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

Sponsor
AstraZeneca (Industry)
Overall Status
Completed
CT.gov ID
NCT02229396
Collaborator
(none)
695
134
3
39.8
5.2
0.1

Study Details

Study Description

Brief Summary

Study D5553C0003 is a 28-week, randomized, double-blind, active-controlled, multicenter, Phase 3 efficacy and safety study with 24-week and 52-week extension phases of simultaneous administration of exenatide once weekly (EQW) 2 mg and dapagliflozin 10 mg once daily (QD) compared to EQW 2 mg alone and dapagliflozin 10 mg QD alone in patients with Type 2 diabetes who have inadequate glycemic control on metformin.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
695 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A 28-week, Multicenter, Randomized, Double-Blind, Active-Controlled, Phase 3 Study With a 24-week Extension Phase Followed by a 52-week Extension Phase to Evaluate the Efficacy and Safety of Simultaneous Administration of Exenatide Once Weekly 2 mg and Dapagliflozin Once Daily 10 mg Compared to Exenatide Once Weekly 2 mg Alone and Dapagliflozin Once Daily 10 mg Alone in Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin
Actual Study Start Date :
Sep 4, 2014
Actual Primary Completion Date :
Apr 26, 2016
Actual Study Completion Date :
Dec 28, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: Exenatide Once Weekly 2 mg and Dapagliflozin Once Daily 10 mg

Drug: Exantide with Dapagliflozin
2 mg weekly suspension injection and 10 mg Dapagliflozin

Experimental: Exenatide Once Weekly 2 mg Alone

Drug: Exentide
2 mg

Active Comparator: Dapagliflozin Once Daily 10 mg Alone

Drug: Dapagliflozin
10 mg once daily Dapagliflozin

Outcome Measures

Primary Outcome Measures

  1. Change in HbA1c From Baseline to Week 28 [Baseline to Week 28]

    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.

Secondary Outcome Measures

  1. Change in Body Weight From Baseline to Week 28 [Baseline to Week 28]

    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.

  2. Change in Fasting Plasma Glucose From Baseline to Week 28 [Baseline to Week 28]

    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.

  3. Change From Baseline to Week 28 in 2-hour Postprandial Glucose After a Standard Meal Tolerance Test [Baseline to Week 28]

    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.

  4. Percentage of Patients Achieving Weight Loss ≥5.0% at Week 28 [Baseline to Week 28]

    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.

  5. Change in Fasting Plasma Glucose From Baseline to Week 2 [Baseline to Week 2]

    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.

  6. Percentage of Patients Achieving HbA1c <7% at Week 28 [Baseline to Week 28]

    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.

  7. Change in Systolic Blood Pressure From Baseline to Week 28 [Baseline to Week 28]

    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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 130 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No

Inclusion criteria

  • Has a diagnosis of T2DM.

  • Has HbA1c of 8.0% to 12.0%, inclusive, at Visit 1 and Visit 2.

  • Treated with a stable dose of metformin ≥1500 mg/day for at least 2 months prior to Screening.

Exclusion criteria

  • FPG ≥280 mg/dL (15.6 mmol/L).

  • Serum calcitonin concentration ≥40 pg/mL (≥40 ng/L) at Visit 1 (Screening)

  • Clinically significant abnormal free T4 values or patients needing initiation or adjustment of thyroid treatment according to the investigator.

  • Abnormal thyroid stimulating hormone (TSH) value at Screening will be further evaluated by free T4.Patients with clinically significant abnormal free T4 values will be excluded.

  • Known active proliferative retinopathy.

  • History of, or currently have, acute or chronic pancreatitis, or have triglyceride concentrations ≥500 mg/dL (≥5.65 mmol/L) at Visit 1

  • History or presence of inflammatory bowel disease or other severe GI diseases, particularly those which may impact gastric emptying, such as gastroparesis or pyloric stenosis.

