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Trial to Evaluate the Efficacy and Safety of Dapagliflozin in Japanese Type 2 Diabetes Mellitus Patients

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: NCT00972244
Recruitment Status : Completed
First Posted : September 4, 2009
Results First Posted : October 14, 2013
Last Update Posted : October 14, 2013
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Type 2 Diabetes Mellitus
Interventions Drug: Dapagliflozin
Drug: Placebo
Enrollment 417
Recruitment Details Enrollment: 417; randomized: 279 Study Start Date: August 2009 Study Completion Date: May 2010 Primary Completion Date: May 2010
Pre-assignment Details  
Arm/Group Title 1mg Dapagliflozin 2.5mg Dapagliflozin 5mg Dapagliflozin 10mg Dapagliflozin Placebo
Hide Arm/Group Description Dapagliflozin tablet 1 mg once daily Dapagliflozin tablet 2.5 mg once daily Dapagliflozin tablet 5 mg once daily Dapagliflozin tablet 10 mg once daily Placebo Comparator
Period Title: Overall Study
Started 59 56 58 52 54
Completed 54 51 56 52 45
Not Completed 5 5 2 0 9
Reason Not Completed
Incorrect Enrolment             1             0             0             0             0
Adverse Event             0             1             1             0             0
Subject No Longer Meets Study Criteria             2             2             0             0             5
Withdrawal by Subject             1             2             1             0             1
Safety             0             0             0             0             1
Death             1             0             0             0             0
Various             0             0             0             0             2
Arm/Group Title 1mg Dapagliflozin 2.5mg Dapagliflozin 5mg Dapagliflozin 10mg Dapagliflozin Placebo Total
Hide Arm/Group Description Dapagliflozin tablet 1 mg once daily Dapagliflozin tablet 2.5 mg once daily Dapagliflozin tablet 5 mg once daily Dapagliflozin tablet 10 mg once daily Placebo Comparator Total of all reporting groups
Overall Number of Baseline Participants 59 56 58 52 54 279
Hide Baseline Analysis Population Description
Full Analysis Set defined as all randomised participants (as randomized) who received at least one dose of double-blind study medication, who have a non-missing baseline value and at least one post-baseline efficacy value for at least one efficacy variable during double-blind period.
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 59 participants 56 participants 58 participants 52 participants 54 participants 279 participants
55.9  (9.73) 57.7  (9.33) 58.0  (9.50) 56.5  (11.47) 58.4  (9.97) 57.3  (9.98)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 59 participants 56 participants 58 participants 52 participants 54 participants 279 participants
Female
12
  20.3%
17
  30.4%
11
  19.0%
13
  25.0%
11
  20.4%
64
  22.9%
Male
47
  79.7%
39
  69.6%
47
  81.0%
39
  75.0%
43
  79.6%
215
  77.1%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Japanese Number Analyzed 59 participants 56 participants 58 participants 52 participants 54 participants 279 participants
59 56 58 52 54 279
HBA1C  
Mean (Standard Deviation)
Unit of measure:  Percent
Number Analyzed 59 participants 56 participants 58 participants 52 participants 54 participants 279 participants
8.10  (0.785) 7.92  (0.740) 8.05  (0.660) 8.18  (0.690) 8.12  (0.714) 8.07  (0.720)
1.Primary Outcome
Title Adjusted Mean Change in HbA1c Levels
Hide Description The primary efficacy endpoint is the absolute change in HbA1c from baseline to Week 12 or the last post-baseline measurement prior to Week 12, if no Week 12 assessment is available.
