Baseline in 24-hour Ambulatory Systolic Blood Pressure at Week 12 Last Observation Carried Forward (LOCF)
Measure Description Ambulatory 24 hour (hr) blood pressure monitoring (ABPM) was performed at baseline, which was during the lead-in period (between Day -7 and Day -1 prior to randomization) and 1 week prior to the Week 12 visit/end of treatment visit. If no Week 12 measurement was available, the last available earlier post-baseline measurement was used (LOCF) for analysis. Initiation of the 24-hr ABPM began between 6am and 11am to ensure trough BP measurements were obtained.The ABPM units were calibrated, and used per the manufacturer’s and central ABPM vendor instructions. BP was measured in mmHg. Participants had to have a mean 24-hour ABPM ≥ 130/80 mmHg prior to randomization. All medication was withheld on the morning of the study visit and brought to the visit site by the participant. Once the ABPM cuff was in place, all morning medication was taken while at the site.
Time Frame Baseline, Week 12  
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.
All randomized participants who received double-blind medication and had non-missing Baseline and Week 12 (LOCF) values. Data after rescue excluded from analyses.

Reporting Groups
  Description
Placebo Matching Dapagliflozin Placebo matching dapagliflozin: Tablets, Oral, 0 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
Dapagliflozin 10 mg Dapagliflozin: Tablets, Oral, 10 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.

Measured Values
    Placebo Matching Dapagliflozin     Dapagliflozin 10 mg  
Number of Participants Analyzed  
[units: participants]
  186     187  
Adjusted Mean Change From Baseline in 24-hour Ambulatory Systolic Blood Pressure at Week 12 Last Observation Carried Forward (LOCF)  
[units: mmHg]
Mean ± Standard Error
  -6.88  ± 1.5793     -11.33  ± 1.6031  


Statistical Analysis 1 for Adjusted Mean Change From Baseline in 24-hour Ambulatory Systolic Blood Pressure at Week 12 Last Observation Carried Forward (LOCF)
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.0012
Mean Difference (Final Values) [4] -4.45
Standard Error of the mean ± 1.3680
95% Confidence Interval ( -7.14 to -1.76 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  ANCOVA model with treatment group as an effect and baseline value and randomization strata as a covariate was used. By applying sequential testing procedure, the testing was performed since the prior endpoint was significant.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] 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 alpha=0.05.
[4] Other relevant estimation information:
  No text entered.



4.  Secondary:   Adjusted Mean Change From Baseline in Seated Diastolic Blood Pressure (DBP) for 12 Week Double-Blind Treatment Period - Randomized Participants   [ Time Frame: Baseline to Week 12 ]

Measure Type Secondary
Measure Title Adjusted Mean Change From Baseline in Seated Diastolic Blood Pressure (DBP) for 12 Week Double-Blind Treatment Period - Randomized Participants
Measure Description Diastolic BP was measured in millimeters of mercury (mmHg) on Day -1, Day 1, Weeks 2, 4, 8, and 12 of the Double Blind Period. Diastolic BP values were obtained after the participant was seated for quietly for 10 minutes; a mean of 3 replicate measurements was taken 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 obtained (total = 5) and incorporated into the calculated mean. BP was measured in both arms. If the pressure was higher in one arm than the other, then this arm was used; if no difference, the participant’s dominant arm was used for all future BP measurements. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. Participants refrained from ingestion of caffeine, alcohol, or nicotine at least 10 hours prior to their visit and having their BP measured.
Time Frame Baseline to Week 12  
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.
All randomized participants who received double-blind medication and had non-missing Baseline and on-study measurement. Data after rescue excluded from analyses

Reporting Groups
  Description
Placebo Matching Dapagliflozin Placebo matching dapagliflozin: Tablets, Oral, 0 mg, once daily, Up to 12 weeks.Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
Dapagliflozin 10 mg Dapagliflozin: Tablets, Oral, 10 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.