  • History of gastric bypass surgery or gastric banding surgery, or either procedure is planned during the time period of the study. Current use of gastric balloons is also excluded.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Research Site Birmingham Alabama United States 35235
2 Research Site Huntsville Alabama United States 35801
3 Research Site Tuscumbia Alabama United States 35674
4 Research Site Glendale Arizona United States 85306
5 Research Site Tempe Arizona United States 85283
6 Research Site Anaheim California United States 92801
7 Research Site Chula Vista California United States 91911
8 Research Site El Cajon California United States 92020
9 Research Site Fresno California United States 93720
10 Research Site La Mesa California United States 91942
11 Research Site Long Beach California United States 90807
12 Research Site Los Angeles California United States 90057
13 Research Site Mission Hills California United States 91345
14 Research Site Montclair California United States 91763
15 Research Site Oceanside California United States 92056
16 Research Site San Diego California United States 92103
17 Research Site San Diego California United States 92114
18 Research Site Tustin California United States 92780
19 Research Site Van Nuys California United States 91405
20 Research Site Boynton Beach Florida United States 33437
21 Research Site Clearwater Florida United States 33765
22 Research Site Coral Gables Florida United States 33134
23 Research Site Fort Lauderdale Florida United States 33316
24 Research Site Hialeah Florida United States 33012
25 Research Site Jacksonville Florida United States 32256
26 Research Site Jacksonville Florida United States 32277
27 Research Site Miami Florida United States 33126
28 Research Site Miami Florida United States 33133
29 Research Site Miami Florida United States 33135
30 Research Site Miami Florida United States 33142
31 Research Site Miami Florida United States 33165
32 Research Site Miami Florida United States 33175
33 Research Site Miami Florida United States 33186
34 Research Site North Miami Beach Florida United States 33162
35 Research Site Orlando Florida United States 32801
36 Research Site Orlando Florida United States 32806
37 Research Site Tampa Florida United States 33603
38 Research Site Williston Florida United States 32696
39 Research Site Chicago Illinois United States 60607
40 Research Site Avon Indiana United States 46123
41 Research Site Evansville Indiana United States 47714
42 Research Site Franklin Indiana United States 46131
43 Research Site Muncie Indiana United States 47304
44 Research Site Newton Kansas United States 67114
45 Research Site Monroe Louisiana United States 71201
46 Research Site Hazelwood Missouri United States 63042
47 Research Site Bellevue Nebraska United States 68005
48 Research Site Las Vegas Nevada United States 89109
49 Research Site Haddon Heights New Jersey United States 08035
50 Research Site Burlington North Carolina United States 27215
51 Research Site Greensboro North Carolina United States 27408
52 Research Site Mooresville North Carolina United States 28117
53 Research Site Morehead City North Carolina United States 28557
54 Research Site Cincinnati Ohio United States 45242
55 Research Site Vandalia Ohio United States 45377
56 Research Site Medford Oregon United States 97504
57 Research Site Philadelphia Pennsylvania United States 91307
58 Research Site Charleston South Carolina United States 29407
59 Research Site Greer South Carolina United States 29651
60 Research Site Spartanburg South Carolina United States 29303
61 Research Site Summerville South Carolina United States 29485
62 Research Site Dakota Dunes South Dakota United States 57049
63 Research Site Memphis Tennessee United States 38119
64 Research Site Dallas Texas United States 75218
65 Research Site Dallas Texas United States 75230
66 Research Site Houston Texas United States 77074
67 Research Site Houston Texas United States 77079
68 Research Site Houston Texas United States 77090
69 Research Site Pearland Texas United States 77584
70 Research Site San Antonio Texas United States 78229
71 Research Site Tomball Texas United States 77375
72 Research Site Clinton Utah United States 84015
73 Research Site Salt Lake City Utah United States 84102
74 Research Site Burke Virginia United States 22015
75 Research Site Manassas Virginia United States 20110
76 Research Site Richmond Virginia United States 23294
77 Research Site Baja Hungary 6500
78 Research Site Balatonfüred Hungary 8230
79 Research Site Budapest Hungary 1033
80 Research Site Budapest Hungary 1083
81 Research Site Budapest Hungary 1088
82 Research Site Budaörs Hungary 2040
83 Research Site Debrecen Hungary 4025
84 Research Site Eger Hungary 3300
85 Research Site Godollo Hungary 2100
86 Research Site Gyula Hungary 5700
87 Research Site Gödöllő Hungary 2100
88 Research Site Kecskemét Hungary 6000
89 Research Site Komárom Hungary 2921
90 Research Site Létavértes Hungary 4281
91 Research Site Nyíregyháza Hungary 4405
92 Research Site Pécs Hungary 7623
93 Research Site Szeged Hungary 6722
94 Research Site Szekszárd Hungary 7100
95 Research Site Lodz Poland 94-255
96 Research Site Lublin Poland 20-538
97 Research Site Oświęcim Poland 32-600
98 Research Site Parczew Poland 21-200
99 Research Site Poznań Poland 61-655
100 Research Site Torun Poland 87-100
101 Research Site Zgierz Poland 95-100
102 Research Site Łódź Poland 94-048
103 Research Site Baia Mare Romania 430222
104 Research Site Bucuresti Romania 010192
105 Research Site Bucuresti Romania 010825
106 Research Site Bucuresti Romania 020475
107 Research Site Galati Romania 800578
108 Research Site Oradea Romania 410032
109 Research Site Oradea Romania 410169
110 Research Site Oradea Romania 410469
111 Research Site Ploiesti Romania 100342
112 Research Site Timișoara Romania 300456
113 Research Site Banska Bystrica Slovakia 97517
114 Research Site Bardejov Slovakia 085 01
115 Research Site Bratislava Slovakia 81108
116 Research Site Bratislava Slovakia 82106
117 Research Site Bratislava Slovakia 85101
118 Research Site Dolny Kubin Slovakia 026 01
119 Research Site Kosice Slovakia 04001
120 Research Site Levice Slovakia 934 01
121 Research Site Levice Slovakia 93401
122 Research Site Lucenec Slovakia 984 01
123 Research Site Nitra Slovakia 94911
124 Research Site Pezinok Slovakia 90201
125 Research Site Sturovo Slovakia 943 01
126 Research Site Trebišov Slovakia 07501
127 Research Site Bloemfontein South Africa 9301
128 Research Site Cape Town South Africa 7925
129 Research Site Johannesburg South Africa 1818
130 Research Site Kempton Park South Africa 1619
131 Research Site Middelburg South Africa 1055
132 Research Site Parow South Africa 7505
133 Research Site Port Elizabeth South Africa 6014
134 Research Site Pretoria South Africa 0001

