Trial Outcomes & Findings for A Study to Examine the Effects of Exenatide Once-Weekly Injection on Glucose Control and Safety in Asian Subjects (NCT NCT00917267)
NCT ID: NCT00917267
Last Updated: 2015-04-09
Results Overview
Change in HbA1c from baseline to Week 26.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
691 participants
Primary outcome timeframe
Baseline, Week 26
Results posted on
2015-04-09
Participant Flow
Participant milestones
| Measure |
Exenatide Once Weekly
Subcutaneous injection of 2 mg exenatide, once a week
|
Exenatide Twice Daily
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 22 weeks)
|
|---|---|---|
|
Overall Study
STARTED
|
346
|
345
|
|
Overall Study
Intent to Treat (ITT)
|
340
|
338
|
|
Overall Study
COMPLETED
|
307
|
266
|
|
Overall Study
NOT COMPLETED
|
39
|
79
|
Reasons for withdrawal
| Measure |
Exenatide Once Weekly
Subcutaneous injection of 2 mg exenatide, once a week
|
Exenatide Twice Daily
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 22 weeks)
|
|---|---|---|
|
Overall Study
Adverse Event
|
15
|
36
|
|
Overall Study
Physician Decision
|
2
|
4
|
|
Overall Study
Protocol Violation
|
9
|
18
|
|
Overall Study
Withdrawal by Subject
|
5
|
12
|
|
Overall Study
Lost to follow up
|
0
|
2
|
|
Overall Study
Entry Criteria Not Met
|
1
|
0
|
|
Overall Study
Sponsor Decision
|
5
|
5
|
|
Overall Study
Lack of Efficacy-Loss of Glucose Control
|
2
|
2
|
Baseline Characteristics
A Study to Examine the Effects of Exenatide Once-Weekly Injection on Glucose Control and Safety in Asian Subjects
Baseline characteristics by cohort
| Measure |
Exenatide Once Weekly
n=340 Participants
Subcutaneous injection of 2 mg exenatide, once a week
|
Exenatide Twice Daily
n=338 Participants
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 22 weeks)
|
Total
n=678 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
275 Participants
n=5 Participants
|
274 Participants
n=7 Participants
|
549 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
65 Participants
n=5 Participants
|
64 Participants
n=7 Participants
|
129 Participants
n=5 Participants
|
|
Age, Continuous
|
55.4 years
STANDARD_DEVIATION 10.59 • n=5 Participants
|
56.2 years
STANDARD_DEVIATION 9.99 • n=7 Participants
|
55.8 years
STANDARD_DEVIATION 10.30 • n=5 Participants
|
|
Sex: Female, Male
Female
|
157 Participants
n=5 Participants
|
154 Participants
n=7 Participants
|
311 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
183 Participants
n=5 Participants
|
184 Participants
n=7 Participants
|
367 Participants
n=5 Participants
|
|
Glycosylated hemoglobin (HbA1c)
|
8.7 percentage of total hemoglobin
STANDARD_DEVIATION 1.04 • n=5 Participants
|
8.7 percentage of total hemoglobin
STANDARD_DEVIATION 1.03 • n=7 Participants
|
8.7 percentage of total hemoglobin
STANDARD_DEVIATION 1.03 • n=5 Participants
|
|
Weight
|
69.6 kg
STANDARD_DEVIATION 12.44 • n=5 Participants
|
70.4 kg
STANDARD_DEVIATION 12.09 • n=7 Participants
|
70.0 kg
STANDARD_DEVIATION 12.26 • n=5 Participants
|
|
Background Oral Antidiabetic Agent (OAD)
Metformin (MET)
|
62 participants
n=5 Participants
|
60 participants
n=7 Participants
|
122 participants
n=5 Participants
|
|
Background Oral Antidiabetic Agent (OAD)
MET+Sulfonylurea (SU)
|
210 participants
n=5 Participants
|
216 participants
n=7 Participants
|
426 participants
n=5 Participants
|
|
Background Oral Antidiabetic Agent (OAD)
MET+SU+Thiazolidinedione (TZD)
|
6 participants
n=5 Participants
|
10 participants
n=7 Participants
|
16 participants
n=5 Participants
|
|
Background Oral Antidiabetic Agent (OAD)
MET+TZD
|
12 participants
n=5 Participants
|
9 participants
n=7 Participants
|
21 participants
n=5 Participants
|
|
Background Oral Antidiabetic Agent (OAD)
SU
|
30 participants
n=5 Participants
|
29 participants
n=7 Participants
|
59 participants
n=5 Participants
|
|
Background Oral Antidiabetic Agent (OAD)
SU+TZD
|
18 participants
n=5 Participants
|
12 participants
n=7 Participants
|
30 participants
n=5 Participants
|
|
Background Oral Antidiabetic Agent (OAD)
TZD
|
2 participants
n=5 Participants
|
2 participants
n=7 Participants
|
4 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 26Population: ITT Population: Randomized patients received at least one dose of study drug. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis.
