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A Study to Evaluate the Effect of Dapagliflozin With and Without Saxagliptin on Albuminuria, and to Investigate the Effect of Dapagliflozin and Saxagliptin on HbA1c in Patients With Type 2 Diabetes and CKD

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ClinicalTrials.gov Identifier: NCT02547935
Recruitment Status : Completed
First Posted : September 14, 2015
Results First Posted : June 4, 2019
Last Update Posted : August 21, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Type 2 Diabetes Mellitus, CKD and Albuminuria
Interventions Drug: Dapagliflozin 10 mg
Drug: Saxagliptin 2.5 mg
Drug: Matching Placebo for Dapagliflozin 10 mg and Saxagliptin 2.5mg
Enrollment 459
Recruitment Details Patients with Chronic Kidney Disease and Type 2 Diabetes Mellitus with micro- or macro-albuminuria and treated with ACEi or ARB were enrolled into an international, multi-centre study from 21 Sep 2015. The last patient's last visit was 18 May 2018.
Pre-assignment Details Enrolled patients were screened during a 4-week single-blind placebo lead-in period. Patients who met all of the inclusion and none of the exclusion criteria in this period were eligible to be randomised into the 24-week double-blind placebo-controlled treatment period.
Arm/Group Title Dapagliflozin 10 mg + Saxagliptin 2.5 mg Dapagliflozin 10 mg Placebo
Hide Arm/Group Description Dapagliflozin 10 milligram (mg) and saxagliptin 2.5 mg tablets were taken orally, once daily (in the morning) for 24 weeks. Dapagliflozin 10 mg tablets were taken orally, once daily (in the morning) for 24 weeks. Patients also took placebo tablets to match saxagliptin. Placebo tablets to match both active products (dapagliflozin and saxagliptin) were taken orally, once daily (in the morning) for 24 weeks.
Period Title: Overall Study
Started [1] 155 145 148
Received Treatment 152 145 148
Full Analysis Set 152 144 148
Safety Analysis Set 152 145 148
Completed 150 137 143
Not Completed 5 8 5
Reason Not Completed
Not specified             0             1             0
Withdrawal by Subject             2             3             4
Screen Failure             2             0             0
Physician Decision             0             1             0
Lost to Follow-up             0             2             1
Death             1             1             0
[1]
Patients randomised to 24-week double-blind treatment period.
Arm/Group Title Dapagliflozin 10 mg + Saxagliptin 2.5 mg Dapagliflozin 10 mg Placebo Total
Hide Arm/Group Description Dapagliflozin 10 mg and saxagliptin 2.5 mg tablets were taken orally, once daily (in the morning) for 24 weeks. Dapagliflozin 10 mg tablets were taken orally, once daily (in the morning) for 24 weeks. Patients also took placebo tablets to match saxagliptin. Placebo tablets to match both active products (dapagliflozin and saxagliptin) were taken orally, once daily (in the morning) for 24 weeks. Total of all reporting groups
Overall Number of Baseline Participants 155 145 148 448
Hide Baseline Analysis Population Description
Baseline characteristics are presented for all randomised patients.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 155 participants 145 participants 148 participants 448 participants
64.0  (9.21) 64.7  (8.61) 64.7  (8.53) 64.4  (8.78)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 155 participants 145 participants 148 participants 448 participants
<65 years
78
  50.3%
64
  44.1%
68
  45.9%
210
  46.9%
>=65 years
77
  49.7%
81
  55.9%
80
  54.1%
238
  53.1%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 155 participants 145 participants 148 participants 448 participants
Female
45
  29.0%
43
  29.7%
43
  29.1%
131
  29.2%
Male
110
  71.0%
102
  70.3%
105
  70.9%
317
  70.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 155 participants 145 participants 148 participants 448 participants
Hispanic or Latino
42
  27.1%
32
  22.1%
38
  25.7%
112
  25.0%
Not Hispanic or Latino
113
  72.9%
113
  77.9%
110
  74.3%
336
  75.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 155 participants 145 participants 148 participants 448 participants
White
77
  49.7%
55
  37.9%
64
  43.2%
196
  43.8%
Black or African American
8
   5.2%
7
   4.8%
11
   7.4%
26
   5.8%
Asian
57
  36.8%
67
  46.2%
53
  35.8%
177
  39.5%
Native Hawaiian or other Pacific Islander
1
   0.6%
2
   1.4%
1
   0.7%
4
   0.9%
American Indian or Alaska Native
0
   0.0%
1
   0.7%
1
   0.7%
2
   0.4%
Other
12
   7.7%
13
   9.0%
18
  12.2%
43
   9.6%
1.Primary Outcome
Title Adjusted Mean Change From Baseline in Glycosylated Haemoglobin (HbA1c): Comparison of Dapagliflozin 10 mg Plus Saxagliptin 2.5 mg and Placebo at Week 24
Hide Description HbA1c was analysed at baseline and every 4 weeks during the 24-week treatment period. Only measurements prior to rescue or treatment discontinuation were analysed. The adjusted mean change from baseline at Week 24 was analysed using a mixed model repeated measures (MMRM) model.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Patients from the Full Analysis Set (all randomised patients who took at least 1 dose of double-blind study drug and had a non missing baseline value and at least one post-baseline efficacy variable value) with non-missing baseline and Week 24 values for HbA1c.