Sponsors and Collaborators

  • AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT02229396
Other Study ID Numbers:
  • D5553C00003
  • 2014-003503-29
First Posted:
Sep 1, 2014
Last Update Posted:
Dec 31, 2018
Last Verified:
Dec 1, 2018

Study Results

Participant Flow

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 Detail 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
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 155 154 136
NOT COMPLETED 78 77 95

Baseline Characteristics

Arm/Group Title Dapagliflozin + Placebo Exenatide + Dapagliflozin Exenatide + Placebo Total
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 Participants 230 228 227 685
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]
54.5
(9.16)
53.8
(9.82)
54.2
(9.62)
54.2
(9.53)
Sex: Female, Male (Count of 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 (Number) [Number]
American Indian Or Alaska Native
0
0%
0
0%
2
0.9%
2
0.3%
Asian
1
0.4%
3
1.3%
1
0.4%
5
0.7%
Black Or African American
33
14.3%
34
14.9%
27
11.9%
94
13.7%
Other
7
3%
1
0.4%
3
1.3%
11
1.6%
White
189
82.2%
190
83.3%
194
85.5%
573
83.6%

Outcome Measures

1. Primary Outcome
Title Change in HbA1c From Baseline to Week 28
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

Outcome Measure Data

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
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.
Measure Participants 230 228 227
Least Squares Mean (95% Confidence Interval) [% HbA1c]
-1.39
-1.98
-1.60
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Exenatide + Dapagliflozin, Exenatide + Placebo
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.003
Comments
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
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dapagliflozin + Placebo, Exenatide + Dapagliflozin
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
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
2. Secondary Outcome
Title Change in Body Weight From Baseline to Week 28
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