Change in HbA1c from baseline to Week 26.
Outcome measures
| Measure |
Exenatide Once Weekly
n=307 Participants
Subcutaneous injection of 2 mg exenatide, once a week
|
Exenatide Twice Daily
n=263 Participants
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 22 weeks)
|
Exenatide Once Weekly Without SU Use at Screening
Subcutaneous injection of 2 mg exenatide, once a week and without SU use at Screening
|
Exenatide Twice Daily Without SU Use at Screening
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 22 weeks) and without SU use at Screening
|
|---|---|---|---|---|
|
Change in HbA1c From Baseline to Week 26.
|
-1.43 percentage of total hemoglobin
Standard Error 0.07
|
-1.12 percentage of total hemoglobin
Standard Error 0.07
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: ITT Population. Only patients with baseline HbA1c \> target were included in calculation. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis. Missing data at endpoint was imputed using last observation carried forward (LOCF) approach.
Percentage of patients achieving HbA1c \<=7% at Week 26 (for patients with HbA1c \>7% at baseline).
Outcome measures
| Measure |
Exenatide Once Weekly
n=332 Participants
Subcutaneous injection of 2 mg exenatide, once a week
|
Exenatide Twice Daily
n=333 Participants
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 22 weeks)
|
Exenatide Once Weekly Without SU Use at Screening
Subcutaneous injection of 2 mg exenatide, once a week and without SU use at Screening
|
Exenatide Twice Daily Without SU Use at Screening
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 22 weeks) and without SU use at Screening
|
|---|---|---|---|---|
|
Percentage of Patients Achieving HbA1c Targets <=7% at Week 26
|
46.7 percentage of patients
|
35.7 percentage of patients
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: ITT Population. Only patients with baseline HbA1c \> target were included in calculation. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis. Missing data at endpoint was imputed using LOCF approach.
Percentage of patients achieving HbA1c \<=6.5% at Week 26 (for patients with HbA1c \>6.5% at baseline).
Outcome measures
| Measure |
Exenatide Once Weekly
n=338 Participants
Subcutaneous injection of 2 mg exenatide, once a week
|
Exenatide Twice Daily
n=335 Participants
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 22 weeks)
|
Exenatide Once Weekly Without SU Use at Screening
Subcutaneous injection of 2 mg exenatide, once a week and without SU use at Screening
|
Exenatide Twice Daily Without SU Use at Screening
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 22 weeks) and without SU use at Screening
|
|---|---|---|---|---|
|
Percentage of Patients Achieving HbA1c Targets <=6.5% at Week 26
|
26.0 percentage of patients
|
15.5 percentage of patients
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: ITT Population. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis.
Change in FSG from baseline to Week 26.
Outcome measures
| Measure |
Exenatide Once Weekly
n=307 Participants
Subcutaneous injection of 2 mg exenatide, once a week
|
Exenatide Twice Daily
n=274 Participants
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 22 weeks)
|
Exenatide Once Weekly Without SU Use at Screening
Subcutaneous injection of 2 mg exenatide, once a week and without SU use at Screening
|
Exenatide Twice Daily Without SU Use at Screening
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 22 weeks) and without SU use at Screening
|
|---|---|---|---|---|
|
Change in Fasting Serum Glucose (FSG) From Baseline to Week 26
|
-40.57 mg/dL
Standard Error 2.36
|
-23.90 mg/dL
Standard Error 2.45
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: ITT Population. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis.
Change in BW from baseline to Week 26.
Outcome measures
| Measure |
Exenatide Once Weekly
n=309 Participants
Subcutaneous injection of 2 mg exenatide, once a week
|
Exenatide Twice Daily
n=265 Participants
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 22 weeks)
|
Exenatide Once Weekly Without SU Use at Screening
Subcutaneous injection of 2 mg exenatide, once a week and without SU use at Screening
|
Exenatide Twice Daily Without SU Use at Screening
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 22 weeks) and without SU use at Screening
|
|---|---|---|---|---|
|
Change in Body Weight (BW) From Baseline to Week 26
|
-1.63 kg
Standard Error 0.16
|
-2.45 kg
Standard Error 0.16
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: ITT Population. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis.
Change in TC from baseline to Week 26.