Arm/Group Title Dapagliflozin 10 mg + Saxagliptin 2.5 mg Placebo
Hide Arm/Group Description:
Dapagliflozin 10 mg and saxagliptin 2.5 mg tablets were taken orally, once daily (in the morning) for 24 weeks.
Placebo tablets to match both active products (dapagliflozin and saxagliptin) were taken orally, once daily (in the morning) for 24 weeks.
Overall Number of Participants Analyzed 151 145
Least Squares Mean (Standard Error)
Unit of Measure: Percentage of Glycoslyated HbA1c
-0.85  (0.09) -0.27  (0.09)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dapagliflozin 10 mg + Saxagliptin 2.5 mg, Placebo
Comments A longitudinal repeated measures analysis included the fixed categorical effects of treatment, week, randomisation stratification factor (i.e. anti-diabetic treatment strata), and treatment-by-week interaction, as well as the continuous fixed covariates of baseline measurement and baseline measurement-by-week interaction.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Statistical significance level = 0.025.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in adjusted mean change
Estimated Value -0.58
Confidence Interval (2-Sided) 95%
-0.80 to -0.37
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.11
Estimation Comments [Not Specified]
2.Primary Outcome
Title Adjusted Mean Percent Change From Baseline in Urine Albumin-to-Creatinine Ratio (UACR) at Week 24
Hide Description UACR was analysed at baseline and every 4 weeks during the 24-week treatment period. All measurements regardless of rescue medication or treatment discontinuation were analysed. UACR values were first transformed to logarithms and the results were based on exponentiation of model estimates and expressed as adjusted mean percent change from baseline at Week 24.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Patients from the Full Analysis Set with non-missing baseline and Week 24 values for UACR.
Arm/Group Title Dapagliflozin 10 mg + Saxagliptin 2.5 mg Dapagliflozin 10 mg Placebo
Hide Arm/Group Description:
Dapagliflozin 10 mg and saxagliptin 2.5 mg tablets were taken orally, once daily (in the morning) for 24 weeks.
Dapagliflozin 10 mg tablets were taken orally, once daily (in the morning) for 24 weeks. Patients also took placebo tablets to match saxagliptin.
Placebo tablets to match both active products (dapagliflozin and saxagliptin) were taken orally, once daily (in the morning) for 24 weeks.
