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Trial record 2 of 10799 for:    Placebo AND once

Comparison Study of the Glycemic Effects, Safety, and Tolerability of Exenatide Once Weekly Suspension to Sitagliptin and Placebo in Subjects With Type 2 Diabetes Mellitus (DURATION-NEO-2)

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ClinicalTrials.gov Identifier: NCT01652729
Recruitment Status : Completed
First Posted : July 30, 2012
Results First Posted : April 23, 2015
Last Update Posted : August 20, 2015
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Diabetes Type 2
Interventions Drug: Exenatide once weekly suspension
Drug: Sitagliptin
Drug: Placebo
Enrollment 365
Recruitment Details  
Pre-assignment Details Subjects were randomly assigned across 3 treatment groups (exenatide, sitagliptin, and placebo) in a ratio of 3:2:1, with randomization stratified by screening HbA1c stratum (< 9% or 9%).
Arm/Group Title Experimental: Exenatide Active Comparator: Sitagliptin Placebo Comparator: Placebo
Hide Arm/Group Description Exenatide once weekly suspension 2mg subcutaneous injection Sitagliptin 100mg oral tablet once daily Placebo oral tablet once daily
Period Title: Overall Study
Started 182 [1] 122 61
Modified Intent-to-Treat 181 [2] 122 61
Treated 181 [3] 122 61
Evaluable 143 [4] 91 43
Meal Test Subjects 60 41 20
Meal Test Evaluable 44 [5] 31 15
Completed 155 [6] 109 47
Not Completed 27 13 14
Reason Not Completed
Withdrawal by Subject             14             7             7
Adverse Event             4             0             3
Physician Decision             1             0             1
Protocol Violation             1             0             0
Lost to Follow-up             6             6             3
Administrative             1             0             0
[1]
One subject was enrolled twice at different sites. He was randomized to exenatide at both sites.
[2]
All randomized subjects who received at least one dose of study drug.
[3]
All subjects who received at least one dose of study medication even if not randomized.
[4]
Subjects who completed study procedures to Week 24 or beyond and had adequate study drug exposure
[5]
ITT subjects who ate >=75% of meal and did not miss 2-hour postprandial glucose measures at V3 and 8
[6]
The double-enrolled subject’s reasons for withdrawal were LTFU and PV. Only PV is shown below.
Arm/Group Title Experimental: Exenatide Active Comparator: Sitagliptin Placebo Comparator: Placebo Total
Hide Arm/Group Description Exenatide once weekly suspension 2mg subcutaneous injection Sitagliptin 100mg oral tablet once daily Placebo oral tablet once daily Total of all reporting groups
Overall Number of Baseline Participants 181 122 61 364
Hide Baseline Analysis Population Description
Modified Intent-to-Treat: Subjects who were randomized and received at least one dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 181 participants 122 participants 61 participants 364 participants
53.4  (9.82) 54.3  (9.01) 53.4  (9.48) 53.7  (9.49)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 181 participants 122 participants 61 participants 364 participants
<65 years 154 106 54 314
>=65 years 27 16 7 50
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 181 participants 122 participants 61 participants 364 participants
Female
92
  50.8%
56
  45.9%
24
  39.3%
172
  47.3%
Male
89
  49.2%
66
  54.1%
37
  60.7%
192
  52.7%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 181 participants 122 participants 61 participants 364 participants
White 148 98 50 296
Black or African American 24 18 7 49
Asian 9 2 3 14
American Indian or Alaska Native 0 2 1 3
Other 0 1 0 1
Native Hawaiian or Other Pacific Islander 0 1 0 1
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 181 participants 122 participants 61 participants 364 participants
Hispanic or Latino 111 77 32 220
Not Hispanic or Latino 70 45 29 144
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 181 participants 122 participants 61 participants 364 participants
89.15  (21.413) 88.09  (20.282) 88.95  (20.136) 88.76  (20.778)
Baseline HbA1c  
Mean (Standard Deviation)
Unit of measure:  Percentage of total hemoglobin
Number Analyzed 181 participants 122 participants 61 participants 364 participants
8.42  (0.997) 8.50  (1.043) 8.50  (1.043) 8.46  (1.018)
HbA1c Stratum  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 181 participants 122 participants 61 participants 364 participants
< 9.0% 125 83 42 250
>= 9.0% 56 39 19 114
Fasting Plasma Glucose  
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 181 participants 122 participants 61 participants 364 participants
178.0  (46.64) 176.9  (42.50) 172.8  (44.31) 176.8  (44.82)
1.Primary Outcome
Title Change in HbA1c (Glycosylated Hemoglobin) From Baseline to Week 28
Hide Description Absolute change in HbA1c from baseline (Day 1, Visit 3) to Week 28/Study Termination (Visit 11). Hypothesis testing on the primary endpoint followed a serial gated procedure with all tests carried out at a 2-sided significance level of 0.05 to protect the family-wise error rate. These tests were conducted sequentially, and are presented in the statistical analysis section below in the order in which they were performed; each test was the gatekeeper of later tests.
