Phase III Study to Evaluate Safety and Efficacy of Added Exenatide Versus Placebo to Titrated Basal Insulin Glargine in Inadequately Controlled Patients With Type II Diabetes Mellitus

Sponsor
AstraZeneca (Industry)
Overall Status
Completed
CT.gov ID
NCT02229383
Collaborator
(none)
464
123
2
23.8
3.8
0.2

Study Details

Study Description

Brief Summary

Study D5553C00002 is a multicenter, randomized, double-blind, placebo-controlled, parallel group, Phase 3 study to compare the safety and efficacy of exenatide once weekly (EQW) added to titrated basal insulin glargine with or without metformin to placebo added to titrated basal insulin glargine with or without metformin in patients with type 2 diabetes mellitus (T2DM). Eligible patients will be randomized at Visit 5 (Day 1) to receive either EQW added to titrated basal insulin glargine, with or without metformin ≥1500 mg/day, or placebo added to titrated basal insulin glargine, with or without metformin ≥1500 mg/day, during the 28-week treatment period.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
464 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase 3 Trial to Evaluate the Safety and Efficacy of Once Weekly Exenatide Therapy Added to Titrated Basal Insulin Glargine Compared to Placebo Added to Titrated Basal Insulin Glargine in Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control on Basal Insulin Glargine With or Without Metformin
Actual Study Start Date :
Sep 6, 2014
Actual Primary Completion Date :
Aug 29, 2016
Actual Study Completion Date :
Aug 29, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: Exenatide

Exenatide 2 mg 1 time per week + titrated basal insulin glargine with or without metformin

Drug: Exenatide
2 mg weekly suspension injection

Placebo Comparator: Placebo

Placebo 2 mg 1 time per week + titrated basal insulin glargine with or without metformin

Drug: Exenatide matching placebo
Once weekly Placebo injection

Outcome Measures

Primary Outcome Measures

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

    To compare the change from baseline in HbA1c achieved with exenatide once weekly (EQW) added to titrated basal insulin glargine to placebo added to titrated basal insulin glargine, with or without metformin, after 28 weeks of double-blind treatment. SU= sulfonylurea.

Secondary Outcome Measures

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

    To compare the change from baseline in body weight achieved with EQW added to titrated basal insulin glargine to placebo added to titrated basal insulin glargine, with or without metformin, after 28 weeks of double-blind treatment.

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

    To compare the change from baseline in 2-hour postprandial glucose after a standard MTT achieved with EQW added to titrated basal insulin glargine to placebo added to titrated basal insulin glargine, with or without metformin, after 28 weeks of double-blind treatment.

  3. Percentage of Participants Achieving HbA1c <7.0% at Week 28 [Baseline to Week 28]

    To compare the percentage of participants achieving HbA1c <7.0% between EQW added to titrated basal insulin glargine to placebo added to titrated basal insulin glargine, with or without metformin, after 28 weeks of double-blind treatment.

  4. Change From Baseline to Week 28 in Daily Insulin Dose [Baseline to Week 28]

    To compare the change from baseline in daily insulin dose achieved with EQW added to titrated basal insulin glargine to placebo added to titrated basal insulin glargine, with or without metformin, after 28 weeks of double-blind treatment.

  5. Percentage of Participants Achieving HbA1c <7.0% at Week 28, No Weight Gain at Week 28, and No Major Hypoglycemia Over 28 Weeks [Baseline to Week 28]

    To compare the percentage of participants achieving HbA1c <7.0% at Week 28, no weight gain at Week 28, and no major hypoglycemia over 28 weeks between EQW added to titrated basal insulin glargine to placebo added to titrated basal insulin glargine, with or without metformin.

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

    To compare the change from baseline in seated systolic blood pressure achieved with EQW added to titrated basal insulin glargine to placebo added to titrated basal insulin glargine, with or without metformin, after 28 weeks of double-blind treatment.

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 Type 2 Diabetes Mellitus (T2DM)

  • Has HbA1c of 7.5% to 12.0%, inclusive, at Visit 1 (Screening).