Overall Number of Participants Analyzed 151 140 144
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
-39.1  (5.1) -22.4  (6.6) -1.8  (8.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dapagliflozin 10 mg + Saxagliptin 2.5 mg, Placebo
Comments A longitudinal repeated measures model of the logarithms of the post-baseline to baseline ratios included the fixed categorical effects of treatment, week, treatment-by-week interaction, and randomisation stratification factor (i.e. anti-diabetic treatment strata), as well as the continuous fixed covariates of log-baseline UACR value and log-baseline UACR value-by-week interaction.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Statistical significance level = 0.025.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in adjusted mean change
Estimated Value -38.0
Confidence Interval (2-Sided) 95%
-48.2 to -25.8
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.7
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dapagliflozin 10 mg, Placebo
Comments A longitudinal repeated measures model of the logarithms of the post-baseline to baseline ratios included the fixed categorical effects of treatment, week, treatment-by-week interaction, and randomisation stratification factor (i.e. anti-diabetic treatment strata), as well as the continuous fixed covariates of log-baseline UACR value and log-baseline UACR value-by-week interaction.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.011
Comments Statistical significance level = 0.025.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in adjusted mean change
Estimated Value -21.0
Confidence Interval (2-Sided) 95%
-34.1 to -5.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 7.3
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Adjusted Mean Percent Change From Baseline in Total Body Weight at Week 24
Hide Description Total body weight was measured in kilograms (kg) at baseline and at Week 1 then every 4 weeks during the 24-week treatment period. All measurements regardless of rescue medication or treatment discontinuation were analysed. Total body weight values were first transformed to logarithms and the results were based on exponentiation of model estimates and expressed as adjusted mean percent change from baseline at Week 24.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Patients from the Full Analysis Set with non-missing baseline and Week 24 values for total body weight.
Arm/Group Title Dapagliflozin 10 mg + Saxagliptin 2.5 mg Dapagliflozin 10 mg Placebo
Hide Arm/Group Description:
Dapagliflozin 10 mg and saxagliptin 2.5 mg tablets were taken orally, once daily (in the morning) for 24 weeks.
Dapagliflozin 10 mg tablets were taken orally, once daily (in the morning) for 24 weeks. Patients also took placebo tablets to match saxagliptin.
Placebo tablets to match both active products (dapagliflozin and saxagliptin) were taken orally, once daily (in the morning) for 24 weeks.
Overall Number of Participants Analyzed 152 144 148
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
-0.65  (0.55) -1.48  (0.56) -0.61  (0.56)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dapagliflozin 10 mg + Saxagliptin 2.5 mg, Placebo
Comments A longitudinal repeated measures model of the logarithms of the post-baseline to baseline ratios included the fixed categorical effects of treatment, week, treatment-by-week interaction, and randomisation stratification factor (i.e. anti-diabetic treatment strata), as well as the continuous fixed covariates of log-baseline total body weight value and log-baseline total body weight value-by-week interaction.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.953
Comments Statistical significance level = 0.025.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in adjusted mean change
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-1.32 to 1.26
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.66
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dapagliflozin 10 mg, Placebo
Comments A longitudinal repeated measures model of the logarithms of the post-baseline to baseline ratios included the fixed categorical effects of treatment, week, treatment-by-week interaction, and randomisation stratification factor (i.e. anti-diabetic treatment strata), as well as the continuous fixed covariates of log-baseline total body weight value and log-baseline total body weight value-by-week interaction.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.193
Comments Statistical significance level = 0.025.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in adjusted mean change
Estimated Value -0.87
Confidence Interval (2-Sided) 95%
-2.17 to 0.44
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.66
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
Hide Description FPG was analysed at baseline and Week 1 then every 4 weeks during the 24-week treatment period. Only measurements prior to rescue or treatment discontinuation were analysed. The adjusted mean change from baseline at Week 24 was analysed using a MMRM model.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Patients from the Full Analysis Set with non-missing baseline and Week 24 values for FPG.
Arm/Group Title Dapagliflozin 10 mg + Saxagliptin 2.5 mg Dapagliflozin 10 mg Placebo
Hide Arm/Group Description:
Dapagliflozin 10 mg and saxagliptin 2.5 mg tablets were taken orally, once daily (in the morning) for 24 weeks.
Dapagliflozin 10 mg tablets were taken orally, once daily (in the morning) for 24 weeks. Patients also took placebo tablets to match saxagliptin.
Placebo tablets to match both active products (dapagliflozin and saxagliptin) were taken orally, once daily (in the morning) for 24 weeks.