Measured Values
    Placebo Matching Dapagliflozin     Dapagliflozin 10 mg  
Number of Participants Analyzed  
[units: participants]
  218     221  
Adjusted Mean Change From Baseline in Seated Diastolic Blood Pressure (DBP) for 12 Week Double-Blind Treatment Period - Randomized Participants  
[units: mmHg]
Mean ± Standard Error
   
Week 2 (N=218, 221)     -3.84  ± 0.5691     -5.22  ± 0.5613  
Week 4 (N=213, 220)     -4.28  ± 0.5894     -5.57  ± 0.5818  
Week 8 (N=205, 212)     -4.76  ± 0.6247     -6.53  ± 0.6170  
Week 12 (N=199, 205)     -5.33  ± 0.6377     -6.30  ± 0.6308  


Statistical Analysis 1 for Adjusted Mean Change From Baseline in Seated Diastolic Blood Pressure (DBP) for 12 Week Double-Blind Treatment Period - Randomized Participants
Groups [1] All groups
Method [2] Longitudinal repeated measures
P Value [3] 0.1619
Mean Difference (Final Values) [4] -0.97
Standard Error of the mean ± 0.6900
95% Confidence Interval ( -2.32 to 0.39 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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 seated diastolic BP value and baseline seated diastolic BP value by week interaction.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] 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 alpha=0.05.
[4] Other relevant estimation information:
  No text entered.



5.  Secondary:   Adjusted Mean Change From Baseline in 24-hr Ambulatory Diastolic Blood Pressure at Week 12 (LOCF)   [ Time Frame: Baseline, Week 12 ]

Measure Type Secondary
Measure Title Adjusted Mean Change From Baseline in 24-hr Ambulatory Diastolic Blood Pressure at Week 12 (LOCF)
Measure Description Ambulatory 24 hour (hr) BP monitoring (ABPM) was performed at baseline, which was during the lead-in period (between Day -7 and Day -1 prior to randomization) and 1 week prior to the Week 12 visit/end of treatment visit. If no Week 12 measurement was available, the last available earlier post-baseline measurement was used (LOCF). Initiation of the 24-hr ABPM began between 6am and 11am to ensure trough BP measurements were obtained. The ABPM units were calibrated, and used per the manufacturer’s and central ABPM vendor instructions. BP was measured in mmHg. Participants had to have a mean 24-hour ABPM ≥ 130/80 mmHg prior to randomization. All medication was withheld on the morning of the study visit and brought to the visit site by the participant. Once the ABPM cuff was in place, all morning medication was taken while at the site.
Time Frame Baseline, Week 12  
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.
All randomized participants who received double-blind medication and had non-missing Baseline and on-study measurement (Week 12 LOCF). Data after rescue excluded from analyses.

Reporting Groups
  Description
Placebo Matching Dapagliflozin Placebo matching dapagliflozin: Tablets, Oral, 0 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
Dapagliflozin 10 mg Dapagliflozin: Tablets, Oral, 10 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.

Measured Values
    Placebo Matching Dapagliflozin     Dapagliflozin 10 mg  
Number of Participants Analyzed  
[units: participants]
  186     187  
Adjusted Mean Change From Baseline in 24-hr Ambulatory Diastolic Blood Pressure at Week 12 (LOCF)  
[units: mmHg]
Mean ± Standard Error
  -5.57  ± 1.0042     -7.56  ± 1.0183  


Statistical Analysis 1 for Adjusted Mean Change From Baseline in 24-hr Ambulatory Diastolic Blood Pressure at Week 12 (LOCF)
Groups [1] All groups
Method [2] ANCOVA
Mean Difference (Final Values) [3] -1.99
Standard Error of the mean ± 0.8635
95% Confidence Interval ( -3.68 to -0.29 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  ANCOVA model with treatment group as an effect and baseline value and randomization strata as a covariate. A hierarchical closed testing procedure was implemented to control the family-wise type I error rate related to the co-primary and secondary endpoints at the 2-sided 0.05 level. Statistical testing of this endpoint was not performed since the prior secondary endpoint was not statistically significant.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Other relevant estimation information:
  No text entered.