  • Has fasting plasma glucose (FPG) concentration <280 mg/dL (15.6 mmol/L) at Visit 1 (Screening)

  • Treated with basal insulin glargine at a dose of ≥20 units/day once daily for at least 6 weeks prior to Screening, in combination with diet and exercise alone or in combination with:

  1. a stable dose of metformin (≥1500 mg/day) for at least 8 weeks prior to Visit 1

  2. a stable dose of metformin (≥1500 mg/day) for at least 8 weeks prior to Visit 1 (Screening) and a stable dose of sulfonylurea for at least 8 weeks prior to the Screening visit

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

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

  • Positive serological test for hepatitis B or hepatitis C

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 Muscle Shoals Alabama United States 35662
4 Research Site Tempe Arizona United States 85283
5 Research Site Chino California United States 91710
6 Research Site Chula Vista California United States 91910
7 Research Site El Cajon California United States 92020
8 Research Site Fresno California United States 93720
9 Research Site Long Beach California United States 90807
10 Research Site Los Angeles California United States 90057
11 Research Site Mission Hills California United States 91345
12 Research Site Tustin California United States 92780
13 Research Site West Hills California United States 91307
14 Research Site Boynton Beach Florida United States 33437
15 Research Site Brooksville Florida United States 34601
16 Research Site Chiefland Florida United States 32626
17 Research Site Clearwater Florida United States 33765
18 Research Site Coral Gables Florida United States 33134
19 Research Site Fort Lauderdale Florida United States 33316
20 Research Site Hialeah Florida United States 33012
21 Research Site Jacksonville Florida United States 32256
22 Research Site Jacksonville Florida United States 32277
23 Research Site Miami Florida United States 33125
24 Research Site Miami Florida United States 33126
25 Research Site Miami Florida United States 33133
26 Research Site Miami Florida United States 33142
27 Research Site Miami Florida United States 33175
28 Research Site North Miami Beach Florida United States 33162
29 Research Site Orlando Florida United States 32806
30 Research Site Tampa Florida United States 33603
31 Research Site Columbus Georgia United States 31406
32 Research Site Chicago Illinois United States 60607
33 Research Site Avon Indiana United States 46123
34 Research Site Evansville Indiana United States 47714
35 Research Site Franklin Indiana United States 46131
36 Research Site Newton Kansas United States 67114
37 Research Site Monroe Louisiana United States 71203
38 Research Site New Orleans Louisiana United States 70112
39 Research Site Hazelwood Missouri United States 63042
40 Research Site Bellevue Nebraska United States 68005
41 Research Site Omaha Nebraska United States 68114
42 Research Site Haddon Heights New Jersey United States 08035
43 Research Site Mooresville North Carolina United States 28117
44 Research Site Morehead City North Carolina United States 28557
45 Research Site Morganton North Carolina United States 28655
46 Research Site Cincinnati Ohio United States 45242
47 Research Site Cleveland Ohio United States 44122
48 Research Site Dayton Ohio United States 45417
49 Research Site Medford Oregon United States 97504
50 Research Site Philadelphia Pennsylvania United States 91307
51 Research Site Greer South Carolina United States 29651
52 Research Site Spartanburg South Carolina United States 29303
53 Research Site Dakota Dunes South Dakota United States 57049
54 Research Site Johnson City Tennessee United States 37604
55 Research Site Kingsport Tennessee United States 37660
56 Research Site Austin Texas United States 78705
57 Research Site Dallas Texas United States 75208
58 Research Site Dallas Texas United States 75230
59 Research Site Houston Texas United States 77030
60 Research Site Houston Texas United States 77070
61 Research Site Houston Texas United States 77079
62 Research Site Houston Texas United States 77090
63 Research Site Clinton Utah United States 84015
64 Research Site Ogden Utah United States 84405
65 Research Site Salt Lake City Utah United States 84102
66 Research Site Manassas Virginia United States 20110
67 Research Site Richmond Virginia United States 23294
68 Research Site Port Orchard Washington United States 98366
69 Research Site Baja Hungary 6500
70 Research Site Balatonfured Hungary 8230
71 Research Site Budapest Hungary 1033
72 Research Site Budapest Hungary 1036
73 Research Site Budapest Hungary 1083
74 Research Site Budapest Hungary 1088
75 Research Site Budapest Hungary 1134
76 Research Site Debrecen Hungary 4032
77 Research Site Eger Hungary 3300
78 Research Site Gyula Hungary 5700
79 Research Site Gödöllő Hungary 2100
80 Research Site Komárom Hungary 2921
81 Research Site Létavértes Hungary 4281
82 Research Site Pécs Hungary 7623
83 Research Site Satoraljaujhely Hungary 3980
84 Research Site Szeged Hungary 6722
85 Research Site Szekszárd Hungary 7100
86 Research Site Lublin Poland 20-363
87 Research Site Lublin Poland 20-538
88 Research Site Oświęcim Poland 32-600
89 Research Site Poznań Poland 61-655
90 Research Site Torun Poland 87-100
91 Research Site Zamość Poland 22-400
92 Research Site Zgierz Poland 95-100
93 Research Site Łódź Poland 94-048
94 Research Site Baia Mare Romania 430222
95 Research Site Bucuresti Romania 010192
96 Research Site Bucuresti Romania 010825
97 Research Site Bucuresti Romania 020475
98 Research Site Galati Romania 800578
99 Research Site Oradea Romania 410032
100 Research Site Oradea Romania 410169
101 Research Site Ploiesti Romania 100342
102 Research Site Tg Mures Romania 540142
103 Research Site Timișoara Romania 300456
104 Research Site Bardejov Slovakia 08501
105 Research Site Bratislava Slovakia 81108
106 Research Site Bratislava Slovakia 82106
107 Research Site Dolny Kubin Slovakia 026 01
108 Research Site Kosice Slovakia 04001
109 Research Site Levice Slovakia 934 01
110 Research Site Levice Slovakia 93401
111 Research Site Lucenec Slovakia 984 01
112 Research Site Nitra Slovakia 94901
113 Research Site Nitra Slovakia 94911
114 Research Site Presov Slovakia 080 01
115 Research Site Sturovo Slovakia 94301
116 Research Site Bloemfontein South Africa 9301
117 Research Site Kempton Park South Africa 1619
118 Research Site Krugersdorp South Africa 1739
119 Research Site Paarl South Africa 7646
120 Research Site Pretoria South Africa 0087
121 Research Site Pretoria South Africa 184
122 Research Site Somerset West South Africa 7130
123 Research Site Worcester South Africa 6850

