Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01392677
Recruitment Status : Completed
First Posted : July 12, 2011
Results First Posted : December 27, 2013
Last Update Posted : March 12, 2014
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Type 2 Diabetes Mellitus
High HbA1c Level
Inadequate Glycaemic Control
Interventions Drug: dapagliflozin
Drug: placebo
Enrollment 311
Recruitment Details 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 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.
Arm/Group Title Placebo Plus Metformin Plus Sulfonylurea Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea
Hide Arm/Group Description Placebo once daily plus background combination of metformin and sulfonylurea Dapagliflozin 10mg once daily plus background combination of metformin and sulfonylurea
Period Title: Overall Study
Started 109 109
Completed 101 101
Not Completed 8 8
Reason Not Completed
Adverse Event             3             1
Withdrawal by Subject             0             2
Incorrect enrollment             2             3
Other reason             3             2
Arm/Group Title Placebo Plus Metformin Plus Sulfonylurea Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea Total
Hide Arm/Group Description Placebo once daily plus background combination of metformin and sulfonylurea Dapagliflozin 10mg once daily plus background combination of metformin and sulfonylurea Total of all reporting groups
Overall Number of Baseline Participants 108 108 216
Hide Baseline Analysis Population Description
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.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 108 participants 108 participants 216 participants
60.9  (9.24) 61.1  (9.65) 61.0  (9.42)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 108 participants 108 participants 216 participants
Female
48
  44.4%
62
  57.4%
110
  50.9%
Male
60
  55.6%
46
  42.6%
106
  49.1%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 108 participants 108 participants 216 participants
White 102 104 206
Black/African American 1 0 1
Asian 4 3 7
Other 1 1 2
Body Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 108 participants 108 participants 216 participants
90.07  (16.175) 88.57  (17.584) 89.32  (16.872)
Body Mass Index  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 108 participants 108 participants 216 participants
32.02  (4.581) 31.93  (4.840) 31.97  (4.702)
Glycosylated hemoglobin A1c (HbA1c)  
Mean (Standard Deviation)
Unit of measure:  Percent
Number Analyzed 108 participants 108 participants 216 participants
8.24  (0.865) 8.08  (0.912) 8.16  (0.890)
Fasting Plasma Glucose  
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 108 participants 108 participants 216 participants
180.2  (43.13) 167.4  (43.32) 173.8  (43.61)
Fasting C-Peptide  
Mean (Standard Deviation)
Unit of measure:  ng/mL
Number Analyzed 108 participants 108 participants 216 participants
2.5  (0.98) 2.5  (1.06) 2.5  (1.02)
1.Primary Outcome
Title Adjusted Mean Change From Baseline in HbA1c Levels
Hide Description To compare the change from baseline in HbA1c to week 24 between dapagliflozin 10 mg in combination with metformin and sulfonylurea and placebo in combination with metformin and sulfonylurea.