Time Frame Baseline to Week 28
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat: Subjects who were randomized and received at least one dose of study drug.
Arm/Group Title Experimental: Exenatide Active Comparator: Sitagliptin Placebo Comparator: Placebo
Hide Arm/Group Description:
Exenatide once weekly suspension 2mg subcutaneous injection
Sitagliptin 100mg oral tablet once daily
Placebo oral tablet once daily
Overall Number of Participants Analyzed 181 122 61
Least Squares Mean (Standard Error)
Unit of Measure: percentage of total hemoglobin
-1.13  (0.1093) -0.75  (0.1324) -0.40  (0.1945)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Experimental: Exenatide, Placebo Comparator: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0010
Comments [Not Specified]
Method mixed model for repeated measure
Comments MMRM includes treatment, baseline HbA1c (<9% or ≥9%), week of visit and treatment by visit interaction as fixed factors, and subject random effect.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.72
Confidence Interval (2-Sided) 95%
-1.15 to -0.30
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.2167
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Experimental: Exenatide, Active Comparator: Sitagliptin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0209
Comments [Not Specified]
Method mixed model for repeated measure
Comments MMRM includes treatment, baseline HbA1c (<9% or ≥9%), week of visit and treatment by visit interaction as fixed factors, and subject random effect.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.38
Confidence Interval (2-Sided) 95%
-0.70 to -0.06
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.1638
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Active Comparator: Sitagliptin, Placebo Comparator: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1347
Comments [Not Specified]
Method mixed model for repeated measure
Comments MMRM includes treatment, baseline HbA1c (<9% or ≥9%), week of visit and treatment by visit interaction as fixed factors, and subject random effect.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.34
Confidence Interval (2-Sided) 95%
-0.79 to 0.11
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.2278
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Subjects Achieving HbA1c <7% at Week 28
Hide Description Percentage of subjects achieving HbA1c target values of < 7.0% at Week 28/Study Termination.
Time Frame Baseline to Week 28
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat: Subjects who were randomized and received at least one dose of study drug.
Arm/Group Title Experimental: Exenatide Active Comparator: Sitagliptin Placebo Comparator: Placebo
Hide Arm/Group Description:
Exenatide once weekly suspension 2mg subcutaneous injection
Sitagliptin 100mg oral tablet once daily
Placebo oral tablet once daily
Overall Number of Participants Analyzed 181 122 61
Measure Type: Number
Unit of Measure: percentage of subjects
Baseline Yes 3.3 1.6 3.3
Baseline No 96.7 98.4 96.7
Week 28 Yes 43.1 32.0 24.6
Week 28 No 56.9 68.0 75.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Experimental: Exenatide, Active Comparator: Sitagliptin
Comments Percentage of Subjects Achieving HbA1c <7% at Week 28.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0489
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Experimental: Exenatide, Placebo Comparator: Placebo
Comments Percentage of Subjects Achieving HbA1c <7% at Week 28.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0103
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
3.Secondary Outcome
Title Change in Fasting Plasma Glucose Concentrations From Baseline to Week 28
Hide Description The change in fasting plasma glucose concentrations from baseline (Day 1) to Week 28/Study Termination.