Overall Number of Participants Analyzed 152 144 147
Least Squares Mean (Standard Error)
Unit of Measure: mg/decilitre (dL)
-17.2  (5.2) -13.1  (5.4) -11.2  (5.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dapagliflozin 10 mg + Saxagliptin 2.5 mg, Placebo
Comments A longitudinal repeated measures analysis included the fixed categorical effects of treatment, week, randomisation stratification factor (i.e.anti-diabetic treatment strata), and treatment-by-week interaction, as well as the continuous fixed covariates of baseline measurement and baseline measurement-by-week interaction.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.298
Comments Statistical significance level = 0.025.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in adjusted mean change
Estimated Value -6.1
Confidence Interval (2-Sided) 95%
-17.5 to 5.4
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.8
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dapagliflozin 10 mg, Placebo
Comments A longitudinal repeated measures analysis included the fixed categorical effects of treatment, week, randomisation stratification factor (i.e.anti-diabetic treatment strata), and treatment-by-week interaction, as well as the continuous fixed covariates of baseline measurement and baseline measurement-by-week interaction.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.746
Comments Statistical significance level = 0.025.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in adjusted mean change
Estimated Value -1.9
Confidence Interval (2-Sided) 95%
-13.6 to 9.8
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.9
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Patients Achieving at Least 30% Reduction in UACR at Week 24
Hide Description The percentage of patients meeting the criteria of at least a 30% reduction in UACR, was analysed using a logistic regression model. If no measurement was available at Week 24 the last available post-baseline measurement was carried forward (Last Observation Carried Forward [LOCF]).
Time Frame From baseline up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Patients from the Full Analysis Set with non-missing baseline and at least one post-baseline UACR value.
Arm/Group Title Dapagliflozin 10 mg + Saxagliptin 2.5 mg Dapagliflozin 10 mg Placebo
Hide Arm/Group Description:
Dapagliflozin 10 mg and saxagliptin 2.5 mg tablets were taken orally, once daily (in the morning) for 24 weeks.
Dapagliflozin 10 mg tablets were taken orally, once daily (in the morning) for 24 weeks. Patients also took placebo tablets to match saxagliptin.
Placebo tablets to match both active products (dapagliflozin and saxagliptin) were taken orally, once daily (in the morning) for 24 weeks.
Overall Number of Participants Analyzed 152 144 148
Measure Type: Number
Unit of Measure: Percentage of patients
57.0 45.0 31.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dapagliflozin 10 mg + Saxagliptin 2.5 mg, Placebo
Comments Logistic regression model analysis with adjustment for baseline UACR and pooled randomisation strata.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Statistical significance level = 0.025.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.98
Confidence Interval (2-Sided) 95%
1.8 to 4.8
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dapagliflozin 10 mg, Placebo
Comments Logistic regression model analysis with adjustment for baseline UACR and pooled randomisation strata.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.013
Comments Statistical significance level = 0.025.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.86
Confidence Interval (2-Sided) 95%
1.1 to 3.0
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Patients Achieving a Reduction in HbA1c of Less Than 7.0% at Week 24
Hide Description The percentage of patients meeting the criteria of a less than 7% reduction in HbA1c, was analysed using a logistic regression model. If no measurement was available at Week 24 the last available post-baseline measurement was carried forward (LOCF). Only measurements prior to rescue or treatment discontinuation were analysed.
Time Frame From baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Patients from the Full Analysis Set with non-missing baseline and at least one post-baseline HbA1c value.
Arm/Group Title Dapagliflozin 10 mg + Saxagliptin 2.5 mg Dapagliflozin 10 mg Placebo
Hide Arm/Group Description:
Dapagliflozin 10 mg and saxagliptin 2.5 mg tablets were taken orally, once daily (in the morning) for 24 weeks.
Dapagliflozin 10 mg tablets were taken orally, once daily (in the morning) for 24 weeks. Patients also took placebo tablets to match saxagliptin.
Placebo tablets to match both active products (dapagliflozin and saxagliptin) were taken orally, once daily (in the morning) for 24 weeks.
