Trial Outcomes & Findings for 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 (NCT NCT01652729)
NCT ID: NCT01652729
Last Updated: 2015-08-20
Results Overview
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.
COMPLETED
PHASE3
365 participants
Baseline to Week 28
2015-08-20
Participant Flow
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%).
Participant milestones
| Measure |
Experimental: Exenatide
Exenatide once weekly suspension 2mg subcutaneous injection
|
Active Comparator: Sitagliptin
Sitagliptin 100mg oral tablet once daily
|
Placebo Comparator: Placebo
Placebo oral tablet once daily
|
|---|---|---|---|
|
Overall Study
STARTED
|
182
|
122
|
61
|
|
Overall Study
Modified Intent-to-Treat
|
181
|
122
|
61
|
|
Overall Study
Treated
|
181
|
122
|
61
|
|
Overall Study
Evaluable
|
143
|
91
|
43
|
|
Overall Study
Meal Test Subjects
|
60
|
41
|
20
|
|
Overall Study
Meal Test Evaluable
|
44
|
31
|
15
|
|
Overall Study
COMPLETED
|
155
|
109
|
47
|
|
Overall Study
NOT COMPLETED
|
27
|
13
|
14
|
Reasons for withdrawal
| Measure |
Experimental: Exenatide
Exenatide once weekly suspension 2mg subcutaneous injection
|
Active Comparator: Sitagliptin
Sitagliptin 100mg oral tablet once daily
|
Placebo Comparator: Placebo
Placebo oral tablet once daily
|
|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
14
|
7
|
7
|
|
Overall Study
Adverse Event
|
4
|
0
|
3
|
|
Overall Study
Physician Decision
|
1
|
0
|
1
|
|
Overall Study
Protocol Violation
|
1
|
0
|
0
|
|
Overall Study
Lost to Follow-up
|
6
|
6
|
3
|
|
Overall Study
Administrative
|
1
|
0
|
0
|
Baseline Characteristics
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
Baseline characteristics by cohort
| Measure |
Experimental: Exenatide
n=181 Participants
Exenatide once weekly suspension 2mg subcutaneous injection
|
Active Comparator: Sitagliptin
n=122 Participants
Sitagliptin 100mg oral tablet once daily
|
Placebo Comparator: Placebo
n=61 Participants
Placebo oral tablet once daily
|
Total
n=364 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
53.4 Years
STANDARD_DEVIATION 9.82 • n=5 Participants
|
54.3 Years
STANDARD_DEVIATION 9.01 • n=7 Participants
|
53.4 Years
STANDARD_DEVIATION 9.48 • n=5 Participants
|
53.7 Years
STANDARD_DEVIATION 9.49 • n=4 Participants
|
|
Age, Customized
<65 years
|
154 Participants
n=5 Participants
|
106 Participants
n=7 Participants
|
54 Participants
n=5 Participants
|
314 Participants
n=4 Participants
|
|
Age, Customized
>=65 years
|
27 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
50 Participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
92 Participants
n=5 Participants
|
56 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
172 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
89 Participants
n=5 Participants
|
66 Participants
n=7 Participants
|
37 Participants
n=5 Participants
|
192 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White
|
148 Participants
n=5 Participants
|
98 Participants
n=7 Participants
|
50 Participants
n=5 Participants
|
296 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
24 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
49 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Asian
|
9 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
111 Participants
n=5 Participants
|
77 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
220 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
70 Participants
n=5 Participants
|
45 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
144 Participants
n=4 Participants
|
|
Weight
|
89.15 kg
STANDARD_DEVIATION 21.413 • n=5 Participants
|
88.09 kg
STANDARD_DEVIATION 20.282 • n=7 Participants
|
88.95 kg
STANDARD_DEVIATION 20.136 • n=5 Participants
|
88.76 kg
STANDARD_DEVIATION 20.778 • n=4 Participants
|
|
Baseline HbA1c
|
8.42 percentage of total hemoglobin
STANDARD_DEVIATION 0.997 • n=5 Participants
|
8.50 percentage of total hemoglobin
STANDARD_DEVIATION 1.043 • n=7 Participants
|
8.50 percentage of total hemoglobin
STANDARD_DEVIATION 1.043 • n=5 Participants
|
8.46 percentage of total hemoglobin
STANDARD_DEVIATION 1.018 • n=4 Participants
|
|
HbA1c Stratum
< 9.0%
|
125 participants
n=5 Participants
|
83 participants
n=7 Participants
|
42 participants
n=5 Participants
|
250 participants
n=4 Participants
|
|
HbA1c Stratum
>= 9.0%
|
56 participants
n=5 Participants
|
39 participants
n=7 Participants
|
19 participants
n=5 Participants
|
114 participants
n=4 Participants
|
|
Fasting Plasma Glucose
|
178.0 mg/dL
STANDARD_DEVIATION 46.64 • n=5 Participants
|
176.9 mg/dL
STANDARD_DEVIATION 42.50 • n=7 Participants
|
172.8 mg/dL
STANDARD_DEVIATION 44.31 • n=5 Participants
|
176.8 mg/dL
STANDARD_DEVIATION 44.82 • n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline to Week 28Population: Modified Intent-to-Treat: Subjects who were randomized and received at least one dose of study drug.