Outcome measures
| Measure |
Exenatide Once Weekly
n=309 Participants
Subcutaneous injection of 2 mg exenatide, once a week
|
Exenatide Twice Daily
n=277 Participants
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 22 weeks)
|
Exenatide Once Weekly Without SU Use at Screening
Subcutaneous injection of 2 mg exenatide, once a week and without SU use at Screening
|
Exenatide Twice Daily Without SU Use at Screening
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 22 weeks) and without SU use at Screening
|
|---|---|---|---|---|
|
Change in Total Cholesterol (TC) From Baseline to Week 26
|
-9.41 mg/dL
Standard Error 1.96
|
-8.10 mg/dL
Standard Error 2.04
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: ITT Population. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis.
Change in HDL from baseline to Week 26.
Outcome measures
| Measure |
Exenatide Once Weekly
n=309 Participants
Subcutaneous injection of 2 mg exenatide, once a week
|
Exenatide Twice Daily
n=277 Participants
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 22 weeks)
|
Exenatide Once Weekly Without SU Use at Screening
Subcutaneous injection of 2 mg exenatide, once a week and without SU use at Screening
|
Exenatide Twice Daily Without SU Use at Screening
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 22 weeks) and without SU use at Screening
|
|---|---|---|---|---|
|
Change in High-Density Lipoprotein (HDL) From Baseline to Week 26
|
-0.11 mg/dL
Standard Error 0.41
|
-0.48 mg/dL
Standard Error 0.43
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: ITT Population. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis.
Ratio of TG (measured in mg/dL) at Week 26 to baseline. Log(Post-baseline TG) - log(Baseline TG); change from baseline to Week 26 is presented as ratio of Week 26 to baseline.
Outcome measures
| Measure |
Exenatide Once Weekly
n=309 Participants
Subcutaneous injection of 2 mg exenatide, once a week
|
Exenatide Twice Daily
n=277 Participants
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 22 weeks)
|
Exenatide Once Weekly Without SU Use at Screening
Subcutaneous injection of 2 mg exenatide, once a week and without SU use at Screening
|
Exenatide Twice Daily Without SU Use at Screening
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 22 weeks) and without SU use at Screening
|
|---|---|---|---|---|
|
Ratio of Triglycerides (TG) at Week 26 to Baseline
|
0.97 ratio
Standard Error 0.02
|
0.97 ratio
Standard Error 0.03
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: ITT Population. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis. Missing data at endpoint was not imputed.
Change in systolic blood pressure and diastolic blood pressure from baseline to Week 26.
Outcome measures
| Measure |
Exenatide Once Weekly
n=337 Participants
Subcutaneous injection of 2 mg exenatide, once a week
|
Exenatide Twice Daily
n=335 Participants
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 22 weeks)
|
Exenatide Once Weekly Without SU Use at Screening
Subcutaneous injection of 2 mg exenatide, once a week and without SU use at Screening
|
Exenatide Twice Daily Without SU Use at Screening
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 22 weeks) and without SU use at Screening
|
|---|---|---|---|---|
|
Change in Blood Pressure From Baseline to Week 26
Systolic Blood Pressure
|
-5.33 mmHg
Standard Deviation 15.99
|
-5.22 mmHg
Standard Deviation 16.23
|
—
|
—
|
|
Change in Blood Pressure From Baseline to Week 26
Diastolic Blood Pressure
|
-1.47 mmHg
Standard Deviation 9.52
|
-2.24 mmHg
Standard Deviation 9.56
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to Week 26Population: ITT Population.
Major hypoglycemia: any episode with symptoms consistent with hypoglycemia that resulted in loss of consciousness or seizure with prompt recovery in response to administration of glucagon or glucose OR documented hypoglycemia (blood glucose \<3.0 mmol/L \[54 mg/dL\]) and required the assistance of another person. Minor hypoglycemia: any sign or symptom associated with hypoglycemia that is either self-treated by the patient or resolves on its own AND has a concurrent finger stick blood glucose \<3.0 mmol/L (54 mg/dL) and not classified as major hypoglycemia. Event rate per subject year was calculated for each subject: (number of events observed from a subject/exposure from a subject)\*365.25 where exposure = last post-baseline visit date - baseline visit date. Mean and Standard Error were then derived from ITT.