Overall Number of Participants Analyzed 152 144 148
Measure Type: Number
Unit of Measure: Percentage of patients
35.1 15.0 10.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dapagliflozin 10 mg + Saxagliptin 2.5 mg, Placebo
Comments Logistic regression model analysis with adjustment for baseline HbA1c and pooled randomisation strata.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Statistical significance level = 0.025.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.43
Confidence Interval (2-Sided) 95%
2.6 to 11.2
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dapagliflozin 10 mg, Placebo
Comments Logistic regression model analysis with adjustment for baseline HbA1c and pooled randomisation strata.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.167
Comments Statistical significance level = 0.025.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.74
Confidence Interval (2-Sided) 95%
0.8 to 3.8
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Adjusted Mean Change From Baseline in Seated Systolic Blood Pressure (SBP) at Week 24
Hide Description Seated SBP was analysed at baseline, Week 1 and every 4 weeks during the 24-week treatment period. All measurements regardless of rescue medication or treatment discontinuation were analysed. The adjusted mean change from baseline at Week 24 was analysed using a MMRM model.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Patients from the Full Analysis Set with non-missing baseline and Week 24 values for SBP.
Arm/Group Title Dapagliflozin 10 mg + Saxagliptin 2.5 mg Dapagliflozin 10 mg Placebo
Hide Arm/Group Description:
Dapagliflozin 10 mg and saxagliptin 2.5 mg tablets were taken orally, once daily (in the morning) for 24 weeks.
Dapagliflozin 10 mg tablets were taken orally, once daily (in the morning) for 24 weeks. Patients also took placebo tablets to match saxagliptin.
Placebo tablets to match both active products (dapagliflozin and saxagliptin) were taken orally, once daily (in the morning) for 24 weeks.
Overall Number of Participants Analyzed 152 144 147
Least Squares Mean (Standard Error)
Unit of Measure: Millimetre of mercury (mmHg)
-8.8  (1.6) -6.9  (1.7) -4.1  (1.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dapagliflozin 10 mg + Saxagliptin 2.5 mg, Placebo
Comments A longitudinal repeated measures model of the logarithms of the post-baseline to baseline ratios, included the fixed categorical effects of treatment, week, treatment-by-week interaction, and randomisation strata, as well as the continuous fixed covariates of log-baseline SBP value and log-baseline SBP value-by-week interaction.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.009
Comments Statistical significance level = 0.025.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in adjusted mean change
Estimated Value -4.8
Confidence Interval (2-Sided) 95%
-8.3 to -1.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.8
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dapagliflozin 10 mg, Placebo
Comments A longitudinal repeated measures model of the logarithms of the post-baseline to baseline ratios, included the fixed categorical effects of treatment, week, treatment-by-week interaction, and randomisation strata, as well as the continuous fixed covariates of log-baseline SBP value and log-baseline SBP value-by-week interaction.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.122
Comments Statistical significance level = 0.025.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in adjusted mean change
Estimated Value -2.8
Confidence Interval (2-Sided) 95%
-6.4 to 0.8
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.8
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Adjusted Mean Change From Baseline in HbA1c: Comparison of Dapagliflozin 10 mg and Placebo at Week 24
Hide Description HbA1c was analysed at baseline and every 4 weeks during the 24-week treatment period. Only measurements prior to rescue or treatment discontinuation were analysed. The adjusted mean change from baseline at Week 24 was analysed using a MMRM model.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Patients from the Full Analysis Set with non-missing baseline and Week 24 values for HbA1c.
Arm/Group Title Dapagliflozin 10 mg Placebo
Hide Arm/Group Description:
Dapagliflozin 10 mg tablets were taken orally, once daily (in the morning) for 24 weeks. Patients also took placebo tablets to match saxagliptin.
Placebo tablets to match both active products (dapagliflozin and saxagliptin) were taken orally, once daily (in the morning) for 24 weeks.
Overall Number of Participants Analyzed 140 145
Least Squares Mean (Standard Error)
Unit of Measure: Percentage of Glycoslyated HbA1c
-0.43  (0.09) -0.27  (0.09)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dapagliflozin 10 mg, Placebo
Comments A longitudinal repeated measures analysis included the fixed categorical effects of treatment, week, randomisation stratification factor (i.e. anti-diabetic treatment strata), and treatment-by-week interaction, as well as the continuous fixed covariates of baseline measurement and baseline measurement-by-week interaction.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.142
Comments Statistical significance level = 0.025.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in adjusted mean change
Estimated Value -0.16
Confidence Interval (2-Sided) 95%
-0.38 to 0.05
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.11
Estimation Comments [Not Specified]
Time Frame Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks.
