Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 24 of 10795 for:    Placebo AND once

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

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: NCT02229383
Recruitment Status : Completed
First Posted : September 1, 2014
Results First Posted : September 18, 2017
Last Update Posted : January 8, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Diabetes Mellitus
Interventions Drug: Exenatide
Drug: Exenatide matching placebo
Enrollment 464
Recruitment Details This study was conducted in 107 centers globally between 06 September 2014 and 29 August 2016.
Pre-assignment Details 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
Hide 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
Reason Not Completed
Adverse Event             7             4
Death             0             1
Lost to Follow-up             5             3
Withdrawal by Subject             4             6
Did not receive treatment             1             0
Other             3             8
Arm/Group Title Exenatide Placebo Total
Hide 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 Number of Baseline Participants 230 228 458
Hide Baseline Analysis Population Description
The overall number of baseline participants is comprised of the ITT analysis set: All randomized participants 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 458 participants
57.8  (9.04) 57.5  (10.28) 57.7  (9.67)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 230 participants 228 participants 458 participants
Female
117
  50.9%
122
  53.5%
239
  52.2%
Male
113
  49.1%
106
  46.5%
219
  47.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 230 participants 228 participants 458 participants
American Indian Or Alaska Native
1
   0.4%
0
   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
   0.0%
1
   0.2%
Other
1
   0.4%
4
   1.8%
5
   1.1%
White
204
  88.7%
194
  85.1%
398
  86.9%
1.Primary Outcome
Title Change in HbA1c From Baseline to Week 28
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 230 228
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Percentage of HbA1c
-0.96
(-1.12 to -0.81)
-0.22
(-0.38 to -0.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 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 (< 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 [Not Specified]
2.Secondary Outcome
Title Change in Body Weight From Baseline to Week 28
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 230 228
Least Squares Mean (95% Confidence Interval)
Unit of Measure: kilogram
-1.04
(-1.54 to -0.53)
0.48
(-0.02 to 0.98)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 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 (< 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 [Not Specified]
3.Secondary Outcome
Title Change From Baseline to Week 28 in 2-hour Postprandial Glucose After a Standard Meal Tolerance Test (MTT)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 230 228
Least Squares Mean (95% Confidence Interval)
Unit of Measure: milligram per deciliter
-28.73
(-40.0 to -17.45)
-0.96
(-12.41 to 10.48)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 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, 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 [Not Specified]
4.Secondary Outcome
Title Percentage of Participants Achieving HbA1c <7.0% at Week 28
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 230 228
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
32.6
(26.6 to 38.7)
7.0
(3.7 to 10.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 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%) and baseline SU-use (yes vs. no).
Method of Estimation Estimation Parameter Difference in percentages
Estimated Value 25.6
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline to Week 28 in Daily Insulin Dose
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 230 228
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Units
1.6
(0.1 to 3.1)
3.5
(2.0 to 5.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Exenatide, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.074
Comments [Not Specified]
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 [Not Specified]
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 230 228
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
22.2
(16.8 to 27.5)
2.2
(0.3 to 4.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 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%) and baseline SU-use (yes vs. no).
Method of Estimation Estimation Parameter Difference in percentages
Estimated Value 20.0
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change in Seated Systolic Blood Pressure From Baseline to Week 28
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 230 228
Least Squares Mean (95% Confidence Interval)
Unit of Measure: millimeter of mercury
-2.5
(-4.4 to -0.7)
-0.7
(-2.6 to 1.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Exenatide, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.110
Comments [Not Specified]
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 [Not Specified]
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
Hide 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 (%) Affected / at Risk (%)
Total   0/231 (0.00%)      1/229 (0.44%)    
Show Serious Adverse Events Hide Serious Adverse Events
Exenatide Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   11/231 (4.76%)      11/229 (4.80%)    
Cardiac disorders     
Angina unstable  1  0/231 (0.00%)  0 1/229 (0.44%)  1
Cardiac failure congestive  1  0/231 (0.00%)  0 2/229 (0.87%)  2
Coronary artery disease  1  1/231 (0.43%)  1 1/229 (0.44%)  1
Coronary artery stenosis  1  1/231 (0.43%)  1 0/229 (0.00%)  0
Myocardial infarction  1  0/231 (0.00%)  0 1/229 (0.44%)  1
Gastrointestinal disorders     
Abdominal mass  1  1/231 (0.43%)  1 0/229 (0.00%)  0
Abdominal pain  1  1/231 (0.43%)  1 0/229 (0.00%)  0
Large intestine polyp  1  1/231 (0.43%)  1 0/229 (0.00%)  0
General disorders     
Chest pain  1  1/231 (0.43%)  1 0/229 (0.00%)  0
Infections and infestations     
Appendicitis  1  0/231 (0.00%)  0 1/229 (0.44%)  1
Cellulitis  1  1/231 (0.43%)  1 1/229 (0.44%)  1
Diverticulitis  1  0/231 (0.00%)  0 1/229 (0.44%)  1
Osteomyelitis  1  1/231 (0.43%)  1 0/229 (0.00%)  0
Pneumonia  1  0/231 (0.00%)  0 1/229 (0.44%)  1
Injury, poisoning and procedural complications     
Humerus fracture  1  1/231 (0.43%)  1 0/229 (0.00%)  0
Toxicity to various agents  1  1/231 (0.43%)  1 0/229 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Musculoskeletal chest pain  1  0/231 (0.00%)  0 2/229 (0.87%)  2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Squamous cell carcinoma  1  1/231 (0.43%)  1 0/229 (0.00%)  0
Nervous system disorders     
Carpal tunnel syndrome  1  0/231 (0.00%)  0 1/229 (0.44%)  1
Headache  1  0/231 (0.00%)  0 1/229 (0.44%)  1
Neuralgia  1  0/231 (0.00%)  0 1/229 (0.44%)  1
Psychiatric disorders     
Acute stress disorder  1  1/231 (0.43%)  1 0/229 (0.00%)  0
Alcohol withdrawal syndrome  1  1/231 (0.43%)  1 0/229 (0.00%)  0
Depression  1  1/231 (0.43%)  1 0/229 (0.00%)  0
Renal and urinary disorders     
Acute kidney injury  1  1/231 (0.43%)  1 0/229 (0.00%)  0
Bladder neck obstruction  1  0/231 (0.00%)  0 1/229 (0.44%)  1
Skin and subcutaneous tissue disorders     
Psoriasis  1  1/231 (0.43%)  1 0/229 (0.00%)  0
1
Term from vocabulary, MedDRA 19.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Exenatide Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   40/231 (17.32%)      36/229 (15.72%)    
Gastrointestinal disorders     
Nausea  1  12/231 (5.19%)  13 9/229 (3.93%)  10
General disorders     
Injection site nodule  1  12/231 (5.19%)  14 1/229 (0.44%)  1
Infections and infestations     
Urinary tract infection  1  18/231 (7.79%)  25 15/229 (6.55%)  21
Investigations     
Blood creatine phosphokinase increased  1  5/231 (2.16%)  6 13/229 (5.68%)  15
1
Term from vocabulary, MedDRA 19.0
Indicates events were collected by systematic assessment
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.
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
Name/Title: Global Clinical Leader
Organization: AstraZeneca
Phone: +1 302 885 1180
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02229383     History of Changes
Other Study ID Numbers: D5553C00002
2014-003502-33 ( EudraCT Number )
First Submitted: August 28, 2014
First Posted: September 1, 2014
Results First Submitted: August 18, 2017
Results First Posted: September 18, 2017
Last Update Posted: January 8, 2019