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Phase 3 28-Week Study With 24-Week and 52-week Extension Phases to Evaluate Efficacy and Safety of Exenatide Once Weekly and Dapagliflozin Versus Exenatide and Dapagliflozin Matching Placebo

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: NCT02229396
Recruitment Status : Completed
First Posted : September 1, 2014
Results First Posted : September 8, 2017
Last Update Posted : December 31, 2018
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 Diabetes Mellitus
Interventions Drug: Exantide with Dapagliflozin
Drug: Exentide
Drug: Dapagliflozin
Enrollment 695
Recruitment Details Study conducted between 04 September 2014 and 28 December 2017. 118 centers in 6 countries randomized patients in the study. A Primary Analysis was performed following completion of the 28-week Treatment Period with a data cut-off date of 26 April 2016. All Primary and Secondary Outcome measures were reported at the time of the Primary Analysis.
Pre-assignment Details The study had a Screening Visit, a 1-week placebo Lead-in Period, a Randomization Visit, and 9 further visits at 1- to 4-week intervals during a 28-week Treatment Period. Patients then entered a 24-week Extension Period 1 and subsequent 52-week Extension Period 2. A follow-up visit occurred 10 weeks after last dose of study medication.
Arm/Group Title Dapagliflozin + Placebo Exenatide + Dapagliflozin Exenatide + Placebo
Hide Arm/Group Description Dapagliflozin 10 milligram (mg) tablet administered orally once daily + matching placebo for exenatide administered as subcutaneous (SC) injection once weekly. Patients continued to administer the same type and dose of metformin therapy they were using at study entry. Exenatide once weekly (EQW) 2 mg administered as SC injection + dapagliflozin 10 mg tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry. Exenatide once weekly (EQW) 2 mg administered as SC injection + matching placebo for dapagliflozin tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.
Period Title: Overall Study
Started 233 231 231
Randomization Code Allocated 233 231 231
Safety Analysis Set 233 231 230
Intent-to-Treat (ITT) Analysis Set 230 228 227
Completed 28-Week Study Period 208 202 193
Completed 52-Week Study Period 194 193 177
Completed [1] 155 154 136
Not Completed 78 77 95
Reason Not Completed
Adverse Event             6             12             12
Death             2             3             1
Lost to Follow-up             14             14             21
Protocol Violation             2             1             0
Patient Incorrectly Randomized             0             0             1
Other             10             18             15
Withdrawal by Subject             42             28             41
Study-Specific Withdrawal Criteria             0             1             3
Withdrew; No Record on Termination Page             2             0             1
[1]
Completed 104-Week Study Period
Arm/Group Title Dapagliflozin + Placebo Exenatide + Dapagliflozin Exenatide + Placebo Total
Hide Arm/Group Description Dapagliflozin 10 mg tablet administered orally once daily + matching placebo for exenatide administered as SC injection once weekly. Patients continued to administer the same type and dose of metformin therapy they were using at study entry. Exenatide once weekly (EQW) 2 mg administered as SC injection + dapagliflozin 10 mg tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry. Exenatide once weekly (EQW) 2 mg administered as SC injection + matching placebo for dapagliflozin tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry. Total of all reporting groups
Overall Number of Baseline Participants 230 228 227 685
Hide Baseline Analysis Population Description
The overall number of baseline participants is comprised of the ITT analysis set, defined as all randomized patients who received at least 1 dose of study medication and had at least 1 post-baseline hemoglobin A1c (HbA1c) assessment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 230 participants 228 participants 227 participants 685 participants
54.5  (9.16) 53.8  (9.82) 54.2  (9.62) 54.2  (9.53)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 230 participants 228 participants 227 participants 685 participants
Female
120
  52.2%
126
  55.3%
111
  48.9%
357
  52.1%
Male
110
  47.8%
102
  44.7%
116
  51.1%
328
  47.9%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 230 participants 228 participants 227 participants 685 participants
American Indian Or Alaska Native 0 0 2 2
Asian 1 3 1 5
Black Or African American 33 34 27 94
Other 7 1 3 11
White 189 190 194 573
1.Primary Outcome
Title Change in HbA1c From Baseline to Week 28
Hide Description To compare the change from baseline to Week 28 in HbA1c between exenatide once weekly (EQW) 2 mg and dapagliflozin 10 mg administered simultaneously compared to EQW 2 mg alone and dapagliflozin 10 mg alone.