Time Frame Baseline to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set, participants with non-missing baseline and Week 12 (LOCF) values
Arm/Group Title 1mg Dapagliflozin 2.5mg Dapagliflozin 5mg Dapagliflozin 10mg Dapagliflozin Placebo
Hide Arm/Group Description:
Dapagliflozin tablet 1 mg once daily
Dapagliflozin tablet 2.5 mg once daily
Dapagliflozin tablet 5 mg once daily
Dapagliflozin tablet 10 mg once daily
Placebo Comparator
Overall Number of Participants Analyzed 59 54 58 52 52
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percent
-0.12
(-0.25 to 0.01)
-0.10
(-0.24 to 0.04)
-0.37
(-0.50 to -0.23)
-0.44
(-0.58 to -0.29)
0.35
(0.21 to 0.49)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1mg Dapagliflozin, Placebo
Comments The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0 (with alpha = 0.015 applying Dunnett's adjustment, two-sided)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments significant at alpha=0.015 (2-sided) applying Dunnett's adjustment. A sequential closed testing procedure was used to control Type I error rate across the primary and key secondary endpoints.
Method ANCOVA
Comments with treatment group (all treatment groups included) as fixed effect and baseline value as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.47
Confidence Interval (2-Sided) 95%
-0.67 to -0.28
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0987
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 2.5mg Dapagliflozin, Placebo
Comments The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0 (with alpha = 0.015 applying Dunnett's adjustment, two-sided)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments significant at alpha=0.015 (2-sided) applying Dunnett's adjustment. A sequential closed testing procedure was used to control Type I error rate across the primary and key secondary endpoints.
Method ANCOVA
Comments with treatment group (all treatment groups included) as fixed effect and baseline value as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.45
Confidence Interval (2-Sided) 95%
-0.65 to -0.26
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.1009
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 5mg Dapagliflozin, Placebo
Comments The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0 (with alpha = 0.015 applying Dunnett's adjustment, two-sided)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments significant at alpha=0.015 (2-sided) applying Dunnett's adjustment. A sequential closed testing procedure was used to control Type I error rate across the primary and key secondary endpoints.
Method ANCOVA
Comments with treatment group (all treatment groups included) as fixed effect and baseline value as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.72
Confidence Interval (2-Sided) 95%
-0.92 to -0.53
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0990
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 10mg Dapagliflozin, Placebo
Comments The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0 (with alpha = 0.015 applying Dunnett's adjustment, two-sided)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments significant at alpha=0.015 (2-sided) applying Dunnett's adjustment. A sequential closed testing procedure was used to control Type I error rate across the primary and key secondary endpoints.
Method ANCOVA
Comments with treatment group (all treatment groups included) as fixed effect and baseline value as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.79
Confidence Interval (2-Sided) 95%
-0.99 to -0.59
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.1018
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Adjusted Mean Change in Fasting Plasma Glucose
Hide Description Change in fasting plasma glucose from baseline to Week 12 or the last post-baseline measurement prior to Week 12, if no Week 12 assessment is available.
Time Frame Baseline to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set, participants with non-missing baseline and Week 12 (LOCF) values
Arm/Group Title 1mg Dapagliflozin 2.5mg Dapagliflozin 5mg Dapagliflozin 10mg Dapagliflozin Placebo
Hide Arm/Group Description:
Dapagliflozin tablet 1 mg once daily
Dapagliflozin tablet 2.5 mg once daily
Dapagliflozin tablet 5 mg once daily
Dapagliflozin tablet 10 mg once daily
Placebo Comparator
Overall Number of Participants Analyzed 50 52 51 47 50
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mg/dL
-16.63
(-23.25 to -10.00)
-19.97
(-26.47 to -13.47)
-23.49
(-30.06 to -16.93)
-31.92
(-38.76 to -25.09)
9.45
(2.82 to 16.08)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1mg Dapagliflozin, Placebo
Comments The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus 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). Primary and key secondary endpoints are tested following a sequential closed testing procedure within treatment group.
Method ANCOVA
Comments with treatment group (all treatment groups included) as fixed effect and baseline value as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -26.08
Confidence Interval (2-Sided) 95%
-35.45 to -16.70
Parameter Dispersion
Type: Standard Error of the mean
Value: 4.7589
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 2.5mg Dapagliflozin, Placebo
Comments The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus 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). Primary and key secondary endpoints are tested following a sequential closed testing procedure within treatment group.