Time Frame Baseline to Week 28
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat: Subjects who were randomized and received at least one dose of study drug.
Arm/Group Title Experimental: Exenatide Active Comparator: Sitagliptin Placebo Comparator: Placebo
Hide Arm/Group Description:
Exenatide once weekly suspension 2mg subcutaneous injection
Sitagliptin 100mg oral tablet once daily
Placebo oral tablet once daily
Overall Number of Participants Analyzed 181 122 61
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
-21.3  (3.864) -11.3  (4.617) 9.6  (7.097)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Experimental: Exenatide, Active Comparator: Sitagliptin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0924
Comments [Not Specified]
Method mixed model for repeated measure
Comments MMRM includes treatment, baseline HbA1c (<9% or ≥9%), week of visit and treatment by visit interaction as fixed factors, and subject random effect.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -10.1
Confidence Interval (2-Sided) 95%
-21.8 to 1.7
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.960
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Experimental: Exenatide, Placebo Comparator: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method mixed model for repeated measure
Comments MMRM includes treatment, baseline HbA1c (<9% or ≥9%), week of visit and treatment by visit interaction as fixed factors, and subject random effect.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -30.9
Confidence Interval (2-Sided) 95%
-46.7 to -15.1
Parameter Dispersion
Type: Standard Error of the mean
Value: 8.037
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change in Body Weight (kg) From Baseline to Week 28
Hide Description The change in body weight (kg) from baseline (Day 1) to Week 28/Study Termination.
Time Frame Baseline to Week 28
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat: Subjects who were randomized and received at least one dose of study drug.
Arm/Group Title Experimental: Exenatide Active Comparator: Sitagliptin Placebo Comparator: Placebo
Hide Arm/Group Description:
Exenatide once weekly suspension 2mg subcutaneous injection
Sitagliptin 100mg oral tablet once daily
Placebo oral tablet once daily
Overall Number of Participants Analyzed 181 122 61
Least Squares Mean (Standard Error)
Unit of Measure: kg
-1.12  (0.2592) -1.19  (0.3134) 0.15  (0.4767)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Experimental: Exenatide, Active Comparator: Sitagliptin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8625
Comments Nominal p-value
Method mixed model for repeated measure
Comments MMRM includes treatment, baseline HbA1c (<9% or ≥9%), week of visit and treatment by visit interaction as fixed factors, and subject random effect.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.07
Confidence Interval (2-Sided) 95%
-0.73 to 0.87
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.4058
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Experimental: Exenatide, Placebo Comparator: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0198
Comments Nominal p-value
Method mixed model for repeated measure
Comments MMRM includes treatment, baseline HbA1c (<9% or ≥9%), week of visit and treatment by visit interaction as fixed factors, and subject random effect.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.27
Confidence Interval (2-Sided) 95%
-2.34 to -0.20
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.5419
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change in 2-hour Postprandial Glucose Concentrations From Baseline to Week 16 (Visit 8)
Hide Description The change in 2-hour postprandial plasma glucose from baseline (Day 1) to Visit 8 (Week 16) was analyzed using a general linear model including treatment, and baseline HbA1c stratum (< 9% or ≥ 9%) as fixed factors, and the baseline 2-hour postprandial plasma glucose concentrations as a covariate.
Time Frame Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Meal Test Evaluable Population: The Meal Test Evaluable Population consists of all modified ITT subjects who participated in the meal test, consumed at least 75% of the standardized meal and had no missing 2-hour postprandial glucose measurements at both Visit 3 (Day 1) and Visit 8 (Week 16), and have adequate study drug exposure.