Adverse Event Reporting Description The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
 
Arm/Group Title Dapagliflozin 10 mg + Saxagliptin 2.5 mg Dapagliflozin 10 mg Placebo
Hide Arm/Group Description Dapagliflozin 10 mg and saxagliptin 2.5 mg tablets were taken orally, once daily (in the morning) for 24 weeks. Dapagliflozin 10 mg tablets were taken orally, once daily (in the morning) for 24 weeks. Patients also took placebo tablets to match saxagliptin. Placebo tablets to match both active products (dapagliflozin and saxagliptin)were taken orally, once daily (in the morning) for 24 weeks.
All-Cause Mortality
Dapagliflozin 10 mg + Saxagliptin 2.5 mg Dapagliflozin 10 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/152 (0.66%)      1/145 (0.69%)      0/148 (0.00%)    
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Dapagliflozin 10 mg + Saxagliptin 2.5 mg Dapagliflozin 10 mg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   12/152 (7.89%)      12/145 (8.28%)      16/148 (10.81%)    
Blood and lymphatic system disorders       
Anaemia  1  0/152 (0.00%)  0 0/145 (0.00%)  0 1/148 (0.68%)  1
Iron deficiency anaemia  1  1/152 (0.66%)  1 0/145 (0.00%)  0 0/148 (0.00%)  0
Splenomegaly  1  0/152 (0.00%)  0 0/145 (0.00%)  0 1/148 (0.68%)  1
Cardiac disorders       
Angina pectoris  1  0/152 (0.00%)  0 1/145 (0.69%)  1 2/148 (1.35%)  2
Atrial fibrillation  1  1/152 (0.66%)  1 0/145 (0.00%)  0 0/148 (0.00%)  0
Cardiac failure  1  0/152 (0.00%)  0 1/145 (0.69%)  1 0/148 (0.00%)  0
Cardiogenic shock  1  1/152 (0.66%)  1 0/145 (0.00%)  0 0/148 (0.00%)  0
Myocardial infarction  1  0/152 (0.00%)  0 0/145 (0.00%)  0 2/148 (1.35%)  2
Ventricular extrasystoles  1  0/152 (0.00%)  0 1/145 (0.69%)  1 0/148 (0.00%)  0
Ear and labyrinth disorders       
Vertigo  1  0/152 (0.00%)  0 0/145 (0.00%)  0 1/148 (0.68%)  1
Gastrointestinal disorders       
Diarrhoea  1  0/152 (0.00%)  0 1/145 (0.69%)  1 0/148 (0.00%)  0
Duodenal ulcer haemorrhage  1  1/152 (0.66%)  1 0/145 (0.00%)  0 0/148 (0.00%)  0
General disorders       
Chest pain  1  1/152 (0.66%)  1 0/145 (0.00%)  0 0/148 (0.00%)  0
Pyrexia  1  0/152 (0.00%)  0 0/145 (0.00%)  0 1/148 (0.68%)  1
Hepatobiliary disorders       
Bile duct stone  1  0/152 (0.00%)  0 1/145 (0.69%)  1 0/148 (0.00%)  0
Infections and infestations       
Diabetic foot infection  1  1/152 (0.66%)  1 0/145 (0.00%)  0 0/148 (0.00%)  0
Emphysematous pyelonephritis  1  1/152 (0.66%)  1 0/145 (0.00%)  0 0/148 (0.00%)  0
Genital infection  1  0/152 (0.00%)  0 1/145 (0.69%)  1 0/148 (0.00%)  0
Groin abscess  1  1/152 (0.66%)  1 0/145 (0.00%)  0 0/148 (0.00%)  0
Pneumonia influenzal  1  0/152 (0.00%)  0 1/145 (0.69%)  1 0/148 (0.00%)  0
Upper respiratory tract infection  1  0/152 (0.00%)  0 0/145 (0.00%)  0 1/148 (0.68%)  1
Urinary tract infection  1  0/152 (0.00%)  0 0/145 (0.00%)  0 1/148 (0.68%)  1
Injury, poisoning and procedural complications       
Ankle fracture  1  0/152 (0.00%)  0 0/145 (0.00%)  0 2/148 (1.35%)  2