Method ANCOVA
Comments with treatment group (all treatment groups included) as fixed effect and baseline value as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -29.42
Confidence Interval (2-Sided) 95%
-38.70 to -20.14
Parameter Dispersion
Type: Standard Error of the mean
Value: 4.7100
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 5mg Dapagliflozin, Placebo
Comments The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus 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). Primary and key secondary endpoints are tested following a sequential closed testing procedure within treatment group.
Method ANCOVA
Comments with treatment group (all treatment groups included) as fixed effect and baseline value as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -32.94
Confidence Interval (2-Sided) 95%
-42.28 to -23.60
Parameter Dispersion
Type: Standard Error of the mean
Value: 4.7402
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 10mg Dapagliflozin, Placebo
Comments The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus 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). Primary and key secondary endpoints are tested following a sequential closed testing procedure within treatment group.
Method ANCOVA
Comments with treatment group (all treatment groups included) as fixed effect and baseline value as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -41.37
Confidence Interval (2-Sided) 95%
-50.90 to -31.85
Parameter Dispersion
Type: Standard Error of the mean
Value: 4.8358
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Proportion of Participants Achieving Glycemic Response Defined as HbA1c <7%
Hide Description Proportion of participants achieving therapeutic glycemic response defined as glycosylated hemoglobin <7%, after 12 weeks of double-blind therapy
Time Frame At Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set, participants with non-missing baseline and week 12 (LOCF) values
Arm/Group Title 1mg Dapagliflozin 2.5mg Dapagliflozin 5mg Dapagliflozin 10mg Dapagliflozin Placebo
Hide Arm/Group Description:
Dapagliflozin tablet 1 mg once daily
Dapagliflozin tablet 2.5 mg once daily
Dapagliflozin tablet 5 mg once daily
Dapagliflozin tablet 10 mg once daily
Placebo Comparator
Overall Number of Participants Analyzed 59 54 58 52 52
Measure Type: Number
Unit of Measure: Percentage of participants
1.7 9.3 5.2 9.6 1.9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1mg Dapagliflozin, Placebo
Comments H0: proportion(treat) minus proportion(placebo) = 0 versus HA: proportion(treat) minus proportion(placebo) =/= 0
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments not significant at alpha=0.05 (2-sided). Primary and key secondary endpoints are tested following a sequential closed testing procedure within treatment group.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-9.1 to 7.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 2.5mg Dapagliflozin, Placebo
Comments H0: proportion(treat) minus proportion(placebo) = 0 versus HA: proportion(treat) minus proportion(placebo) =/= 0
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2057
Comments not significant at alpha=0.05 (2-sided). Primary and key secondary endpoints are tested following a sequential closed testing procedure within treatment group.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 7.3
Confidence Interval (2-Sided) 95%
-2.3 to 18.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 5mg Dapagliflozin, Placebo
Comments H0: proportion(treat) minus proportion(placebo) = 0 versus HA: proportion(treat) minus proportion(placebo) =/= 0
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6203
Comments not significant at alpha=0.05 (2-sided). Primary and key secondary endpoints are tested following a sequential closed testing procedure within treatment group.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 3.2
Confidence Interval (2-Sided) 95%
-6.2 to 13.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 10mg Dapagliflozin, Placebo
Comments H0: proportion(treat) minus proportion(placebo) = 0 versus HA: proportion(treat) minus proportion(placebo) =/= 0
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2050
Comments not significant at alpha=0.05 (2-sided). Primary and key secondary endpoints are tested following a sequential closed testing procedure within treatment group.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 7.7
Confidence Interval (2-Sided) 95%
-2.0 to 19.5
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 12-week double-blind treatment plus 4/30 days or up to the follow-up visit 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 the study visit was assessed in comparison to the status at study entry.