Outcome Measure Data

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
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.
Measure Participants 230 228 227
Least Squares Mean (95% Confidence Interval) [kilogram]
-2.22
-3.55
-1.56
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Exenatide + Dapagliflozin, Exenatide + Placebo
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
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
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dapagliflozin + Placebo, Exenatide + Dapagliflozin
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
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
3. Secondary Outcome
Title Change in Fasting Plasma Glucose From Baseline to Week 28
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

Outcome Measure Data

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
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.
Measure Participants 230 228 227
Least Squares Mean (95% Confidence Interval) [milligrams/deciliter (mg/dL)]
-49.19
-65.83
-45.75
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Exenatide + Dapagliflozin, Exenatide + Placebo
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
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
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dapagliflozin + Placebo, Exenatide + Dapagliflozin
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
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
4. Secondary Outcome
Title Change From Baseline to Week 28 in 2-hour Postprandial Glucose After a Standard Meal Tolerance Test
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

Outcome Measure Data

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
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.
Measure Participants 230 228 227
Least Squares Mean (95% Confidence Interval) [mg/dL]
-61.05
-87.83
-60.09
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Exenatide + Dapagliflozin, Exenatide + Placebo
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
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
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dapagliflozin + Placebo, Exenatide + Dapagliflozin
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
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
5. Secondary Outcome
Title Percentage of Patients Achieving Weight Loss ≥5.0% at Week 28
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

Outcome Measure Data

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
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.
Measure Participants 230 228 227
Number (95% Confidence Interval) [% of patients]
20.0
33.3
13.7
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Exenatide + Dapagliflozin, Exenatide + Placebo
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
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
Confidence Interval () %
to
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dapagliflozin + Placebo, Exenatide + Dapagliflozin
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.001
Comments
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
Confidence Interval () %
to
Parameter Dispersion Type:
Value:
Estimation Comments
6. Secondary Outcome
Title Change in Fasting Plasma Glucose From Baseline to Week 2
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

Outcome Measure Data

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
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.
Measure Participants 230 228 227
Least Squares Mean (95% Confidence Interval) [mg/dL]
-26.31
-41.34
-21.08
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Exenatide + Dapagliflozin, Exenatide + Placebo
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
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
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dapagliflozin + Placebo, Exenatide + Dapagliflozin
Comments
Type of Statistical Test Superiority or Other
Comments
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
7. Secondary Outcome
Title Percentage of Patients Achieving HbA1c <7% at Week 28
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

Outcome Measure Data

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
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.
Measure Participants 230 228 227
Number (95% Confidence Interval) [% of patients]
19.1
44.7
26.9
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Exenatide + Dapagliflozin, Exenatide + Placebo
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
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
Confidence Interval () %
to
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dapagliflozin + Placebo, Exenatide + Dapagliflozin
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
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
Confidence Interval () %
to
Parameter Dispersion Type:
Value:
Estimation Comments
8. Secondary Outcome
Title Change in Systolic Blood Pressure From Baseline to Week 28
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

Outcome Measure Data

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
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.
Measure Participants 230 228 227
Least Squares Mean (95% Confidence Interval) [millimeters of mercury (mmHg)]
-1.8
-4.3
-1.2
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Exenatide + Dapagliflozin, Exenatide + Placebo
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.005
Comments
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
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dapagliflozin + Placebo, Exenatide + Dapagliflozin
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.022
Comments
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