Time Frame Baseline to Week 28
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all randomized patients who received at least 1 dose of study medication and had at least 1 post-baseline HbA1c assessment.
Arm/Group Title Dapagliflozin + Placebo Exenatide + Dapagliflozin Exenatide + Placebo
Hide Arm/Group Description:
Dapagliflozin 10 mg tablet administered orally once daily + matching placebo for exenatide administered as SC injection once weekly. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.
Exenatide once weekly (EQW) 2 mg administered as SC injection + dapagliflozin 10 mg tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.
Exenatide once weekly (EQW) 2 mg administered as SC injection + matching placebo for dapagliflozin tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.
Overall Number of Participants Analyzed 230 228 227
Least Squares Mean (95% Confidence Interval)
Unit of Measure: % HbA1c
-1.39
(-1.57 to -1.21)
-1.98
(-2.16 to -1.79)
-1.60
(-1.79 to -1.41)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Exenatide + Dapagliflozin, Exenatide + Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method Mixed Models Analysis
Comments Treatment, region, baseline HbA1c stratum (<9.0% or ≥9.0%), week, and treatment by week interaction as fixed factors; baseline value as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.38
Confidence Interval (2-Sided) 95%
-0.63 to -0.13
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.129
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dapagliflozin + Placebo, Exenatide + Dapagliflozin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Treatment, region, baseline HbA1c stratum (<9.0% or ≥9.0%), week, and treatment by week interaction as fixed factors; baseline value as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.59
Confidence Interval (2-Sided) 95%
-0.84 to -0.34
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.127
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change in Body Weight From Baseline to Week 28
Hide Description To compare the change from baseline to Week 28 in body weight between exenatide once weekly (EQW) 2 mg and dapagliflozin 10 mg administered simultaneously compared to EQW 2 mg alone and dapagliflozin 10 mg alone.
Time Frame Baseline to Week 28
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all randomized patients who received at least 1 dose of study medication and had at least 1 post-baseline HbA1c assessment.
Arm/Group Title Dapagliflozin + Placebo Exenatide + Dapagliflozin Exenatide + Placebo
Hide Arm/Group Description:
Dapagliflozin 10 mg tablet administered orally once daily + matching placebo for exenatide administered as SC injection once weekly. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.
Exenatide once weekly (EQW) 2 mg administered as SC injection + dapagliflozin 10 mg tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.
Exenatide once weekly (EQW) 2 mg administered as SC injection + matching placebo for dapagliflozin tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.
Overall Number of Participants Analyzed 230 228 227
Least Squares Mean (95% Confidence Interval)
Unit of Measure: kilogram
-2.22
(-2.78 to -1.66)
-3.55
(-4.12 to -2.99)
-1.56
(-2.13 to -0.98)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Exenatide + Dapagliflozin, Exenatide + Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Treatment, region, baseline HbA1c stratum (<9.0% or ≥9.0%), week, and treatment by week interaction as fixed factors; baseline value as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.00
Confidence Interval (2-Sided) 95%
-2.79 to -1.20
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.406
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dapagliflozin + Placebo, Exenatide + Dapagliflozin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Treatment, region, baseline HbA1c stratum (<9.0% or ≥9.0%), week, and treatment by week interaction as fixed factors; baseline value as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.33
Confidence Interval (2-Sided) 95%
-2.12 to -0.55
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.400
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change in Fasting Plasma Glucose From Baseline to Week 28
Hide Description To compare the change from baseline to Week 28 in fasting plasma glucose between exenatide once weekly (EQW) 2 mg and dapagliflozin 10 mg administered simultaneously compared to EQW 2 mg alone and dapagliflozin 10 mg alone.
Time Frame Baseline to Week 28
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all randomized patients who received at least 1 dose of study medication and had at least 1 post-baseline HbA1c assessment.
Arm/Group Title Dapagliflozin + Placebo Exenatide + Dapagliflozin Exenatide + Placebo
Hide Arm/Group Description:
Dapagliflozin 10 mg tablet administered orally once daily + matching placebo for exenatide administered as SC injection once weekly. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.