 
Arm/Group Title 1mg Dapagliflozin 2.5mg Dapagliflozin 5mg Dapagliflozin 10mg Dapagliflozin Placebo
Hide Arm/Group Description Dapagliflozin tablet 1 mg once daily Dapagliflozin tablet 2.5 mg once daily Dapagliflozin tablet 5 mg once daily Dapagliflozin tablet 10 mg once daily Placebo Comparator
All-Cause Mortality
1mg Dapagliflozin 2.5mg Dapagliflozin 5mg Dapagliflozin 10mg Dapagliflozin Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
1mg Dapagliflozin 2.5mg Dapagliflozin 5mg Dapagliflozin 10mg Dapagliflozin Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/59 (3.39%)   1/56 (1.79%)   2/58 (3.45%)   1/52 (1.92%)   0/54 (0.00%) 
Cardiac disorders           
ACUTE MYOCARDIAL INFARCTION  1  0/59 (0.00%)  0/56 (0.00%)  1/58 (1.72%)  0/52 (0.00%)  0/54 (0.00%) 
General disorders           
MULTI-ORGAN FAILURE  1  1/59 (1.69%)  0/56 (0.00%)  0/58 (0.00%)  0/52 (0.00%)  0/54 (0.00%) 
Hepatobiliary disorders           
CHOLECYSTITIS  1  1/59 (1.69%)  0/56 (0.00%)  0/58 (0.00%)  0/52 (0.00%)  0/54 (0.00%) 
Infections and infestations           
GASTROENTERITIS  1  0/59 (0.00%)  0/56 (0.00%)  0/58 (0.00%)  1/52 (1.92%)  0/54 (0.00%) 
SEPSIS  1  1/59 (1.69%)  0/56 (0.00%)  0/58 (0.00%)  0/52 (0.00%)  0/54 (0.00%) 
Injury, poisoning and procedural complications           
SPINAL COMPRESSION FRACTURE  1  1/59 (1.69%)  0/56 (0.00%)  0/58 (0.00%)  0/52 (0.00%)  0/54 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
BLADDER CANCER  1  0/59 (0.00%)  1/56 (1.79%)  0/58 (0.00%)  0/52 (0.00%)  0/54 (0.00%) 
Skin and subcutaneous tissue disorders           
DERMAL CYST  1  0/59 (0.00%)  0/56 (0.00%)  1/58 (1.72%)  0/52 (0.00%)  0/54 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
1mg Dapagliflozin 2.5mg Dapagliflozin 5mg Dapagliflozin 10mg Dapagliflozin Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   14/59 (23.73%)   13/56 (23.21%)   14/58 (24.14%)   13/52 (25.00%)   14/54 (25.93%) 
Gastrointestinal disorders           
Constipation  1  3/59 (5.08%)  0/56 (0.00%)  2/58 (3.45%)  0/52 (0.00%)  1/54 (1.85%) 
Infections and infestations           
Nasopharyngitis  1  12/59 (20.34%)  10/56 (17.86%)  7/58 (12.07%)  12/52 (23.08%)  13/54 (24.07%) 
Nervous system disorders           
Headache  1  0/59 (0.00%)  3/56 (5.36%)  2/58 (3.45%)  1/52 (1.92%)  0/54 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Upper Respiratory Tract Inflammation  1  1/59 (1.69%)  0/56 (0.00%)  3/58 (5.17%)  0/52 (0.00%)  0/54 (0.00%) 
Skin and subcutaneous tissue disorders           
Eczema  1  0/59 (0.00%)  0/56 (0.00%)  0/58 (0.00%)  0/52 (0.00%)  3/54 (5.56%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.0
If an efficacy measurement was unavailable at the time point for analysis, last observation was carried forward (LOCF).
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: NCT00972244    
Other Study ID Numbers: D1692C00005
First Submitted: August 31, 2009
First Posted: September 4, 2009
Results First Submitted: January 21, 2013
Results First Posted: October 14, 2013
Last Update Posted: October 14, 2013