Trial Outcomes & Findings for Efficacy and Safety of Exenatide Once Weekly Suspension in Subjects With Type 2 Diabetes (NCT NCT01652716)
NCT ID: NCT01652716
Last Updated: 2018-07-03
Results Overview
The primary objective of this study was to compare the effect on glycemic control (HbA1c) of exenatide suspension administered once weekly to that achieved by exenatide administered twice daily for 28 weeks in subjects with type 2 diabetes mellitus.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
377 participants
Primary outcome timeframe
Baseline to Week 28
Results posted on
2018-07-03
Participant Flow
Subjects were randomized across two treatment groups (exenatide once weekly and exenatide twice daily) in a ratio of 3:2 with randomization stratified by diabetes management method at screening, screening haemoglobin A1c (HbA1c) stratum and renal function.
Participant milestones
| Measure |
Experimental: Exenatide Once Weekly (QWS) Suspension
Exenatide suspension 2 mg weekly subcutaneous injection for 52 weeks (28 weeks plus an additional 24 weeks)
|
Active Comparator: Exenatide Twice Daily (BID)
Exenatide 5 mcg BID for 4 weeks followed by 10 mcg BID for 24 weeks followed by a switch to Exenatide QWS 2mg for at least 24 weeks
|
|---|---|---|
|
Overall Study
STARTED
|
229
|
148
|
|
Overall Study
Completed 28-week
|
197
|
118
|
|
Overall Study
COMPLETED
|
173
|
102
|
|
Overall Study
NOT COMPLETED
|
56
|
46
|
Reasons for withdrawal
| Measure |
Experimental: Exenatide Once Weekly (QWS) Suspension
Exenatide suspension 2 mg weekly subcutaneous injection for 52 weeks (28 weeks plus an additional 24 weeks)
|
Active Comparator: Exenatide Twice Daily (BID)
Exenatide 5 mcg BID for 4 weeks followed by 10 mcg BID for 24 weeks followed by a switch to Exenatide QWS 2mg for at least 24 weeks
|
|---|---|---|
|
Overall Study
Loss of glucose control
|
1
|
0
|
|
Overall Study
Administrative
|
0
|
2
|
|
Overall Study
Investigator decision
|
1
|
4
|
|
Overall Study
Lost to Follow-up
|
12
|
11
|
|
Overall Study
Protocol Violation
|
2
|
1
|
|
Overall Study
Adverse Event
|
7
|
10
|
|
Overall Study
Withdrawal by Subject
|
33
|
18
|
Baseline Characteristics
Efficacy and Safety of Exenatide Once Weekly Suspension in Subjects With Type 2 Diabetes
Baseline characteristics by cohort
| Measure |
Experimental: Exenatide QWS Suspension
n=229 Participants
Exenatide suspension 2 mg weekly subcutaneous injection 52 weeks (28 weeks plus an additional 24 weeks)
|
Active Comparator: Exenatide BID
n=146 Participants
Exenatide 5 mcg BID for 4 weeks followed by 10 mcg BID for 24 weeks followed by a switch to Exenatide QWS 2mg for at least 24 weeks
|
Total
n=375 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
55.6 Years
STANDARD_DEVIATION 9.98 • n=5 Participants
|
56.5 Years
STANDARD_DEVIATION 9.04 • n=7 Participants
|
56.0 Years
STANDARD_DEVIATION 9.62 • n=5 Participants
|
|
Age, Customized
<65 years
|
182 Participants
n=5 Participants
|
118 Participants
n=7 Participants
|
300 Participants
n=5 Participants
|
|
Age, Customized
>=65 years
|
47 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
75 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
81 Participants
n=5 Participants
|
54 Participants
n=7 Participants
|
135 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
148 Participants
n=5 Participants
|
92 Participants
n=7 Participants
|
240 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
54 Participants
n=5 Participants
|
34 Participants
n=7 Participants
|
88 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
174 Participants
n=5 Participants
|
112 Participants
n=7 Participants
|
286 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Unknown
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
168 Participants
n=5 Participants
|
110 Participants
n=7 Participants
|
278 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
38 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
61 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
17 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Weight
|
214.52 lbs
STANDARD_DEVIATION 49.788 • n=5 Participants
|
213.19 lbs