6.  Secondary:   Adjusted Mean Change From Baseline in Serum Uric Acid at Week 12 in Double-Blind Treatment Period - Randomized Participants   [ Time Frame: Baseline, Week 12 ]

Measure Type Secondary
Measure Title Adjusted Mean Change From Baseline in Serum Uric Acid at Week 12 in Double-Blind Treatment Period - Randomized Participants
Measure Description Adjusted mean change in serum uric acid from baseline at Week 12 was calculated. Serum uric acid was measured in milligrams per deciliter (mg/dL) by a central laboratory. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. Serum uric acid measurements were obtained at qualification and lead-in (Day -28) periods, and at Day 1, Weeks 4, 8, and 12, in the double-blind period but only the change from baseline at Week 12 was considered a secondary endpoint and is presented.
Time Frame Baseline, Week 12  
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.
All randomized participants who received double-blind medication and had non-missing Baseline and on-study measurement. Data after rescue was included.

Reporting Groups
  Description
Placebo Matching Dapagliflozin Placebo matching dapagliflozin: Tablets, Oral, 0 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
Dapagliflozin 10 mg Dapagliflozin: Tablets, Oral, 10 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.

Measured Values
    Placebo Matching Dapagliflozin     Dapagliflozin 10 mg  
Number of Participants Analyzed  
[units: participants]
  210     219  
Adjusted Mean Change From Baseline in Serum Uric Acid at Week 12 in Double-Blind Treatment Period - Randomized Participants  
[units: mg/dL]
Mean ± Standard Error
  -0.03  ± 0.0890     -0.43  ± 0.0883  


Statistical Analysis 1 for Adjusted Mean Change From Baseline in Serum Uric Acid at Week 12 in Double-Blind Treatment Period - Randomized Participants
Groups [1] All groups
Method [2] lLongitudinal repeated measures
Mean Difference (Final Values) [3] -0.40
Standard Error of the mean ± 0.0858
95% Confidence Interval ( -0.57 to -0.23 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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 serum uric acid value and baseline seated serum uric acid value by week interaction. By applying sequential testing procedure at alpha=0.05, no testing was performed since the prior secondary endpoint was not significant.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Other relevant estimation information:
  No text entered.



7.  Secondary:   Number of Participants With Deaths,Serious Adverse Events (SAEs), Adverse Events (AEs), Hypoglycemia Events, Discontinuation Due to AEs, SAEs and Hypoglycemia, During the 12 Week Double Blind Period, Including Data After Rescue   [ Time Frame: Baseline to last dose of 12 weeks of double blind medication plus 30 days if SAE or plus 4 days if AE/hypoglycemic event ]

Measure Type Secondary
Measure Title Number of Participants With Deaths,Serious Adverse Events (SAEs), Adverse Events (AEs), Hypoglycemia Events, Discontinuation Due to AEs, SAEs and Hypoglycemia, During the 12 Week Double Blind Period, Including Data After Rescue
Measure Description Medical Dictionary for Regulatory Activities (MedDRA), version 15.1 AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related=having certain, probable, possible, or missing relationship to study drug as per the investigator. Events captured from baseline to last double blind dose plus 4 days for AEs, plus 30 days for SAEs during the Double Blind 12 Week Period. Only hypoglycemia reported as an SAE is included in AE/SAE categories . All reported hypoglycemia events within 4 days of last day of treatment are included as hypoglycemic events.
Time Frame Baseline to last dose of 12 weeks of double blind medication plus 30 days if SAE or plus 4 days if AE/hypoglycemic event  
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.
Randomized participants who received double-blind study medication in the double-blind period.

Reporting Groups
  Description
Placebo Matching Dapagliflozin Placebo matching dapagliflozin: Tablets, Oral, 0 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
Dapagliflozin 10 mg Dapagliflozin: Tablets, Oral, 10 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
Dagagliflozin 5 mg (Arm Discontinued With Amendment 8)

Dapagliflozin: Tablets, Oral, 5 mg, once a day for up to12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.