Exenatide once weekly (EQW) 2 mg administered as SC injection + dapagliflozin 10 mg tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.
Exenatide once weekly (EQW) 2 mg administered as SC injection + matching placebo for dapagliflozin tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.
Overall Number of Participants Analyzed 230 228 227
Least Squares Mean (95% Confidence Interval)
Unit of Measure: milligrams/deciliter (mg/dL)
-49.19
(-54.91 to -43.47)
-65.83
(-71.60 to -60.06)
-45.75
(-51.67 to -39.83)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Exenatide + Dapagliflozin, Exenatide + Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Treatment, region, baseline HbA1c stratum (<9.0% or ≥9.0%), week, and treatment by week interaction as fixed factors; baseline value as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -20.08
Confidence Interval (2-Sided) 95%
-27.95 to -12.20
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.007
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dapagliflozin + Placebo, Exenatide + Dapagliflozin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Treatment, region, baseline HbA1c stratum (<9.0% or ≥9.0%), week, and treatment by week interaction as fixed factors; baseline value as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -16.64
Confidence Interval (2-Sided) 95%
-24.39 to -8.89
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.947
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline to Week 28 in 2-hour Postprandial Glucose After a Standard Meal Tolerance Test
Hide Description To compare the change from baseline to Week 28 in 2-hour postprandial glucose after a standard Meal Tolerance Test between exenatide once weekly (EQW) 2 mg and dapagliflozin 10 mg administered simultaneously compared to EQW 2 mg alone and dapagliflozin 10 mg alone.
Time Frame Baseline to Week 28
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all randomized patients who received at least 1 dose of study medication and had at least 1 post-baseline HbA1c assessment.
Arm/Group Title Dapagliflozin + Placebo Exenatide + Dapagliflozin Exenatide + Placebo
Hide Arm/Group Description:
Dapagliflozin 10 mg tablet administered orally once daily + matching placebo for exenatide administered as SC injection once weekly. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.
Exenatide once weekly (EQW) 2 mg administered as SC injection + dapagliflozin 10 mg tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.
Exenatide once weekly (EQW) 2 mg administered as SC injection + matching placebo for dapagliflozin tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.
Overall Number of Participants Analyzed 230 228 227
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mg/dL
-61.05
(-69.10 to -53.00)
-87.83
(-95.83 to -79.84)
-60.09
(-68.48 to -51.71)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Exenatide + Dapagliflozin, Exenatide + Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments Treatment, region, and baseline HbA1c stratum (<9.0% or ≥9.0%), as fixed factors; baseline value as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -27.74
Confidence Interval (2-Sided) 95%
-37.89 to -17.59
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.168
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dapagliflozin + Placebo, Exenatide + Dapagliflozin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments Treatment, region, and baseline HbA1c stratum (<9.0% or ≥9.0%), as fixed factors; baseline value as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -26.78
Confidence Interval (2-Sided) 95%
-36.78 to -16.78
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.090
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Patients Achieving Weight Loss ≥5.0% at Week 28
Hide Description To compare the percentage of patients achieving weight loss ≥5.0% at 28 weeks between exenatide once weekly (EQW) 2 mg and dapagliflozin 10 mg administered simultaneously compared to EQW 2 mg alone and dapagliflozin 10 mg alone.
Time Frame Baseline to Week 28
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all randomized patients who received at least 1 dose of study medication and had at least 1 post-baseline HbA1c assessment.
Arm/Group Title Dapagliflozin + Placebo Exenatide + Dapagliflozin Exenatide + Placebo
Hide Arm/Group Description:
Dapagliflozin 10 mg tablet administered orally once daily + matching placebo for exenatide administered as SC injection once weekly. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.
Exenatide once weekly (EQW) 2 mg administered as SC injection + dapagliflozin 10 mg tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.
Exenatide once weekly (EQW) 2 mg administered as SC injection + matching placebo for dapagliflozin tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.
Overall Number of Participants Analyzed 230 228 227
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: % of patients
20.0
(14.8 to 25.2)
33.3
(27.2 to 39.5)
13.7
(9.2 to 18.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Exenatide + Dapagliflozin, Exenatide + Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Stratified by baseline HbA1c (<9.0% or ≥9.0%).