STANDARD_DEVIATION 40.834 • n=7 Participants
|
214.00 lbs
STANDARD_DEVIATION 46.445 • n=5 Participants
|
|
Baseline HbA1c
|
8.47 Percentage of total hemoglobin
STANDARD_DEVIATION 1.047 • n=5 Participants
|
8.51 Percentage of total hemoglobin
STANDARD_DEVIATION 1.004 • n=7 Participants
|
8.48 Percentage of total hemoglobin
STANDARD_DEVIATION 1.029 • n=5 Participants
|
|
HbA1c Stratum
<9.0%
|
159 Number of subjects
n=5 Participants
|
97 Number of subjects
n=7 Participants
|
256 Number of subjects
n=5 Participants
|
|
HbA1c Stratum
>=9.0%
|
68 Number of subjects
n=5 Participants
|
49 Number of subjects
n=7 Participants
|
117 Number of subjects
n=5 Participants
|
|
HbA1c Stratum
Not Recorded
|
2 Number of subjects
n=5 Participants
|
0 Number of subjects
n=7 Participants
|
2 Number of subjects
n=5 Participants
|
|
Fasting plasma glucose
|
180.92 mg/dL
STANDARD_DEVIATION 44.538 • n=5 Participants
|
183.77 mg/dL
STANDARD_DEVIATION 46.904 • n=7 Participants
|
182.03 mg/dL
STANDARD_DEVIATION 45.437 • n=5 Participants
|
|
Duration of diabetes
|
8.55 Years
STANDARD_DEVIATION 6.249 • n=5 Participants
|
8.47 Years
STANDARD_DEVIATION 5.961 • n=7 Participants
|
8.52 Years
STANDARD_DEVIATION 6.132 • n=5 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
The primary objective of this study was to compare the effect on glycemic control (HbA1c) of exenatide suspension administered once weekly to that achieved by exenatide administered twice daily for 28 weeks in subjects with type 2 diabetes mellitus.
Outcome measures
| Measure |
Experimental: Exenatide QWS Suspension
n=229 Participants
Exenatide suspension 2 mg weekly subcutaneous injection 52 weeks (28 weeks plus an additional 24 weeks)
|
Active Comparator: Exenatide BID
n=146 Participants
Exenatide 5 mcg BID for 4 weeks followed by 10 mcg BID for 24 weeks followed by a switch to Exenatide QWS 2mg for at least 24 weeks
|
|---|---|---|
|
Change in HbA1c (Glycosylated Hemoglobin) From Baseline to Week 28
|
-1.39 Percentage of total hemoglobin
Standard Error 0.0930
|
-1.02 Percentage of total hemoglobin
Standard Error 0.1147
|
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 \<7% at Week 28/Study Termination
Outcome measures
| Measure |
Experimental: Exenatide QWS Suspension
n=229 Participants
Exenatide suspension 2 mg weekly subcutaneous injection 52 weeks (28 weeks plus an additional 24 weeks)
|
Active Comparator: Exenatide BID
n=146 Participants
Exenatide 5 mcg BID for 4 weeks followed by 10 mcg BID for 24 weeks followed by a switch to Exenatide QWS 2mg for at least 24 weeks
|
|---|---|---|
|
Percentage of Subjects Achieving HbA1c <7% at Week 28
Baseline Yes
|
3.9 Percentage of subjects
|
1.4 Percentage of subjects
|
|
Percentage of Subjects Achieving HbA1c <7% at Week 28
Baseline No
|
95.2 Percentage of subjects
|
98.6 Percentage of subjects
|
|
Percentage of Subjects Achieving HbA1c <7% at Week 28
Week 28 Yes
|
49.3 Percentage of subjects
|
43.2 Percentage of subjects
|
|
Percentage of Subjects Achieving HbA1c <7% at Week 28
Week 28 No
|
49.8 Percentage of subjects
|
56.8 Percentage of subjects
|
|
Percentage of Subjects Achieving HbA1c <7% at Week 28
Baseline missing
|
0.9 Percentage of subjects
|
0 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.
Change in fasting plasma glucose concentrations from baseline to Week 28/Study Termination
Outcome measures
| Measure |
Experimental: Exenatide QWS Suspension
n=229 Participants
Exenatide suspension 2 mg weekly subcutaneous injection 52 weeks (28 weeks plus an additional 24 weeks)
|
Active Comparator: Exenatide BID
n=146 Participants
Exenatide 5 mcg BID for 4 weeks followed by 10 mcg BID for 24 weeks followed by a switch to Exenatide QWS 2mg for at least 24 weeks
|
|---|---|---|
|
Change in Fasting Plasma Glucose Concentrations From Baseline to Week 28
|
-32.7 mg/dL
Standard Error 3.906
|
-22.5 mg/dL
Standard Error 4.917
|
SECONDARY outcome
Timeframe: Baseline to Week 28Population: Modified Intent-to-Treat: Subjects who were randomized and received at least one dose of study drug.
Change in body weight (kg) from baseline to Week 28/Study Termination.