This arm was discontinued with Amendment 8 to the protocol (implemented 1 November 2011) and the other 2 arms continued to enroll. This arm is not included in primary and secondary efficacy analysis.


Measured Values
    Placebo Matching Dapagliflozin     Dapagliflozin 10 mg     Dagagliflozin 5 mg (Arm Discontinued With Amendment 8)  
Number of Participants Analyzed  
[units: participants]
  224     225     133  
Number of Participants With Deaths,Serious Adverse Events (SAEs), Adverse Events (AEs), Hypoglycemia Events, Discontinuation Due to AEs, SAEs and Hypoglycemia, During the 12 Week Double Blind Period, Including Data After Rescue  
[units: participants]
     
Deaths     0     0     0  
SAEs     2     6     1  
Related SAEs     1     0     0  
AEs     93     98     60  
Hypoglycemia AEs     6     13     2  
Related AEs     12     15     8  
Discontinued due to AE     4     1     2  
Discontinued due to SAE     1     0     1  
Discontinued due to Hypoglycemia     0     0     0  

No statistical analysis provided for Number of Participants With Deaths,Serious Adverse Events (SAEs), Adverse Events (AEs), Hypoglycemia Events, Discontinuation Due to AEs, SAEs and Hypoglycemia, During the 12 Week Double Blind Period, Including Data After Rescue



8.  Secondary:   Number of Participants With Marked Chemistry Laboratory Abnormalities in 12 Week Double Blind Treatment Period, Including Data After Rescue   [ Time Frame: Baseline (Day 1) to last dose double blind medication (Week 12) plus 4 days ]

Measure Type Secondary
Measure Title Number of Participants With Marked Chemistry Laboratory Abnormalities in 12 Week Double Blind Treatment Period, Including Data After Rescue
Measure Description Samples obtained: Day 1, Weeks 4, 8,12 in Double Blind Period. Baseline: last assessment prior to start of first dose of double-blind treatment. Pretreatment (PreRX); grams per deciliter (g/dL); upper limit of normal (ULN); milliequivalent per liter (mEq/L); greater than (>) less than (<); Units per liter (U/L), Marked abnormality Low (High): hemoglobin <6 (>18 females or >20 males) g/dL; creatinine (>=1.5*preRX, >=2.5 mg/dL); glucose < 54 or (> 350) mg/dL; albumin <= 2 or (> 6) g/dL; creatine kinase >5*ULN; albumin/creatinine ratio (>1800 mg/G); calcium <7.5 (>1 and >0.5 from PreRX) mg/dL; bicarbonate <=13 meq/dL; potassium <=2.5 (>6) meq/L; magnesium <1 (>4) mEq/L; sodium < 130 mEq/L (>150 mEq/L; phosphorus (>=5.6 mg/dL age 17-65, >=5.1 is >=66 years); Albumin/creatinine ratio (>1800 mg/g). Note: Hepatic tests are presented separately in next outcome measure.
Time Frame Baseline (Day 1) to last dose double blind medication (Week 12) plus 4 days  
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.
N=All randomized participants who received at least one dose of double-blind medication. n=all treated participants who had non-missing Baseline and on-study measurement. Data after rescue included.

Reporting Groups
  Description
Placebo Matching Dapagliflozin Placebo matching dapagliflozin: Tablets, Oral, 0 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
Dapagliflozin 10 mg Dapagliflozin: Tablets, Oral, 10 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.

Measured Values
    Placebo Matching Dapagliflozin     Dapagliflozin 10 mg  
Number of Participants Analyzed  
[units: participants]
  218     223  
Number of Participants With Marked Chemistry Laboratory Abnormalities in 12 Week Double Blind Treatment Period, Including Data After Rescue  
[units: participants]
   