Method of Estimation Estimation Parameter Difference in percentages
Estimated Value 19.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dapagliflozin + Placebo, Exenatide + Dapagliflozin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Stratified by baseline HbA1c (<9.0% or ≥9.0%).
Method of Estimation Estimation Parameter Difference in percentages
Estimated Value 13.3
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change in Fasting Plasma Glucose From Baseline to Week 2
Hide Description To compare the change from baseline to Week 2 in fasting plasma glucose between exenatide once weekly (EQW) 2 mg and dapagliflozin 10 mg administered simultaneously compared to EQW 2 mg alone and dapagliflozin 10 mg alone.
Time Frame Baseline to Week 2
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all randomized patients who received at least 1 dose of study medication and had at least 1 post-baseline HbA1c assessment.
Arm/Group Title Dapagliflozin + Placebo Exenatide + Dapagliflozin Exenatide + Placebo
Hide Arm/Group Description:
Dapagliflozin 10 mg tablet administered orally once daily + matching placebo for exenatide administered as SC injection once weekly. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.
Exenatide once weekly (EQW) 2 mg administered as SC injection + dapagliflozin 10 mg tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.
Exenatide once weekly (EQW) 2 mg administered as SC injection + matching placebo for dapagliflozin tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.
Overall Number of Participants Analyzed 230 228 227
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mg/dL
-26.31
(-31.42 to -21.20)
-41.34
(-46.48 to -36.20)
-21.08
(-26.29 to -15.86)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Exenatide + Dapagliflozin, Exenatide + Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Treatment, region, baseline HbA1c stratum (<9.0% or ≥9.0%), week, and treatment by week interaction as fixed factors; baseline value as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -20.26
Confidence Interval (2-Sided) 95%
-27.12 to -13.40
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.494
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dapagliflozin + Placebo, Exenatide + Dapagliflozin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments This is a nominal p-value.
Method Mixed Models Analysis
Comments Treatment, region, baseline HbA1c stratum (<9.0% or ≥9.0%), week, and treatment by week interaction as fixed factors; baseline value as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -15.03
Confidence Interval (2-Sided) 95%
-21.85 to -8.20
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.477
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Percentage of Patients Achieving HbA1c <7% at Week 28
Hide Description To compare the percentage of patients achieving HbA1c <7% at 28 weeks between exenatide once weekly (EQW) 2 mg and dapagliflozin 10 mg administered simultaneously compared to EQW 2 mg alone and dapagliflozin 10 mg alone.
Time Frame Baseline to Week 28
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all randomized patients who received at least 1 dose of study medication and had at least 1 post-baseline HbA1c assessment.
Arm/Group Title Dapagliflozin + Placebo Exenatide + Dapagliflozin Exenatide + Placebo
Hide Arm/Group Description:
Dapagliflozin 10 mg tablet administered orally once daily + matching placebo for exenatide administered as SC injection once weekly. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.
Exenatide once weekly (EQW) 2 mg administered as SC injection + dapagliflozin 10 mg tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.
Exenatide once weekly (EQW) 2 mg administered as SC injection + matching placebo for dapagliflozin tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.
Overall Number of Participants Analyzed 230 228 227
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: % of patients
19.1
(14.1 to 24.2)
44.7
(38.3 to 51.2)
26.9
(21.1 to 32.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Exenatide + Dapagliflozin, Exenatide + Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Stratified by baseline HbA1c (<9.0% or ≥9.0%).
Method of Estimation Estimation Parameter Difference in percentages
Estimated Value 17.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dapagliflozin + Placebo, Exenatide + Dapagliflozin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Stratified by baseline HbA1c (<9.0% or ≥9.0%).
Method of Estimation Estimation Parameter Difference in percentages
Estimated Value 25.6
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change in Systolic Blood Pressure From Baseline to Week 28
Hide Description To compare the change from baseline to Week 28 in systolic blood pressure between exenatide once weekly (EQW) 2 mg and dapagliflozin 10 mg administered simultaneously compared to EQW 2 mg alone and dapagliflozin 10 mg alone.
Time Frame Baseline to Week 28
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all randomized patients who received at least 1 dose of study medication and had at least 1 post-baseline HbA1c assessment.