Sponsors and Collaborators

  • AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT02229383
Other Study ID Numbers:
  • D5553C00002
  • 2014-003502-33
First Posted:
Sep 1, 2014
Last Update Posted:
Jan 8, 2019
Last Verified:
Dec 1, 2018

Study Results

Participant Flow

Recruitment Details This study was conducted in 107 centers globally between 06 September 2014 and 29 August 2016.
Pre-assignment Detail The study had a Screening Visit, an 8-week insulin dose optimization phase, followed by a 28-week randomized, double-blind treatment phase. A total of 464 participants were randomized and entered the double-blind Treatment Period. Of which, 3 participants from 1 center in the United States have been excluded from analyses.
Arm/Group Title Exenatide Placebo
Arm/Group Description Exenatide 2 milligram (mg) 1 time per week + titrated basal insulin glargine with or without metformin. Placebo (matching with exenatide) 1 time per week + titrated basal insulin glargine with or without metformin.
Period Title: Overall Study
STARTED 232 229
Received Treatment 231 229
Safety Analysis Set 231 229
Intent-to-treat (ITT) Analysis Set 230 228
COMPLETED 212 207
NOT COMPLETED 20 22

Baseline Characteristics

Arm/Group Title Exenatide Placebo Total
Arm/Group Description Exenatide 2 mg 1 time per week + titrated basal insulin glargine with or without metformin. Placebo (matching with exenatide) 1 time per week + titrated basal insulin glargine with or without metformin. Total of all reporting groups
Overall Participants 230 228 458
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]
57.8
(9.04)
57.5
(10.28)
57.7
(9.67)
Sex: Female, Male (Count of Participants)
Female
117
50.9%
122
53.5%
239
52.2%
Male
113
49.1%
106
46.5%
219
47.8%
Race/Ethnicity, Customized (Count of Participants)
American Indian Or Alaska Native
1
0.4%
0
0%
1
0.2%
Asian
4
1.7%
2
0.9%
6
1.3%
Black Or African American
19
8.3%
28
12.3%
47
10.3%
Native Hawaiian Or Other Pacific Islander
1
0.4%
0
0%
1
0.2%
Other
1
0.4%
4
1.8%
5
1.1%
White
204
88.7%
194
85.1%
398
86.9%