Hemoglobin High >18 g/dL (n=218, 223)     1     0  
Creatinine >=1.5PreRx (n=218,223)     1     3  
Glucose, plasma unspecif <54 mg/dL (n=218,222)     0     1  
Glucose, plasma unspecif >350 mg/dL (n=218,222)     2     1  
Creatine Kinase >5*ULN (n=218,223)     2     0  
Creatine Kinase >10*ULN (n=218,223)     1     0  
Calcium, total <7.5 mg (n=218,223)     0     1  
Potassium, serum≥6 mEq/L (n=218,222)     0     4  
Magnesium <1 mEq/L (n=218,223)     0     2  
Sodium, serum <130 mEq/L (n=218,222)     1     0  
Sodium, serum >150 mEq/L (n=218,222)     1     1  
Phosphorus inorganic High (n=218,223)     0     2  
Albumin/Creatinine Ratio High (n=218, 223)     5     3  

No statistical analysis provided for Number of Participants With Marked Chemistry Laboratory Abnormalities in 12 Week Double Blind Treatment Period, Including Data After Rescue



9.  Secondary:   Number of Participants With Elevated Liver Laboratory Tests in Participants Treated With Double Blind 10 mg Dapagliflozin or Placebo , Including Data After Rescue   [ Time Frame: Baseline (Day 1) to last dose double blind medication (Week 12) Plus 30 days ]

Measure Type Secondary
Measure Title Number of Participants With Elevated Liver Laboratory Tests in Participants Treated With Double Blind 10 mg Dapagliflozin or Placebo , Including Data After Rescue
Measure Description Laboratories were obtained at Day 1, Weeks 4, 8 and 12 in the Double Blind Period. Baseline: last assessment prior to start of first dose of double-blind treatment. Includes laboratory values measured after the first date of double-blind treatment and up to and including the last day of double blind treatment plus 30 days. Upper limit of normal (ULN);, alanine aminotransferase (ALT); aspartate aminotransferase (AST); alkaline phosphatase (ALP). Marked abnormality (High): AST and ALT (>3*ULN); ALP (>1.5*ULN); bilirubin (>1.5*ULN). Participants with abnormally elevated liver laboratory tests were followed 30 days after the last dose of study drug.
Time Frame Baseline (Day 1) to last dose double blind medication (Week 12) Plus 30 days  
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.
N=All randomized participants who received at least 1 dose of study medication. n=number of participants treated with double blind study medication with at least one non-missing post-baseline value. Data after rescue included.

Reporting Groups
  Description
Placebo Matching Dapagliflozin Placebo matching dapagliflozin: Tablets, Oral, 0 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
Dapagliflozin 10 mg Dapagliflozin: Tablets, Oral, 10 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.

Measured Values
    Placebo Matching Dapagliflozin     Dapagliflozin 10 mg  
Number of Participants Analyzed  
[units: participants]
  221     224  
Number of Participants With Elevated Liver Laboratory Tests in Participants Treated With Double Blind 10 mg Dapagliflozin or Placebo , Including Data After Rescue  
[units: participants]
   
AST >3*ULN (n=221, 224)     0     3  
AST >5*ULN (n=221, 224)     0     1  
AST >10*ULN (n=221, 224)     0     1  
AST >20*ULN (n=221, 224)     0     1  
ALT >3*ULN (n=221, 224)     0     3  
ALT >5*ULN (n=221, 224)     0     2  
ALT >10*ULN (n=221, 224)     0     1  
ALT >20*ULN (n=221, 224)     0     1  
Total Bilirubin >1.5*ULN (n=221, 224)     0     2  
Total Bilirubin >2*ULN (n=221, 224)     0     1  
ALP >1.5*ULN (n=221, 224)     5     4  

No statistical analysis provided for Number of Participants With Elevated Liver Laboratory Tests in Participants Treated With Double Blind 10 mg Dapagliflozin or Placebo , Including Data After Rescue



10.  Secondary:   Number of Participants With Normal or Abnormal Electrocardiogram Summary Tracing at Week 12 (LOCF), Including Data After Rescue   [ Time Frame: Baseline, Week 12 ]

Measure Type Secondary
Measure Title Number of Participants With Normal or Abnormal Electrocardiogram Summary Tracing at Week 12 (LOCF), Including Data After Rescue
Measure Description 12-Lead electrocardiograms (ECGs) were performed at Enrollment, Day 1 of Double Blind Period and Week 12/End of treatment visit (last observation carried forward) on participants who were supine. ECGs were assessed by the investigator as normal or abnormal. Baseline (BL) was Day 1 prior to dosing or last observation prior to dosing.
Time Frame Baseline, 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.
N= All randomized participants who received double-blind medication. Data after rescue included.