Adverse Events

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
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 (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 2/233 (0.9%) 3/231 (1.3%) 1/230 (0.4%)
Serious Adverse Events
Dapagliflozin + Placebo Exenatide + Dapagliflozin Exenatide + Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 18/233 (7.7%) 17/231 (7.4%) 18/230 (7.8%)
Cardiac disorders
Acute myocardial infarction 2/233 (0.9%) 2 0/231 (0%) 0 1/230 (0.4%) 1
Angina pectoris 0/233 (0%) 0 0/231 (0%) 0 1/230 (0.4%) 1
Arteriosclerosis coronary artery 0/233 (0%) 0 1/231 (0.4%) 1 0/230 (0%) 0
Atrial fibrillation 1/233 (0.4%) 1 0/231 (0%) 0 2/230 (0.9%) 2
Bradycardia 1/233 (0.4%) 1 0/231 (0%) 0 0/230 (0%) 0
Coronary artery occlusion 1/233 (0.4%) 1 0/231 (0%) 0 0/230 (0%) 0
Myocardial infarction 0/233 (0%) 0 0/231 (0%) 0 2/230 (0.9%) 2
Palpitations 1/233 (0.4%) 1 0/231 (0%) 0 0/230 (0%) 0
Tachycardia 1/233 (0.4%) 1 0/231 (0%) 0 0/230 (0%) 0
Ear and labyrinth disorders
Tinnitus 1/233 (0.4%) 1 0/231 (0%) 0 0/230 (0%) 0
Endocrine disorders
Pituitary-dependent Cushing's syndrome 0/233 (0%) 0 1/231 (0.4%) 1 0/230 (0%) 0
Gastrointestinal disorders
Abdominal pain lower 0/233 (0%) 0 1/231 (0.4%) 1 0/230 (0%) 0
Anal haemorrhage 0/233 (0%) 0 1/231 (0.4%) 1 0/230 (0%) 0
Colitis 0/233 (0%) 0 1/231 (0.4%) 1 0/230 (0%) 0
Gastritis 1/233 (0.4%) 1 0/231 (0%) 0 0/230 (0%) 0
Gastrooesophageal reflux disease 0/233 (0%) 0 1/231 (0.4%) 1 0/230 (0%) 0
Pancreatic necrosis 0/233 (0%) 0 1/231 (0.4%) 1 0/230 (0%) 0
Umbilical hernia 0/233 (0%) 0 1/231 (0.4%) 1 0/230 (0%) 0
General disorders
Chest pain 1/233 (0.4%) 1 0/231 (0%) 0 1/230 (0.4%) 1
Non-cardiac chest pain 1/233 (0.4%) 1 0/231 (0%) 0 0/230 (0%) 0
Hepatobiliary disorders
Biliary dyskinesia 0/233 (0%) 0 1/231 (0.4%) 1 0/230 (0%) 0
Cholecystitis 0/233 (0%) 0 1/231 (0.4%) 1 0/230 (0%) 0
Cholelithiasis 0/233 (0%) 0 2/231 (0.9%) 2 1/230 (0.4%) 1
Immune system disorders
Anaphylactic reaction 1/233 (0.4%) 1 0/231 (0%) 0 1/230 (0.4%) 1
Infections and infestations
Cellulitis 0/233 (0%) 0 0/231 (0%) 0 1/230 (0.4%) 2
Diverticulitis 0/233 (0%) 0 0/231 (0%) 0 1/230 (0.4%) 1
Meningitis viral 0/233 (0%) 0 0/231 (0%) 0 1/230 (0.4%) 1
Osteomyelitis 1/233 (0.4%) 2 0/231 (0%) 0 0/230 (0%) 0
Pneumonia 0/233 (0%) 0 1/231 (0.4%) 1 1/230 (0.4%) 1
Injury, poisoning and procedural complications
Rib fracture 0/233 (0%) 0 0/231 (0%) 0 1/230 (0.4%) 1
Splenic rupture 0/233 (0%) 0 0/231 (0%) 0 1/230 (0.4%) 1
Multiple injuries 0/233 (0%) 0 1/231 (0.4%) 1 0/230 (0%) 0
Spinal compression fracture 1/233 (0.4%) 1 0/231 (0%) 0 0/230 (0%) 0
Toxicity to various agents 0/233 (0%) 0 1/231 (0.4%) 1 0/230 (0%) 0
Investigations
Hepatic enzyme increased 0/233 (0%) 0 0/231 (0%) 0 2/230 (0.9%) 2
Metabolism and nutrition disorders
Hyperglycaemia 1/233 (0.4%) 1 0/231 (0%) 0 0/230 (0%) 0