Outcome Measures

1. Primary Outcome
Title Change in HbA1c From Baseline to Week 28
Description To compare the change from baseline in HbA1c achieved with exenatide once weekly (EQW) added to titrated basal insulin glargine to placebo added to titrated basal insulin glargine, with or without metformin, after 28 weeks of double-blind treatment. SU= sulfonylurea.
Time Frame Baseline to Week 28

Outcome Measure Data

Analysis Population Description
The ITT analysis set included all randomized participants who received at least 1 dose of study medication and had at least 1 post-baseline HbA1c assessment. Only participants with data available for analysis are presented.
Arm/Group Title Exenatide Placebo
Arm/Group Description Exenatide 2 mg 1 time per week + titrated basal insulin glargine with or without metformin. Placebo (matching with exenatide) 1 time per week + titrated basal insulin glargine with or without metformin.
Measure Participants 230 228
Least Squares Mean (95% Confidence Interval) [Percentage of HbA1c]
-0.96
-0.22
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 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 (< or ≥ 9.0%), baseline SU-use, week, treatment by week interaction as fixed factors; baseline value as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.74
Confidence Interval (2-Sided) 95%
-0.94 to -0.54
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.101
Estimation Comments
2. Secondary Outcome
Title Change in Body Weight From Baseline to Week 28
Description To compare the change from baseline in body weight achieved with EQW added to titrated basal insulin glargine to placebo added to titrated basal insulin glargine, with or without metformin, after 28 weeks of double-blind treatment.
Time Frame Baseline to Week 28

Outcome Measure Data

Analysis Population Description
The ITT analysis set included all randomized participants who received at least 1 dose of study medication and had at least 1 post-baseline HbA1c assessment. Only participants with data available for analysis are presented.
Arm/Group Title Exenatide Placebo
Arm/Group Description Exenatide 2 mg 1 time per week + titrated basal insulin glargine with or without metformin. Placebo (matching with exenatide) 1 time per week + titrated basal insulin glargine with or without metformin.
Measure Participants 230 228
Least Squares Mean (95% Confidence Interval) [kilogram]
-1.04
0.48
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 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 (< or ≥ 9.0%), baseline SU-use, week, treatment by week interaction as fixed factors; baseline value as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.52
Confidence Interval (2-Sided) 95%
-2.19 to -0.85
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.341
Estimation Comments
3. Secondary Outcome
Title Change From Baseline to Week 28 in 2-hour Postprandial Glucose After a Standard Meal Tolerance Test (MTT)
Description To compare the change from baseline in 2-hour postprandial glucose after a standard MTT achieved with EQW added to titrated basal insulin glargine to placebo added to titrated basal insulin glargine, with or without metformin, after 28 weeks of double-blind treatment.
Time Frame Baseline to Week 28

Outcome Measure Data

Analysis Population Description
The ITT analysis set included all randomized participants who received at least 1 dose of study medication and had at least 1 post-baseline HbA1c assessment. Only participants with data available for analysis are presented.
Arm/Group Title Exenatide Placebo
Arm/Group Description Exenatide 2 mg 1 time per week + titrated basal insulin glargine with or without metformin. Placebo (matching with exenatide) 1 time per week + titrated basal insulin glargine with or without metformin.
Measure Participants 230 228
Least Squares Mean (95% Confidence Interval) [milligram per deciliter]
-28.73
-0.96
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 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, baseline HbA1c (< or ≥ 9.0%), baseline SU-use (yes vs. no) as fixed factors; baseline value as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -27.76
Confidence Interval (2-Sided) 95%
-39.07 to -16.45
Parameter Dispersion Type: Standard Error of the Mean
Value: 5.754
Estimation Comments
4. Secondary Outcome
Title Percentage of Participants Achieving HbA1c <7.0% at Week 28
Description To compare the percentage of participants achieving HbA1c <7.0% between EQW added to titrated basal insulin glargine to placebo added to titrated basal insulin glargine, with or without metformin, after 28 weeks of double-blind treatment.
Time Frame Baseline to Week 28