Reporting Groups
  Description
Placebo Matching Dapagliflozin Placebo matching dapagliflozin: Tablets, Oral, 0 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
Dapagliflozin 10 mg Dapagliflozin: Tablets, Oral, 10 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.

Measured Values
    Placebo Matching Dapagliflozin     Dapagliflozin 10 mg  
Number of Participants Analyzed  
[units: participants]
  224     225  
Number of Participants With Normal or Abnormal Electrocardiogram Summary Tracing at Week 12 (LOCF), Including Data After Rescue  
[units: participants]
   
Baseline normal/Week 12 normal     137     130  
Baseline normal/Week 12 abnormal     9     10  
Baseline normal/ Week 12 not reported     0     0  
Baseline abnormal/Week 12 normal     10     22  
Baselline abnormal/Week 12 abnormal     48     50  
Baseline abnormal/Week 12 not reported     0     0  
Baseline not reported/Week 12 normal     0     0  
Baseline not reported/Week 12 abnormal     0     0  
Baseline not reported/Week 12 not reported     20     13  

No statistical analysis provided for Number of Participants With Normal or Abnormal Electrocardiogram Summary Tracing at Week 12 (LOCF), Including Data After Rescue



11.  Secondary:   Proportion of Participants With Orthostatic Hypotension at Baseline and Week 12, Including Data After Rescue   [ Time Frame: Baseline (Day 1), Week 12 ]

Measure Type Secondary
Measure Title Proportion of Participants With Orthostatic Hypotension at Baseline and Week 12, Including Data After Rescue
Measure Description Orthostatic hypotension was defined as a decrease from supine to standing of > 20 mmHg in systolic BP or >10 mmHg in diastolic BP. Proportion was calculated from number of participants with orthostatic hypotension (n) divided by the number of treated participants (N). n/N presented as a percent (%). Baseline was Day 1 of the double blind Period. Measurements for orthostatic hypotension were taken on Day 1 and at Week 12 visit and does not reflect AEs reported by the investigator.
Time Frame Baseline (Day 1), 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.
N= All randomized participants who received double-blind medication and had non-missing Week (t) values. Week 12 includes participants with orthostatic hypotension during Week 12 visit window. Data after rescue included.

Reporting Groups
  Description
Placebo Matching Dapagliflozin Placebo matching dapagliflozin: Tablets, Oral, 0 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
Dapagliflozin 10 mg Dapagliflozin: Tablets, Oral, 10 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.

Measured Values
    Placebo Matching Dapagliflozin     Dapagliflozin 10 mg  
Number of Participants Analyzed  
[units: participants]
  220     222  
Proportion of Participants With Orthostatic Hypotension at Baseline and Week 12, Including Data After Rescue  
[units: Percent of Participants]
   
Baseline n/N (2/220, 2/222)     0.9     0.9  
Week 12 n/N (4/199, 7/203)     2.0     3.4  

No statistical analysis provided for Proportion of Participants With Orthostatic Hypotension at Baseline and Week 12, Including Data After Rescue




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide 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
Totality of data from dapagliflozin development program as of 1 NOV 2011 showed 10 mg dapagliflozin dose provided optimal efficacy, was safe and well tolerated for the general Type 2 diabetes population, allowing the 5 mg arm to be discontinued.


  More Information
  Hide More Information

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: NCT01195662     History of Changes
Other Study ID Numbers: MB102-077 ST, 2010-019798-13
Study First Received: September 3, 2010
Results First Received: February 7, 2014
Last Updated: April 28, 2014
Health Authority: United States: Food and Drug Administration
Mexico: Secretaria de Salud
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
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Denmark: Ministry of Health