Hypoglycaemia 1/233 (0.4%) 1 0/231 (0%) 0 0/230 (0%) 0
Musculoskeletal and connective tissue disorders
Exostosis 0/233 (0%) 0 1/231 (0.4%) 1 0/230 (0%) 0
Intervertebral disc protrusion 0/233 (0%) 0 1/231 (0.4%) 1 0/230 (0%) 0
Osteoarthritis 0/233 (0%) 0 1/231 (0.4%) 1 0/230 (0%) 0
Periarthritis 1/233 (0.4%) 1 0/231 (0%) 0 0/230 (0%) 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon 1/233 (0.4%) 1 0/231 (0%) 0 0/230 (0%) 0
Lipoma 1/233 (0.4%) 1 0/231 (0%) 0 0/230 (0%) 0
Pancreatic carcinoma 0/233 (0%) 0 1/231 (0.4%) 1 0/230 (0%) 0
Renal neoplasm 0/233 (0%) 0 0/231 (0%) 0 1/230 (0.4%) 1
Nervous system disorders
Diabetic neuropathy 1/233 (0.4%) 1 0/231 (0%) 0 0/230 (0%) 0
Haemorrhagic stroke 0/233 (0%) 0 1/231 (0.4%) 1 0/230 (0%) 0
Ischaemic stroke 1/233 (0.4%) 1 0/231 (0%) 0 1/230 (0.4%) 1
Optic neuritis 0/233 (0%) 0 1/231 (0.4%) 1 0/230 (0%) 0
Presyncope 1/233 (0.4%) 1 0/231 (0%) 0 0/230 (0%) 0
Transient ischaemic attack 1/233 (0.4%) 1 0/231 (0%) 0 0/230 (0%) 0
Psychiatric disorders
Anxiety 0/233 (0%) 0 1/231 (0.4%) 1 0/230 (0%) 0
Suicidal ideation 1/233 (0.4%) 1 0/231 (0%) 0 0/230 (0%) 0
Renal and urinary disorders
Hydronephrosis 1/233 (0.4%) 1 0/231 (0%) 0 0/230 (0%) 0
Respiratory, thoracic and mediastinal disorders
Asthma 1/233 (0.4%) 2 0/231 (0%) 0 0/230 (0%) 0
Interstitial lung disease 0/233 (0%) 0 0/231 (0%) 0 1/230 (0.4%) 1
Skin and subcutaneous tissue disorders
Hyperhidrosis 1/233 (0.4%) 1 0/231 (0%) 0 0/230 (0%) 0
Vascular disorders
Hypertension 1/233 (0.4%) 1 0/231 (0%) 0 0/230 (0%) 0
Hypotension 0/233 (0%) 0 1/231 (0.4%) 1 0/230 (0%) 0
Other (Not Including Serious) Adverse Events
Dapagliflozin + Placebo Exenatide + Dapagliflozin Exenatide + Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 73/233 (31.3%) 87/231 (37.7%) 78/230 (33.9%)
Gastrointestinal disorders
Diarrhoea 11/233 (4.7%) 14 13/231 (5.6%) 17 17/230 (7.4%) 25
Nausea 10/233 (4.3%) 12 13/231 (5.6%) 14 26/230 (11.3%) 29
Vomiting 7/233 (3%) 7 8/231 (3.5%) 10 12/230 (5.2%) 15
General disorders
Injection site nodule 13/233 (5.6%) 22 20/231 (8.7%) 40 14/230 (6.1%) 24
Infections and infestations
Nasopharyngitis 12/233 (5.2%) 15 15/231 (6.5%) 17 8/230 (3.5%) 10
Upper respiratory tract infection 22/233 (9.4%) 25 15/231 (6.5%) 22 17/230 (7.4%) 29
Urinary tract infection 16/233 (6.9%) 23 19/231 (8.2%) 31 15/230 (6.5%) 24
Nervous system disorders
Headache 12/233 (5.2%) 12 16/231 (6.9%) 18 12/230 (5.2%) 12

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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

Name/Title Global Clinical Leader
Organization AstraZeneca
Phone +1 302 885 1180
Email ClinicalTrialTransparency@astrazeneca.com
Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT02229396
Other Study ID Numbers:
  • D5553C00003
  • 2014-003503-29
First Posted:
Sep 1, 2014
Last Update Posted:
Dec 31, 2018
Last Verified:
Dec 1, 2018