Outcome measures
| Measure |
Exenatide Once Weekly
n=264 Participants
Subcutaneous injection of 2 mg exenatide, once a week
|
Exenatide Twice Daily
n=267 Participants
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 22 weeks)
|
Exenatide Once Weekly Without SU Use at Screening
n=76 Participants
Subcutaneous injection of 2 mg exenatide, once a week and without SU use at Screening
|
Exenatide Twice Daily Without SU Use at Screening
n=71 Participants
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 22 weeks) and without SU use at Screening
|
|---|---|---|---|---|
|
Assessment of Event Rate of Treatment-emergent Hypoglycemic Events
Major Hypoglycemia
|
0.00 events per subject-year
Standard Error 0.000
|
0.01 events per subject-year
Standard Error 0.007
|
0.00 events per subject-year
Standard Error 0.000
|
0.00 events per subject-year
Standard Error 0.000
|
|
Assessment of Event Rate of Treatment-emergent Hypoglycemic Events
Minor Hypoglycemia
|
0.24 events per subject-year
Standard Error 0.069
|
0.59 events per subject-year
Standard Error 0.180
|
0.03 events per subject-year
Standard Error 0.027
|
0.11 events per subject-year
Standard Error 0.113
|
Adverse Events
Exenatide Once Weekly
Serious events: 13 serious events
Other events: 131 other events
Deaths: 0 deaths
Exenatide Twice Daily
Serious events: 8 serious events
Other events: 150 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Exenatide Once Weekly
n=340 participants at risk
Subcutaneous injection of 2 mg exenatide, once a week
|
Exenatide Twice Daily
n=338 participants at risk
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 22 weeks)
|
|---|---|---|
|
Nervous system disorders
Cerebral infarction
|
0.59%
2/340
|
0.00%
0/338
|
|
Cardiac disorders
Atrial tachycardia
|
0.29%
1/340
|
0.00%
0/338
|
|
Investigations
Blood calcitonin increased
|
0.29%
1/340
|
0.00%
0/338
|
|
Infections and infestations
Bronchopneumonia
|
0.29%
1/340
|
0.00%
0/338
|
|
Nervous system disorders
Cerebral artery occlusion
|
0.29%
1/340
|
0.00%
0/338
|
|
Infections and infestations
Chronic sinusitis
|
0.29%
1/340
|
0.00%
0/338
|
|
Cardiac disorders
Coronary artery disease
|
0.29%
1/340
|
0.00%
0/338
|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
0.29%
1/340
|
0.00%
0/338
|
|
Nervous system disorders
Diplegia
|
0.29%
1/340
|
0.00%
0/338
|
|
Injury, poisoning and procedural complications
Fall
|
0.29%
1/340
|
0.00%
0/338
|
|
Gastrointestinal disorders
Gastritis
|
0.29%
1/340
|
0.00%
0/338
|
|
Injury, poisoning and procedural complications
Lower limb fracture
|
0.29%
1/340
|
0.00%
0/338
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.29%
1/340
|
0.00%
0/338
|
|
Infections and infestations
Pneumonia haemophilus
|
0.29%
1/340
|
0.00%
0/338
|
|
Gastrointestinal disorders
Small intestinal haemorrhage
|
0.29%
1/340
|
0.00%
0/338
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
0.29%
1/340
|
0.00%
0/338
|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/340
|
0.30%
1/338
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.00%
0/340
|
0.30%
1/338
|
|
Vascular disorders
Aortic aneurysm
|
0.00%
0/340
|
0.30%
1/338
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/340
|
0.30%
1/338
|
|
Infections and infestations
Pneumonia
|
0.00%
0/340
|
0.30%
1/338
|
|
Infections and infestations
Pyelonephritis acute
|
0.00%
0/340
|
0.30%
1/338
|
|
Injury, poisoning and procedural complications
Tendon rupture
|
0.00%
0/340
|
0.30%
1/338
|
|
Nervous system disorders
Transient global amnesia
|
0.00%
0/340
|
0.30%
1/338
|
|
Eye disorders
Vitreous haemorrhage
|
0.00%
0/340
|
0.30%
1/338
|
Other adverse events
| Measure |
Exenatide Once Weekly
n=340 participants at risk
Subcutaneous injection of 2 mg exenatide, once a week
|
Exenatide Twice Daily
n=338 participants at risk
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 22 weeks)
|
|---|---|---|
|
General disorders
Injection site induration
|
9.7%
33/340
|
0.59%
2/338
|
|
Gastrointestinal disorders
Diarrhoea
|
9.4%
32/340
|
8.0%
27/338
|
|
Gastrointestinal disorders
Nausea
|
9.4%
32/340
|
21.6%
73/338
|
|
Gastrointestinal disorders
Vomiting
|
7.9%
27/340
|
11.5%
39/338
|
|
Metabolism and nutrition disorders
Dyslipidaemia
|
6.2%
21/340
|
6.8%
23/338
|
|
Gastrointestinal disorders
Constipation
|
5.9%
20/340
|
7.1%
24/338
|
|
General disorders
Injection site nodule
|
5.3%
18/340
|
0.00%
0/338
|
|
General disorders
Injection site pruritus
|
5.3%
18/340
|
2.7%
9/338
|
|
Metabolism and nutrition disorders
Decreased appetite
|
4.4%
15/340
|
8.3%
28/338
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60