Outcome Measure Data

Analysis Population Description
The ITT analysis set included all randomized participants who received at least 1 dose of study medication and had at least 1 post-baseline HbA1c assessment.
Arm/Group Title Exenatide Placebo
Arm/Group Description Exenatide 2 mg 1 time per week + titrated basal insulin glargine with or without metformin. Placebo (matching with exenatide) 1 time per week + titrated basal insulin glargine with or without metformin.
Measure Participants 230 228
Number (95% Confidence Interval) [Percentage of participants]
32.6
14.2%
7.0
3.1%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 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%) and baseline SU-use (yes vs. no).
Method of Estimation Estimation Parameter Difference in percentages
Estimated Value 25.6
Confidence Interval (2-Sided) %
to
Parameter Dispersion Type:
Value:
Estimation Comments
5. Secondary Outcome
Title Change From Baseline to Week 28 in Daily Insulin Dose
Description To compare the change from baseline in daily insulin dose achieved with EQW added to titrated basal insulin glargine to placebo added to titrated basal insulin glargine, with or without metformin, after 28 weeks of double-blind treatment.
Time Frame Baseline to Week 28

Outcome Measure Data

Analysis Population Description
The ITT analysis set included all randomized participants who received at least 1 dose of study medication and had at least 1 post-baseline HbA1c assessment. Only participants with data available for analysis are presented.
Arm/Group Title Exenatide Placebo
Arm/Group Description Exenatide 2 mg 1 time per week + titrated basal insulin glargine with or without metformin. Placebo (matching with exenatide) 1 time per week + titrated basal insulin glargine with or without metformin.
Measure Participants 230 228
Least Squares Mean (95% Confidence Interval) [Units]
1.6
3.5
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Exenatide, Placebo
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.074
Comments
Method Mixed Models Analysis
Comments Treatment, region, baseline HbA1c (< or ≥ 9.0%), baseline SU-use, week, treatment by week interaction as fixed factors; baseline value as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.9
Confidence Interval (2-Sided) 95%
-4.1 to 0.2
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.08
Estimation Comments
6. Secondary Outcome
Title Percentage of Participants Achieving HbA1c <7.0% at Week 28, No Weight Gain at Week 28, and No Major Hypoglycemia Over 28 Weeks
Description To compare the percentage of participants achieving HbA1c <7.0% at Week 28, no weight gain at Week 28, and no major hypoglycemia over 28 weeks between EQW added to titrated basal insulin glargine to placebo added to titrated basal insulin glargine, with or without metformin.
Time Frame Baseline to Week 28

Outcome Measure Data

Analysis Population Description
The ITT analysis set included all randomized participants who received at least 1 dose of study medication and had at least 1 post-baseline HbA1c assessment.
Arm/Group Title Exenatide Placebo
Arm/Group Description Exenatide 2 mg 1 time per week + titrated basal insulin glargine with or without metformin. Placebo (matching with exenatide) 1 time per week + titrated basal insulin glargine with or without metformin.
Measure Participants 230 228
Number (95% Confidence Interval) [Percentage of participants]
22.2
9.7%
2.2
1%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 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%) and baseline SU-use (yes vs. no).
Method of Estimation Estimation Parameter Difference in percentages
Estimated Value 20.0
Confidence Interval (2-Sided) %
to
Parameter Dispersion Type:
Value:
Estimation Comments
7. Secondary Outcome
Title Change in Seated Systolic Blood Pressure From Baseline to Week 28
Description To compare the change from baseline in seated systolic blood pressure achieved with EQW added to titrated basal insulin glargine to placebo added to titrated basal insulin glargine, with or without metformin, after 28 weeks of double-blind treatment.
Time Frame Baseline to Week 28

Outcome Measure Data

Analysis Population Description
The ITT analysis set included all randomized participants who received at least 1 dose of study medication and had at least 1 post-baseline HbA1c assessment. Only participants with data available for analysis are presented.
Arm/Group Title Exenatide Placebo
Arm/Group Description Exenatide 2 mg 1 time per week + titrated basal insulin glargine with or without metformin. Placebo (matching with exenatide) 1 time per week + titrated basal insulin glargine with or without metformin.
Measure Participants 230 228
Least Squares Mean (95% Confidence Interval) [millimeter of mercury]
-2.5
-0.7
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Exenatide, Placebo
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.110
Comments
Method Mixed Models Analysis
Comments Treatment, region, baseline HbA1c (< or ≥ 9.0%), baseline SU-use, week, treatment by week interaction as fixed factors; baseline value as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.8
Confidence Interval (2-Sided) 95%
-4.0 to 0.4
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.13
Estimation Comments