Arm/Group Title Dapagliflozin + Placebo Exenatide + Dapagliflozin Exenatide + Placebo
Hide Arm/Group Description:
Dapagliflozin 10 mg tablet administered orally once daily + matching placebo for exenatide administered as SC injection once weekly. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.
Exenatide once weekly (EQW) 2 mg administered as SC injection + dapagliflozin 10 mg tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.
Exenatide once weekly (EQW) 2 mg administered as SC injection + matching placebo for dapagliflozin tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.
Overall Number of Participants Analyzed 230 228 227
Least Squares Mean (95% Confidence Interval)
Unit of Measure: millimeters of mercury (mmHg)
-1.8
(-3.4 to -0.3)
-4.3
(-5.8 to -2.7)
-1.2
(-2.8 to 0.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Exenatide + Dapagliflozin, Exenatide + Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method Mixed Models Analysis
Comments Treatment, region, baseline HbA1c stratum (<9.0% or ≥9.0%), week, and treatment by week interaction as fixed factors; baseline value as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.0
Confidence Interval (2-Sided) 95%
-5.2 to -0.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.08
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dapagliflozin + Placebo, Exenatide + Dapagliflozin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.022
Comments [Not Specified]
Method Mixed Models Analysis
Comments Treatment, region, baseline HbA1c stratum (<9.0% or ≥9.0%), week, and treatment by week interaction as fixed factors; baseline value as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.4
Confidence Interval (2-Sided) 95%
-4.5 to -0.4
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.06
Estimation Comments [Not Specified]
Time Frame From baseline (Day 1) up to Week 104 (28-week Treatment Period + 24-week Extension Period 1 + 52-week Extension Period 2).
Adverse Event Reporting Description Treatment-emergent adverse event data is reported for the Safety Analysis set defined as all randomized patients receiving at least 1 dose of study medication. One patient who was randomized did not receive study medication (the patient was randomized in error); this patient was not counted as completing or discontinuing treatment.
 
Arm/Group Title Dapagliflozin + Placebo Exenatide + Dapagliflozin Exenatide + Placebo
Hide Arm/Group Description Dapagliflozin 10 mg tablet administered orally once daily + matching placebo for exenatide administered as SC injection once weekly. Patients continued to administer the same type and dose of metformin therapy they were using at study entry. Exenatide once weekly (EQW) 2 mg administered as SC injection + dapagliflozin 10 mg tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry. Exenatide once weekly (EQW) 2 mg administered as SC injection + matching placebo for dapagliflozin tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.
All-Cause Mortality
Dapagliflozin + Placebo Exenatide + Dapagliflozin Exenatide + Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/233 (0.86%)      3/231 (1.30%)      1/230 (0.43%)    
Hide Serious Adverse Events
Dapagliflozin + Placebo Exenatide + Dapagliflozin Exenatide + Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   18/233 (7.73%)      17/231 (7.36%)      18/230 (7.83%)    
Cardiac disorders       
Acute myocardial infarction  1  2/233 (0.86%)  2 0/231 (0.00%)  0 1/230 (0.43%)  1