Humerus fracture  1  0/152 (0.00%)  0 1/145 (0.69%)  1 0/148 (0.00%)  0
Metabolism and nutrition disorders       
Hyperkalaemia  1  0/152 (0.00%)  0 1/145 (0.69%)  1 0/148 (0.00%)  0
Hypoglycaemia  1  2/152 (1.32%)  2 0/145 (0.00%)  0 1/148 (0.68%)  1
Musculoskeletal and connective tissue disorders       
Spinal osteoarthritis  1  0/152 (0.00%)  0 1/145 (0.69%)  1 0/148 (0.00%)  0
Nervous system disorders       
Cerebrovascular accident  1  0/152 (0.00%)  0 0/145 (0.00%)  0 2/148 (1.35%)  3
Dizziness  1  0/152 (0.00%)  0 1/145 (0.69%)  1 0/148 (0.00%)  0
Headache  1  0/152 (0.00%)  0 0/145 (0.00%)  0 1/148 (0.68%)  1
Presyncope  1  0/152 (0.00%)  0 0/145 (0.00%)  0 1/148 (0.68%)  1
Syncope  1  0/152 (0.00%)  0 2/145 (1.38%)  2 0/148 (0.00%)  0
Transient ischaemic attack  1  1/152 (0.66%)  1 0/145 (0.00%)  0 0/148 (0.00%)  0
Renal and urinary disorders       
Acute kidney injury  1  0/152 (0.00%)  0 0/145 (0.00%)  0 2/148 (1.35%)  2
Glomerulonephritis rapidly progressive  1  0/152 (0.00%)  0 0/145 (0.00%)  0 1/148 (0.68%)  1
Urinary retention  1  0/152 (0.00%)  0 0/145 (0.00%)  0 1/148 (0.68%)  1
Respiratory, thoracic and mediastinal disorders       
Dyspnoea  1  1/152 (0.66%)  1 0/145 (0.00%)  0 0/148 (0.00%)  0
Respiratory failure  1  0/152 (0.00%)  0 1/145 (0.69%)  1 0/148 (0.00%)  0
Skin and subcutaneous tissue disorders       
Diabetic foot  1  1/152 (0.66%)  1 0/145 (0.00%)  0 0/148 (0.00%)  0
Vascular disorders       
Peripheral ischaemia  1  0/152 (0.00%)  0 0/145 (0.00%)  0 1/148 (0.68%)  1
1
Term from vocabulary, MedDRA 21.0
Indicates events were collected by systematic assessment
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Frequency Threshold for Reporting Other Adverse Events 5%
Dapagliflozin 10 mg + Saxagliptin 2.5 mg Dapagliflozin 10 mg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   12/152 (7.89%)      18/145 (12.41%)      8/148 (5.41%)    
Infections and infestations       
Influenza  1  2/152 (1.32%)  2 8/145 (5.52%)  8 2/148 (1.35%)  2
Nasopharyngitis  1  10/152 (6.58%)  12 10/145 (6.90%)  11 6/148 (4.05%)  6
1
Term from vocabulary, MedDRA 21.0
Indicates events were collected by systematic assessment
Anomalous data at 1 site was identified following completion of the study. All data from this site were excluded from the full analysis following an audit; the findings led the sponsor to believe the site did not comply with the principles of GCP.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
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Name/Title: Global Clinical Lead
Organization: AstraZeneca
Phone: +1 302 885 1180
EMail: ClinicalTrialTransparency@astrazeneca.com
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02547935     History of Changes
Other Study ID Numbers: D1690C00023
First Submitted: August 31, 2015
First Posted: September 14, 2015
Results First Submitted: May 15, 2019
Results First Posted: June 4, 2019
Last Update Posted: August 21, 2019