Outcome measures
| Measure |
Experimental: Exenatide QWS Suspension
n=229 Participants
Exenatide suspension 2 mg weekly subcutaneous injection 52 weeks (28 weeks plus an additional 24 weeks)
|
Active Comparator: Exenatide BID
n=146 Participants
Exenatide 5 mcg BID for 4 weeks followed by 10 mcg BID for 24 weeks followed by a switch to Exenatide QWS 2mg for at least 24 weeks
|
|---|---|---|
|
Change in Body Weight (kg) From Baseline to Week 28
|
-1.49 kg
Standard Error 0.2842
|
-1.89 kg
Standard Error 0.3640
|
SECONDARY outcome
Timeframe: Baseline to Week 16Population: Meal Test Evaluable Subjects: Subjects who were randomized and received at least one dose of study drug and who participated in the meal test at Visit 3 and Visit 13, had adequate and reliable data for the postprandial data evaluation, and had adequate study medication exposure.
Change in 2-hour postprandial glucose concentrations from baseline to Week 16.
Outcome measures
| Measure |
Experimental: Exenatide QWS Suspension
n=37 Participants
Exenatide suspension 2 mg weekly subcutaneous injection 52 weeks (28 weeks plus an additional 24 weeks)
|
Active Comparator: Exenatide BID
n=31 Participants
Exenatide 5 mcg BID for 4 weeks followed by 10 mcg BID for 24 weeks followed by a switch to Exenatide QWS 2mg for at least 24 weeks
|
|---|---|---|
|
Change in 2-hour Postprandial Glucose Concentrations From Baseline to Week 16
|
-87.00 mg/dL
Standard Error 12.8374
|
-113.74 mg/dL
Standard Error 14.8042
|
Adverse Events
Experimental: Exenatide QWS Suspension
Serious events: 12 serious events
Other events: 121 other events
Deaths: 0 deaths
Active Comparator: Exenatide BID
Serious events: 17 serious events
Other events: 94 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Experimental: Exenatide QWS Suspension
n=229 participants at risk
Exenatide suspension 2 mg weekly subcutaneous injection 52 weeks (28 weeks plus an additional 24 weeks)
|
Active Comparator: Exenatide BID
n=146 participants at risk
Exenatide 5 mcg BID for 4 weeks followed by 10 mcg BID for 24 weeks followed by a switch to Exenatide QWS 2mg for at least 24 weeks
|
|---|---|---|
|
Infections and infestations
Localised Infection
|
0.44%
1/229 • Number of events 1 • up to 52 week data reported
|
0.00%
0/146 • up to 52 week data reported
|
|
Infections and infestations
Salmonellosis
|
0.44%
1/229 • Number of events 1 • up to 52 week data reported
|
0.00%
0/146 • up to 52 week data reported
|
|
Infections and infestations
Cellulitis
|
0.00%
0/229 • up to 52 week data reported
|
0.68%
1/146 • Number of events 1 • up to 52 week data reported
|
|
Infections and infestations
Septic Shock
|
0.00%
0/229 • up to 52 week data reported
|
0.68%
1/146 • Number of events 1 • up to 52 week data reported
|
|
Cardiac disorders
Myocardial Infarction
|
0.44%
1/229 • Number of events 1 • up to 52 week data reported
|
0.00%
0/146 • up to 52 week data reported
|
|
Gastrointestinal disorders
Pancreatitis
|
0.87%
2/229 • Number of events 2 • up to 52 week data reported
|
0.00%
0/146 • up to 52 week data reported
|
|
Gastrointestinal disorders
Diverticular Perforation
|
0.00%
0/229 • up to 52 week data reported
|
0.68%
1/146 • Number of events 1 • up to 52 week data reported
|
|
Nervous system disorders
Syncope
|
0.44%
1/229 • Number of events 1 • up to 52 week data reported
|
0.00%
0/146 • up to 52 week data reported
|
|
Nervous system disorders
Toxic Encephalopathy
|
0.00%
0/229 • up to 52 week data reported
|
0.68%
1/146 • Number of events 1 • up to 52 week data reported
|
|
Skin and subcutaneous tissue disorders
Hidradentis
|
0.44%
1/229 • Number of events 1 • up to 52 week data reported
|
0.00%
0/146 • up to 52 week data reported
|
|
General disorders
Drug Withdrawal Syndrome
|
0.00%
0/229 • up to 52 week data reported
|
0.68%
1/146 • Number of events 1 • up to 52 week data reported
|
|
Metabolism and nutrition disorders
Lactic Acidosis
|
0.00%
0/229 • up to 52 week data reported
|
0.68%
1/146 • Number of events 1 • up to 52 week data reported
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal Cell Carcinoma
|
0.00%
0/229 • up to 52 week data reported
|
0.68%
1/146 • Number of events 1 • up to 52 week data reported