Arm/Group Title Experimental: Exenatide Active Comparator: Sitagliptin Placebo Comparator: Placebo
Hide Arm/Group Description:
Exenatide once weekly suspension 2mg subcutaneous injection
Sitagliptin 100mg oral tablet once daily
Placebo oral tablet once daily
Overall Number of Participants Analyzed 44 31 15
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
-59.57  (10.48) -23.61  (13.04) -38.68  (16.98)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Experimental: Exenatide, Active Comparator: Sitagliptin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0248
Comments Nominal p-value
Method general linear model
Comments Includes treatment and baseline HbA1c (< 9% or ≥ 9%) as fixed factors, and baseline 2-hour postprandial plasma glucose concentrations as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -35.96
Confidence Interval (2-Sided) 95%
-67.23 to -4.68
Parameter Dispersion
Type: Standard Error of the mean
Value: 15.71
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Experimental: Exenatide, Placebo Comparator: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2914
Comments Nominal p-value
Method general linear model
Comments Includes treatment and baseline HbA1c (< 9% or ≥ 9%) as fixed factors, and baseline 2-hour postprandial plasma glucose concentrations as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -20.89
Confidence Interval (2-Sided) 95%
-60.02 to 18.25
Parameter Dispersion
Type: Standard Error of the mean
Value: 19.66
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Experimental: Exenatide Active Comparator: Sitagliptin Placebo Comparator: Placebo
Hide Arm/Group Description Exenatide once weekly suspension 2mg subcutaneous injection Sitagliptin 100mg oral tablet once daily Placebo oral tablet once daily
All-Cause Mortality
Experimental: Exenatide Active Comparator: Sitagliptin Placebo Comparator: Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Experimental: Exenatide Active Comparator: Sitagliptin Placebo Comparator: Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/181 (2.76%)      0/122 (0.00%)      2/61 (3.28%)    
Cardiac disorders       
Acute Myocardial Infarction  0/181 (0.00%)  0 0/122 (0.00%)  0 1/61 (1.64%)  1
Coronary Artery Disease  0/181 (0.00%)  0 0/122 (0.00%)  0 1/61 (1.64%)  1
Gastrointestinal disorders       
Abdominal Hernia Obstructive  1/181 (0.55%)  1 0/122 (0.00%)  0 0/61 (0.00%)  0
Diarrhoea  1/181 (0.55%)  1 0/122 (0.00%)  0 0/61 (0.00%)  0
Injury, poisoning and procedural complications       
Fall  0/181 (0.00%)  0 0/122 (0.00%)  0 1/61 (1.64%)  1
Musculoskeletal and connective tissue disorders       
Rheumatoid Arthritis  1/181 (0.55%)  1 0/122 (0.00%)  0 0/61 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Breast Cancer  1/181 (0.55%)  1 0/122 (0.00%)  0 0/61 (0.00%)  0
Nervous system disorders       
Brain Stem Infarction  1/181 (0.55%)  1 0/122 (0.00%)  0 0/61 (0.00%)  0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Experimental: Exenatide Active Comparator: Sitagliptin Placebo Comparator: Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   31/181 (17.13%)      2/122 (1.64%)      4/61 (6.56%)    
Gastrointestinal disorders       
Nausea  16/181 (8.84%)  18 2/122 (1.64%)  2 0/61 (0.00%)  0
General disorders       
Injection Site Nodule  14/181 (7.73%)  19 0/122 (0.00%)  0 0/61 (0.00%)  0
Infections and infestations       
Nasopharyngitis  1/181 (0.55%)  1 0/122 (0.00%)  0 4/61 (6.56%)  4
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.
Results Point of Contact
Name/Title: ClinicalTrialTransparency@astrazeneca.com
Organization: AstraZeneca
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01652729     History of Changes
Other Study ID Numbers: BCB120
MB001-004 ( Other Identifier: Bristol Myers Squibb )
First Submitted: July 26, 2012
First Posted: July 30, 2012
Results First Submitted: April 3, 2015
Results First Posted: April 23, 2015
Last Update Posted: August 20, 2015