Angina pectoris  1  0/233 (0.00%)  0 0/231 (0.00%)  0 1/230 (0.43%)  1
Arteriosclerosis coronary artery  1  0/233 (0.00%)  0 1/231 (0.43%)  1 0/230 (0.00%)  0
Atrial fibrillation  1  1/233 (0.43%)  1 0/231 (0.00%)  0 2/230 (0.87%)  2
Bradycardia  1  1/233 (0.43%)  1 0/231 (0.00%)  0 0/230 (0.00%)  0
Coronary artery occlusion  1  1/233 (0.43%)  1 0/231 (0.00%)  0 0/230 (0.00%)  0
Myocardial infarction  1  0/233 (0.00%)  0 0/231 (0.00%)  0 2/230 (0.87%)  2
Palpitations  1  1/233 (0.43%)  1 0/231 (0.00%)  0 0/230 (0.00%)  0
Tachycardia  1  1/233 (0.43%)  1 0/231 (0.00%)  0 0/230 (0.00%)  0
Ear and labyrinth disorders       
Tinnitus  1  1/233 (0.43%)  1 0/231 (0.00%)  0 0/230 (0.00%)  0
Endocrine disorders       
Pituitary-dependent Cushing's syndrome  1  0/233 (0.00%)  0 1/231 (0.43%)  1 0/230 (0.00%)  0
Gastrointestinal disorders       
Abdominal pain lower  1  0/233 (0.00%)  0 1/231 (0.43%)  1 0/230 (0.00%)  0
Anal haemorrhage  1  0/233 (0.00%)  0 1/231 (0.43%)  1 0/230 (0.00%)  0
Colitis  1  0/233 (0.00%)  0 1/231 (0.43%)  1 0/230 (0.00%)  0
Gastritis  1  1/233 (0.43%)  1 0/231 (0.00%)  0 0/230 (0.00%)  0
Gastrooesophageal reflux disease  1  0/233 (0.00%)  0 1/231 (0.43%)  1 0/230 (0.00%)  0
Pancreatic necrosis  1  0/233 (0.00%)  0 1/231 (0.43%)  1 0/230 (0.00%)  0
Umbilical hernia  1  0/233 (0.00%)  0 1/231 (0.43%)  1 0/230 (0.00%)  0
General disorders       
Chest pain  1  1/233 (0.43%)  1 0/231 (0.00%)  0 1/230 (0.43%)  1
Non-cardiac chest pain  1  1/233 (0.43%)  1 0/231 (0.00%)  0 0/230 (0.00%)  0
Hepatobiliary disorders       
Biliary dyskinesia  1  0/233 (0.00%)  0 1/231 (0.43%)  1 0/230 (0.00%)  0
Cholecystitis  1  0/233 (0.00%)  0 1/231 (0.43%)  1 0/230 (0.00%)  0
Cholelithiasis  1  0/233 (0.00%)  0 2/231 (0.87%)  2 1/230 (0.43%)  1
Immune system disorders       
Anaphylactic reaction  1  1/233 (0.43%)  1 0/231 (0.00%)  0 1/230 (0.43%)  1
Infections and infestations       
Cellulitis  1  0/233 (0.00%)  0 0/231 (0.00%)  0 1/230 (0.43%)  2
Diverticulitis  1  0/233 (0.00%)  0 0/231 (0.00%)  0 1/230 (0.43%)  1
Meningitis viral  1  0/233 (0.00%)  0 0/231 (0.00%)  0 1/230 (0.43%)  1
Osteomyelitis  1  1/233 (0.43%)  2 0/231 (0.00%)  0 0/230 (0.00%)  0
Pneumonia  1  0/233 (0.00%)  0 1/231 (0.43%)  1 1/230 (0.43%)  1
Injury, poisoning and procedural complications       
Rib fracture  1  0/233 (0.00%)  0 0/231 (0.00%)  0 1/230 (0.43%)  1
Splenic rupture  1  0/233 (0.00%)  0 0/231 (0.00%)  0 1/230 (0.43%)  1
Multiple injuries  1  0/233 (0.00%)  0 1/231 (0.43%)  1 0/230 (0.00%)  0
Spinal compression fracture  1  1/233 (0.43%)  1 0/231 (0.00%)  0 0/230 (0.00%)  0
Toxicity to various agents  1  0/233 (0.00%)  0 1/231 (0.43%)  1 0/230 (0.00%)  0
Investigations       
Hepatic enzyme increased  1  0/233 (0.00%)  0 0/231 (0.00%)  0 2/230 (0.87%)  2
Metabolism and nutrition disorders       
Hyperglycaemia  1  1/233 (0.43%)  1 0/231 (0.00%)  0 0/230 (0.00%)  0
Hypoglycaemia  1  1/233 (0.43%)  1 0/231 (0.00%)  0 0/230 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Exostosis  1  0/233 (0.00%)  0 1/231 (0.43%)  1 0/230 (0.00%)  0
Intervertebral disc protrusion  1  0/233 (0.00%)  0 1/231 (0.43%)  1 0/230 (0.00%)  0
Osteoarthritis  1  0/233 (0.00%)  0 1/231 (0.43%)  1 0/230 (0.00%)  0
Periarthritis  1  1/233 (0.43%)  1 0/231 (0.00%)  0 0/230 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Adenocarcinoma of colon  1  1/233 (0.43%)  1 0/231 (0.00%)  0 0/230 (0.00%)  0