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine Leiomyoma
|
0.00%
0/229 • up to 52 week data reported
|
0.68%
1/146 • Number of events 1 • up to 52 week data reported
|
|
Renal and urinary disorders
Renal Failure Acute
|
0.00%
0/229 • up to 52 week data reported
|
0.68%
1/146 • Number of events 1 • up to 52 week data reported
|
|
Respiratory, thoracic and mediastinal disorders
Acute Pulmonary Oedema
|
0.00%
0/229 • up to 52 week data reported
|
0.68%
1/146 • Number of events 1 • up to 52 week data reported
|
|
Gastrointestinal disorders
Umbilical Hernia
|
0.44%
1/229 • Number of events 1 • up to 52 week data reported
|
0.00%
0/146 • up to 52 week data reported
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/229 • up to 52 week data reported
|
0.68%
1/146 • Number of events 1 • up to 52 week data reported
|
|
Infections and infestations
Infectious Colitis
|
0.44%
1/229 • Number of events 1 • up to 52 week data reported
|
0.00%
0/146 • up to 52 week data reported
|
|
Cardiac disorders
Acute Myocardial Infarction
|
0.00%
0/229 • up to 52 week data reported
|
0.68%
1/146 • Number of events 1 • up to 52 week data reported
|
|
Cardiac disorders
Atrial Fibrillation
|
0.00%
0/229 • up to 52 week data reported
|
0.68%
1/146 • Number of events 1 • up to 52 week data reported
|
|
Injury, poisoning and procedural complications
Lower Limb Fracture
|
0.44%
1/229 • Number of events 1 • up to 52 week data reported
|
0.00%
0/146 • up to 52 week data reported
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.44%
1/229 • Number of events 1 • up to 52 week data reported
|
0.00%
0/146 • up to 52 week data reported
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant Melanoma
|
0.44%
1/229 • Number of events 1 • up to 52 week data reported
|
0.00%
0/146 • up to 52 week data reported
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatocellular Carcinoma
|
0.00%
0/229 • up to 52 week data reported
|
0.68%
1/146 • Number of events 1 • up to 52 week data reported
|
|
Nervous system disorders
Carotid Artery Stenosis
|
0.00%
0/229 • up to 52 week data reported
|
0.68%
1/146 • Number of events 1 • up to 52 week data reported
|
|
General disorders
Chest Pain
|
0.00%
0/229 • up to 52 week data reported
|
0.68%
1/146 • Number of events 1 • up to 52 week data reported
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/229 • up to 52 week data reported
|
0.68%
1/146 • Number of events 1 • up to 52 week data reported
|
Other adverse events
| Measure |
Experimental: Exenatide QWS Suspension
n=229 participants at risk
Exenatide suspension 2 mg weekly subcutaneous injection 52 weeks (28 weeks plus an additional 24 weeks)
|
Active Comparator: Exenatide BID
n=146 participants at risk
Exenatide 5 mcg BID for 4 weeks followed by 10 mcg BID for 24 weeks followed by a switch to Exenatide QWS 2mg for at least 24 weeks
|
|---|---|---|
|
General disorders
Injection Site Nodule
|
15.7%
36/229 • Number of events 37 • up to 52 week data reported
|
4.1%
6/146 • Number of events 6 • up to 52 week data reported
|
|
Gastrointestinal disorders
Nausea
|
9.6%
22/229 • Number of events 30 • up to 52 week data reported
|
22.6%
33/146 • Number of events 38 • up to 52 week data reported
|
|
Nervous system disorders
Headache
|
6.1%
14/229 • Number of events 16 • up to 52 week data reported
|
6.2%
9/146 • Number of events 10 • up to 52 week data reported
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
6.6%
15/229 • Number of events 16 • up to 52 week data reported
|
5.5%
8/146 • Number of events 9 • up to 52 week data reported
|
|
Gastrointestinal disorders
Diarrhoea
|
6.1%
14/229 • Number of events 23 • up to 52 week data reported
|
12.3%
18/146 • Number of events 24 • up to 52 week data reported
|
|
Gastrointestinal disorders
Vomiting
|
3.9%
9/229 • Number of events 11 • up to 52 week data reported
|
7.5%
11/146 • Number of events 11 • up to 52 week data reported
|
|
Infections and infestations
Nasopharyngitis
|
4.8%
11/229 • Number of events 13 • up to 52 week data reported
|
6.2%
9/146 • Number of events 11 • up to 52 week data reported
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60