Time Frame Baseline to week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set, participants with non-missing baseline and week 24 values
Arm/Group Title Placebo Plus Metformin Plus Sulfonylurea Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea
Hide Arm/Group Description:
Placebo once daily plus background combination of metformin and sulfonylurea
Dapagliflozin 10mg once daily plus background combination of metformin and sulfonylurea
Overall Number of Participants Analyzed 108 108
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Percent
-0.17
(-0.31 to -0.02)
-0.86
(-1.00 to -0.72)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Plus Metformin Plus Sulfonylurea, Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea
Comments H0: mean(treat) minus mean(placebo) = 0 versus the alternative HA: mean(treat) minus mean(placebo) =/= 0
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Significant at alpha=0.05 (2-sided). A hierarchical closed testing procedure was used to control Type I error across the primary & key secondary objectives
Method Mixed Models Analysis
Comments Longitudinal repeated measures model using mixed model with treatment group, baseline value, week and week*treatment and week*baseline
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.69
Confidence Interval (2-Sided) 95%
-0.89 to -0.49
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.1022
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Adjusted Mean Change From Baseline in FPG
Hide Description To compare the change from baseline in fasting plasma glucose (FPG) to week 24 (LOCF) between dapagliflozin and placebo
Time Frame Baseline to week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set, participants with non-missing baseline and week 24 (LOCF) values
Arm/Group Title Placebo Plus Metformin Plus Sulfonylurea Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea
Hide Arm/Group Description:
Placebo once daily plus background combination of metformin and sulfonylurea
Dapagliflozin 10mg once daily plus background combination of metformin and sulfonylurea
Overall Number of Participants Analyzed 107 108
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mg/dL
-0.78
(-7.56 to 6.01)
-34.23
(-40.98 to -27.48)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Plus Metformin Plus Sulfonylurea, Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea
Comments H0: mean(treat) minus mean(placebo) = 0 versus the alternative HA: mean(treat) minus mean(placebo) =/= 0
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Significant at alpha=0.05 (2-sided). A hierarchical closed testing procedure was used to control Type I error across the primary & key secondary objectives
Method ANCOVA
Comments with treatment group as effect and baseline value as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -33.45
Confidence Interval (2-Sided) 95%
-43.08 to -23.82
Parameter Dispersion
Type: Standard Error of the mean
Value: 4.8846
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Adjusted Mean Change From Baseline in Total Body Weight
Hide Description To compare the change from baseline in total body weight to week 24 (LOCF) between dapagliflozin and placebo
Time Frame Baseline to week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set, participants with non-missing baseline and week 24 (LOCF) values
Arm/Group Title Placebo Plus Metformin Plus Sulfonylurea Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea
Hide Arm/Group Description:
Placebo once daily plus background combination of metformin and sulfonylurea
Dapagliflozin 10mg once daily plus background combination of metformin and sulfonylurea
Overall Number of Participants Analyzed 108 108
Least Squares Mean (95% Confidence Interval)
Unit of Measure: kg
-0.58
(-1.09 to -0.07)
-2.65
(-3.16 to -2.14)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Plus Metformin Plus Sulfonylurea, Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea
Comments H0: mean(treat) minus mean(placebo) = 0 versus the alternative HA: mean(treat) minus mean(placebo) =/= 0
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Significant at alpha=0.05 (2-sided). A hierarchical closed testing procedure was used to control Type I error across the primary & key secondary objectives
Method ANCOVA
Comments with treatment group as effect and baseline value as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.07
Confidence Interval (2-Sided) 95%
-2.79 to -1.35
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.3651
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Proportion of Participants With HbA1c Value < 7.0% at Week 24 (LOCF)
Hide Description To compare the proportion of subjects achieving a therapeutic glycemic response, defined as HbA1c <7.0%, at week 24 (LOCF) between dapagliflozin and placebo
Time Frame Baseline to week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set, participants with non-missing baseline and week 24 (LOCF) values
Arm/Group Title Placebo Plus Metformin Plus Sulfonylurea Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea
Hide Arm/Group Description:
Placebo once daily plus background combination of metformin and sulfonylurea
Dapagliflozin 10mg once daily plus background combination of metformin and sulfonylurea
Overall Number of Participants Analyzed 108 108
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Percentage of participants
11.1
(5.4 to 16.8)
31.8