Lipoma  1  1/233 (0.43%)  1 0/231 (0.00%)  0 0/230 (0.00%)  0
Pancreatic carcinoma  1  0/233 (0.00%)  0 1/231 (0.43%)  1 0/230 (0.00%)  0
Renal neoplasm  1  0/233 (0.00%)  0 0/231 (0.00%)  0 1/230 (0.43%)  1
Nervous system disorders       
Diabetic neuropathy  1  1/233 (0.43%)  1 0/231 (0.00%)  0 0/230 (0.00%)  0
Haemorrhagic stroke  1  0/233 (0.00%)  0 1/231 (0.43%)  1 0/230 (0.00%)  0
Ischaemic stroke  1  1/233 (0.43%)  1 0/231 (0.00%)  0 1/230 (0.43%)  1
Optic neuritis  1  0/233 (0.00%)  0 1/231 (0.43%)  1 0/230 (0.00%)  0
Presyncope  1  1/233 (0.43%)  1 0/231 (0.00%)  0 0/230 (0.00%)  0
Transient ischaemic attack  1  1/233 (0.43%)  1 0/231 (0.00%)  0 0/230 (0.00%)  0
Psychiatric disorders       
Anxiety  1  0/233 (0.00%)  0 1/231 (0.43%)  1 0/230 (0.00%)  0
Suicidal ideation  1  1/233 (0.43%)  1 0/231 (0.00%)  0 0/230 (0.00%)  0
Renal and urinary disorders       
Hydronephrosis  1  1/233 (0.43%)  1 0/231 (0.00%)  0 0/230 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Asthma  1  1/233 (0.43%)  2 0/231 (0.00%)  0 0/230 (0.00%)  0
Interstitial lung disease  1  0/233 (0.00%)  0 0/231 (0.00%)  0 1/230 (0.43%)  1
Skin and subcutaneous tissue disorders       
Hyperhidrosis  1  1/233 (0.43%)  1 0/231 (0.00%)  0 0/230 (0.00%)  0
Vascular disorders       
Hypertension  1  1/233 (0.43%)  1 0/231 (0.00%)  0 0/230 (0.00%)  0
Hypotension  1  0/233 (0.00%)  0 1/231 (0.43%)  1 0/230 (0.00%)  0
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Dapagliflozin + Placebo Exenatide + Dapagliflozin Exenatide + Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   73/233 (31.33%)      87/231 (37.66%)      78/230 (33.91%)    
Gastrointestinal disorders       
Diarrhoea  1  11/233 (4.72%)  14 13/231 (5.63%)  17 17/230 (7.39%)  25
Nausea  1  10/233 (4.29%)  12 13/231 (5.63%)  14 26/230 (11.30%)  29
Vomiting  1  7/233 (3.00%)  7 8/231 (3.46%)  10 12/230 (5.22%)  15
General disorders       
Injection site nodule  1  13/233 (5.58%)  22 20/231 (8.66%)  40 14/230 (6.09%)  24
Infections and infestations       
Nasopharyngitis  1  12/233 (5.15%)  15 15/231 (6.49%)  17 8/230 (3.48%)  10
Upper respiratory tract infection  1  22/233 (9.44%)  25 15/231 (6.49%)  22 17/230 (7.39%)  29
Urinary tract infection  1  16/233 (6.87%)  23 19/231 (8.23%)  31 15/230 (6.52%)  24
Nervous system disorders       
Headache  1  12/233 (5.15%)  12 16/231 (6.93%)  18 12/230 (5.22%)  12
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
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.
At least 30 days prior to submission for publication or presentation, Authors shall provide Sponsor with such material for its review. Sponsor shall have 30 days to comment. If requested by Sponsor, Authors shall withhold material for an additional 90 days to allow for the taking of measures to establish its proprietary rights. No publication or presentation shall be made unless and until any information determined at Sponsor’s sole discretion to be Confidential has been removed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Global Clinical Leader
Organization: AstraZeneca
Phone: +1 302 885 1180
EMail: ClinicalTrialTransparency@astrazeneca.com
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02229396    
Other Study ID Numbers: D5553C00003
2014-003503-29 ( EudraCT Number )
First Submitted: August 28, 2014
First Posted: September 1, 2014
Results First Submitted: August 9, 2017
Results First Posted: September 8, 2017
Last Update Posted: December 31, 2018