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.
Outcome measures
| Measure |
Experimental: Exenatide
n=181 Participants
Exenatide once weekly suspension 2mg subcutaneous injection
|
Active Comparator: Sitagliptin
n=122 Participants
Sitagliptin 100mg oral tablet once daily
|
Placebo Comparator: Placebo
n=61 Participants
Placebo oral tablet once daily
|
|---|---|---|---|
|
Change in HbA1c (Glycosylated Hemoglobin) From Baseline to Week 28
|
-1.13 percentage of total hemoglobin
Standard Error 0.1093
|
-0.75 percentage of total hemoglobin
Standard Error 0.1324
|
-0.40 percentage of total hemoglobin
Standard Error 0.1945
|
SECONDARY outcome
Timeframe: Baseline to Week 28Population: Modified Intent-to-Treat: Subjects who were randomized and received at least one dose of study drug.
Percentage of subjects achieving HbA1c target values of \< 7.0% at Week 28/Study Termination.
Outcome measures
| Measure |
Experimental: Exenatide
n=181 Participants
Exenatide once weekly suspension 2mg subcutaneous injection
|
Active Comparator: Sitagliptin
n=122 Participants
Sitagliptin 100mg oral tablet once daily
|
Placebo Comparator: Placebo
n=61 Participants
Placebo oral tablet once daily
|
|---|---|---|---|
|
Percentage of Subjects Achieving HbA1c <7% at Week 28
Baseline Yes
|
3.3 percentage of subjects
|
1.6 percentage of subjects
|
3.3 percentage of subjects
|
|
Percentage of Subjects Achieving HbA1c <7% at Week 28
Baseline No
|
96.7 percentage of subjects
|
98.4 percentage of subjects
|
96.7 percentage of subjects
|
|
Percentage of Subjects Achieving HbA1c <7% at Week 28
Week 28 Yes
|
43.1 percentage of subjects
|
32.0 percentage of subjects
|
24.6 percentage of subjects
|
|
Percentage of Subjects Achieving HbA1c <7% at Week 28
Week 28 No
|
56.9 percentage of subjects
|
68.0 percentage of subjects
|
75.4 percentage of subjects
|
SECONDARY outcome
Timeframe: Baseline to Week 28Population: Modified Intent-to-Treat: Subjects who were randomized and received at least one dose of study drug.
The change in fasting plasma glucose concentrations from baseline (Day 1) to Week 28/Study Termination.
Outcome measures
| Measure |
Experimental: Exenatide
n=181 Participants
Exenatide once weekly suspension 2mg subcutaneous injection
|
Active Comparator: Sitagliptin
n=122 Participants
Sitagliptin 100mg oral tablet once daily
|
Placebo Comparator: Placebo
n=61 Participants
Placebo oral tablet once daily
|
|---|---|---|---|
|
Change in Fasting Plasma Glucose Concentrations From Baseline to Week 28
|
-21.3 mg/dL
Standard Error 3.864
|
-11.3 mg/dL
Standard Error 4.617
|
9.6 mg/dL
Standard Error 7.097
|
SECONDARY outcome
Timeframe: Baseline to Week 28Population: Modified Intent-to-Treat: Subjects who were randomized and received at least one dose of study drug.