(23.3 to 40.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Plus Metformin Plus Sulfonylurea, Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea
Comments H0: proportion(treat) minus proportion (placebo) = 0 versus the alternative HA: proportion (treat) minus proportion (placebo) =/= 0
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Significant at alpha=0.05 (2-sided). A hierarchical closed testing procedure was used to control Type I error across the primary & key secondary objectives
Method Regression, Logistic
Comments Based on methodology of Zhang, Tsiatis & Davidian and Tsiatis, Davidian, Zhang & Lu, with adjustment for baseline value
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 20.7
Confidence Interval (2-Sided) 95%
10.7 to 30.6
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.056
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Adjusted Mean Change From Baseline in Seated Systolic Blood Pressure
Hide Description To compare the change from baseline in seated systolic blood pressure (SBP) to week 8 (LOCF) between dapagliflozin and placebo
Time Frame Baseline to week 8
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set, participants with non-missing baseline and week 8 (LOCF) values
Arm/Group Title Placebo Plus Metformin Plus Sulfonylurea Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea
Hide Arm/Group Description:
Placebo once daily plus background combination of metformin and sulfonylurea
Dapagliflozin 10mg once daily plus background combination of metformin and sulfonylurea
Overall Number of Participants Analyzed 105 105
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mmHg
-0.27
(-2.60 to 2.05)
-4.04
(-6.36 to -1.72)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Plus Metformin Plus Sulfonylurea, Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea
Comments H0: mean(treat) minus mean(placebo) = 0 versus the alternative HA: mean(treat) minus mean(placebo) =/= 0
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.025
Comments Significant at alpha=0.05 (2-sided). A hierarchical closed testing procedure was used to control Type I error across the primary & key secondary objectives
Method ANCOVA
Comments with treatment group as effect and baseline value as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.76
Confidence Interval (2-Sided) 95%
-7.05 to -0.48
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.6677
Estimation Comments [Not Specified]
Time Frame Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 24-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including the start date of extension period if earlier.
Adverse Event Reporting Description Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at a study visit was assessed in comparison to the status at study entry.
 
Arm/Group Title Placebo Plus Metformin Plus Sulfonylurea Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea
Hide Arm/Group Description Placebo once daily plus background combination of metformin and sulfonylurea Dapagliflozin 10mg once daily plus background combination of metformin and sulfonylurea
All-Cause Mortality
Placebo Plus Metformin Plus Sulfonylurea Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Placebo Plus Metformin Plus Sulfonylurea Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea
Affected / at Risk (%) Affected / at Risk (%)
Total   6/109 (5.50%)   1/109 (0.92%) 
Cardiac disorders     
aortic valve stenosis  1  1/109 (0.92%)  0/109 (0.00%) 
arrhythmia  1  1/109 (0.92%)  0/109 (0.00%) 
Infections and infestations     
diabetic gangrene  1  1/109 (0.92%)  0/109 (0.00%) 
Musculoskeletal and connective tissue disorders     
sympathetic posterior cervical syndrome  1  1/109 (0.92%)  0/109 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
renal cell carcinoma  1  1/109 (0.92%)  0/109 (0.00%) 
Renal and urinary disorders     
calculus ureteric  1  1/109 (0.92%)  0/109 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
chronic obstructive pulmonary disease  1  0/109 (0.00%)  1/109 (0.92%) 
Vascular disorders     
peripheral arterial occlusive disease  1  1/109 (0.92%)  0/109 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Plus Metformin Plus Sulfonylurea Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea
Affected / at Risk (%) Affected / at Risk (%)
Total   7/109 (6.42%)   5/109 (4.59%) 
Infections and infestations     
urinary tract infection  1  7/109 (6.42%)  5/109 (4.59%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.1
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.
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.
If an Investigator requests permission to publish data from this study any such publication is to be agreed with AstraZeneca (AZ) in advance. The investigator agrees to provide AZ as soon as possible with drafts of proposed publications. Unless otherwise agreed, AZ shall have a period of 60 days from receipt of the proposed final manuscript to review it and may within such time require that submission for publication of the manuscript be delayed in order for AZ to file patent applications.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Eva Johnsson
Organization: AstraZeneca
EMail: ClinicalTrialTransparency@astrazeneca.com
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01392677    
Other Study ID Numbers: D1693C00005
First Submitted: July 11, 2011
First Posted: July 12, 2011
Results First Submitted: November 5, 2013
Results First Posted: December 27, 2013
Last Update Posted: March 12, 2014