Adverse Events

Time Frame From Baseline (Day 1) up to Week 28
Adverse Event Reporting Description Safety analysis set included all participants who received at least 1 dose of randomized study medication. All-Cause Mortality is reported for the overall study period, including the off-treatment period; Serious and Other adverse event data is reported for the on-treatment period.
Arm/Group Title Exenatide Placebo
Arm/Group Description Exenatide 2 mg 1 time per week + titrated basal insulin glargine with or without metformin. Placebo (matching with exenatide) 1 time per week + titrated basal insulin glargine with or without metformin.
All Cause Mortality
Exenatide Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/231 (0%) 1/229 (0.4%)
Serious Adverse Events
Exenatide Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 11/231 (4.8%) 11/229 (4.8%)
Cardiac disorders
Angina unstable 0/231 (0%) 0 1/229 (0.4%) 1
Cardiac failure congestive 0/231 (0%) 0 2/229 (0.9%) 2
Coronary artery disease 1/231 (0.4%) 1 1/229 (0.4%) 1
Coronary artery stenosis 1/231 (0.4%) 1 0/229 (0%) 0
Myocardial infarction 0/231 (0%) 0 1/229 (0.4%) 1
Gastrointestinal disorders
Abdominal mass 1/231 (0.4%) 1 0/229 (0%) 0
Abdominal pain 1/231 (0.4%) 1 0/229 (0%) 0
Large intestine polyp 1/231 (0.4%) 1 0/229 (0%) 0
General disorders
Chest pain 1/231 (0.4%) 1 0/229 (0%) 0
Infections and infestations
Appendicitis 0/231 (0%) 0 1/229 (0.4%) 1
Cellulitis 1/231 (0.4%) 1 1/229 (0.4%) 1
Diverticulitis 0/231 (0%) 0 1/229 (0.4%) 1
Osteomyelitis 1/231 (0.4%) 1 0/229 (0%) 0
Pneumonia 0/231 (0%) 0 1/229 (0.4%) 1
Injury, poisoning and procedural complications
Humerus fracture 1/231 (0.4%) 1 0/229 (0%) 0
Toxicity to various agents 1/231 (0.4%) 1 0/229 (0%) 0
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain 0/231 (0%) 0 2/229 (0.9%) 2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma 1/231 (0.4%) 1 0/229 (0%) 0
Nervous system disorders
Carpal tunnel syndrome 0/231 (0%) 0 1/229 (0.4%) 1
Headache 0/231 (0%) 0 1/229 (0.4%) 1
Neuralgia 0/231 (0%) 0 1/229 (0.4%) 1
Psychiatric disorders
Acute stress disorder 1/231 (0.4%) 1 0/229 (0%) 0
Alcohol withdrawal syndrome 1/231 (0.4%) 1 0/229 (0%) 0
Depression 1/231 (0.4%) 1 0/229 (0%) 0
Renal and urinary disorders
Acute kidney injury 1/231 (0.4%) 1 0/229 (0%) 0
Bladder neck obstruction 0/231 (0%) 0 1/229 (0.4%) 1
Skin and subcutaneous tissue disorders
Psoriasis 1/231 (0.4%) 1 0/229 (0%) 0
Other (Not Including Serious) Adverse Events
Exenatide Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 40/231 (17.3%) 36/229 (15.7%)
Gastrointestinal disorders
Nausea 12/231 (5.2%) 13 9/229 (3.9%) 10
General disorders
Injection site nodule 12/231 (5.2%) 14 1/229 (0.4%) 1
Infections and infestations
Urinary tract infection 18/231 (7.8%) 25 15/229 (6.6%) 21
Investigations
Blood creatine phosphokinase increased 5/231 (2.2%) 6 13/229 (5.7%) 15

Limitations/Caveats

Please note that the data from 4 subjects enrolled at one site were omitted due to potential scientific misconduct at that site. Study conclusions remain unchanged.

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:
NCT02229383
Other Study ID Numbers:
  • D5553C00002
  • 2014-003502-33
First Posted:
Sep 1, 2014
Last Update Posted:
Jan 8, 2019
Last Verified:
Dec 1, 2018