The change in body weight (kg) from baseline (Day 1) to Week 28/Study Termination.
Outcome measures
| Measure |
Experimental: Exenatide
n=181 Participants
Exenatide once weekly suspension 2mg subcutaneous injection
|
Active Comparator: Sitagliptin
n=122 Participants
Sitagliptin 100mg oral tablet once daily
|
Placebo Comparator: Placebo
n=61 Participants
Placebo oral tablet once daily
|
|---|---|---|---|
|
Change in Body Weight (kg) From Baseline to Week 28
|
-1.12 kg
Standard Error 0.2592
|
-1.19 kg
Standard Error 0.3134
|
0.15 kg
Standard Error 0.4767
|
SECONDARY outcome
Timeframe: Baseline to Week 16Population: 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.
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.
Outcome measures
| Measure |
Experimental: Exenatide
n=44 Participants
Exenatide once weekly suspension 2mg subcutaneous injection
|
Active Comparator: Sitagliptin
n=31 Participants
Sitagliptin 100mg oral tablet once daily
|
Placebo Comparator: Placebo
n=15 Participants
Placebo oral tablet once daily
|
|---|---|---|---|
|
Change in 2-hour Postprandial Glucose Concentrations From Baseline to Week 16 (Visit 8)
|
-59.57 mg/dL
Standard Error 10.48
|
-23.61 mg/dL
Standard Error 13.04
|
-38.68 mg/dL
Standard Error 16.98
|
Adverse Events
Experimental: Exenatide
Active Comparator: Sitagliptin
Placebo Comparator: Placebo
Serious adverse events
| Measure |
Experimental: Exenatide
n=181 participants at risk
Exenatide once weekly suspension 2mg subcutaneous injection
|
Active Comparator: Sitagliptin
n=122 participants at risk
Sitagliptin 100mg oral tablet once daily
|
Placebo Comparator: Placebo
n=61 participants at risk
Placebo oral tablet once daily
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal Hernia Obstructive
|
0.55%
1/181 • Number of events 1
|
0.00%
0/122
|
0.00%
0/61
|
|
Gastrointestinal disorders
Diarrhoea
|
0.55%
1/181 • Number of events 1
|
0.00%
0/122
|
0.00%
0/61
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid Arthritis
|
0.55%
1/181 • Number of events 1
|
0.00%
0/122
|
0.00%
0/61
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast Cancer
|
0.55%
1/181 • Number of events 1
|
0.00%
0/122
|
0.00%
0/61
|
|
Nervous system disorders
Brain Stem Infarction
|
0.55%
1/181 • Number of events 1
|
0.00%
0/122
|
0.00%
0/61
|
|
Cardiac disorders
Acute Myocardial Infarction
|
0.00%
0/181
|
0.00%
0/122
|
1.6%
1/61 • Number of events 1
|
|
Cardiac disorders
Coronary Artery Disease
|
0.00%
0/181
|
0.00%
0/122
|
1.6%
1/61 • Number of events 1
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/181
|
0.00%
0/122
|
1.6%
1/61 • Number of events 1
|
Other adverse events
| Measure |
Experimental: Exenatide
n=181 participants at risk
Exenatide once weekly suspension 2mg subcutaneous injection
|
Active Comparator: Sitagliptin
n=122 participants at risk
Sitagliptin 100mg oral tablet once daily
|
Placebo Comparator: Placebo
n=61 participants at risk
Placebo oral tablet once daily
|
|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
8.8%
16/181 • Number of events 18
|
1.6%
2/122 • Number of events 2
|
0.00%
0/61
|
|
General disorders
Injection Site Nodule
|
7.7%
14/181 • Number of events 19
|
0.00%
0/122
|
0.00%
0/61
|
|
Infections and infestations
Nasopharyngitis
|
0.55%
1/181 • Number of events 1
|
0.00%
0/122
|
6.6%
4/61 • Number of events 4
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60