Trial Outcomes & Findings for A Study to Evaluate the Glycemic Effects, Safety, and Tolerability of Exenatide Once Weekly in Subjects With Type 2 Diabetes Mellitus (DURATION-5) (NCT NCT00877890)

NCT ID: NCT00877890

Last Updated: 2015-04-07

Results Overview

Change in HbA1c from baseline (Day 1) to Week 24 \[Week 24 - Baseline\].

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

254 participants

Primary outcome timeframe

Day 1, Week 24

Results posted on

2015-04-07

Participant Flow

Participant milestones

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 20 weeks)
Overall Study
STARTED
129
125
Overall Study
Intent to Treat (ITT)
129
123
Overall Study
COMPLETED
109
95
Overall Study
NOT COMPLETED
20
30

Reasons for withdrawal

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 20 weeks)
Overall Study
Adverse Event
6
6
Overall Study
Lost to Follow-up
5
5
Overall Study
Protocol Violation
0
1
Overall Study
Withdrawal of Consent
6
12
Overall Study
Investigator Decision
0
2
Overall Study
Loss of Glucose Control
3
4

Baseline Characteristics

A Study to Evaluate the Glycemic Effects, Safety, and Tolerability of Exenatide Once Weekly in Subjects With Type 2 Diabetes Mellitus (DURATION-5)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Exenatide Once Weekly
n=129 Participants
Subcutaneous injection of 2 mg exenatide, once a week
Exenatide Twice Daily
n=123 Participants
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 20 weeks)
Total
n=252 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=39 Participants
0 Participants
n=41 Participants
0 Participants
n=35 Participants
Age, Categorical
Between 18 and 65 years
103 Participants
n=39 Participants
102 Participants
n=41 Participants
205 Participants
n=35 Participants
Age, Categorical
>=65 years
26 Participants
n=39 Participants
21 Participants
n=41 Participants
47 Participants
n=35 Participants
Age, Continuous
56.1 years
STANDARD_DEVIATION 11.14 • n=39 Participants
55.2 years
STANDARD_DEVIATION 10.27 • n=41 Participants
55.7 years
STANDARD_DEVIATION 10.71 • n=35 Participants
Sex: Female, Male
Female
52 Participants
n=39 Participants
55 Participants
n=41 Participants
107 Participants
n=35 Participants
Sex: Female, Male
Male
77 Participants
n=39 Participants
68 Participants
n=41 Participants
145 Participants
n=35 Participants
Glycosylated hemoglobin (HbA1c)
8.5 percentage of total hemoglobin
STANDARD_DEVIATION 1.10 • n=39 Participants
8.4 percentage of total hemoglobin
STANDARD_DEVIATION 1.23 • n=41 Participants
8.4 percentage of total hemoglobin
STANDARD_DEVIATION 1.16 • n=35 Participants
Weight
97.0 kg
STANDARD_DEVIATION 20.66 • n=39 Participants
94.3 kg
STANDARD_DEVIATION 18.94 • n=41 Participants
95.7 kg
STANDARD_DEVIATION 19.85 • n=35 Participants
Background Oral Antidiabetic Agent
Diet and Exercise
21 participants
n=39 Participants
26 participants
n=41 Participants
47 participants
n=35 Participants
Background Oral Antidiabetic Agent
Metformin (MET)
51 participants
n=39 Participants
52 participants
n=41 Participants
103 participants
n=35 Participants
Background Oral Antidiabetic Agent
Sulfonylurea (SU)
1 participants
n=39 Participants
8 participants
n=41 Participants
9 participants
n=35 Participants
Background Oral Antidiabetic Agent
Thiazolidinediones (TZD)
4 participants
n=39 Participants
2 participants
n=41 Participants
6 participants
n=35 Participants
Background Oral Antidiabetic Agent
MET+SU
34 participants
n=39 Participants
25 participants
n=41 Participants
59 participants
n=35 Participants
Background Oral Antidiabetic Agent
MET+TZD
13 participants
n=39 Participants
9 participants
n=41 Participants
22 participants
n=35 Participants
Background Oral Antidiabetic Agent
SU+MET+TZD
5 participants
n=39 Participants
1 participants
n=41 Participants
6 participants
n=35 Participants

PRIMARY outcome

Timeframe: Day 1, Week 24

Population: The ITT Population consisted of all randomized subjects who received at least one injection of study medication. Missing data up to Week 24 were imputed using the last observation carried forward (LOCF) approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement.

Change in HbA1c from baseline (Day 1) to Week 24 \[Week 24 - Baseline\].

Outcome measures

Outcome measures
Measure
Exenatide Once Weekly
n=126 Participants
Subcutaneous injection of 2 mg exenatide, once a week
Exenatide Twice Daily
n=116 Participants
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 20 weeks)
Exenatide Once Weekly No SU
Subjects with subcutaneous injection of 2 mg exenatide, once a week not using concomitant SU at screening
Exenatide Twice Daily No SU
Subjects with subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 20 weeks) not using concomitant SU at screening
Change in HbA1c From Baseline to Week 24
-1.57 percentage of total hemoglobin
Standard Error 0.104 • Interval -1.77 to -1.36
-0.90 percentage of total hemoglobin
Standard Error 0.110 • Interval -1.12 to -0.69

SECONDARY outcome

Timeframe: Week 24

Population: ITT Population. Missing data up to Week 24 were imputed using LOCF approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement. Subjects without post-baseline measurement were categorized as not achieving goal.

Percentages of subjects achieving HbA1c target value of \<7% at Week 24.

Outcome measures

Outcome measures
Measure
Exenatide Once Weekly
n=129 Participants
Subcutaneous injection of 2 mg exenatide, once a week
Exenatide Twice Daily
n=123 Participants
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 20 weeks)
Exenatide Once Weekly No SU
Subjects with subcutaneous injection of 2 mg exenatide, once a week not using concomitant SU at screening
Exenatide Twice Daily No SU
Subjects with subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 20 weeks) not using concomitant SU at screening
Percentage of Subjects Achieving HbA1c Target of <7%
58.1 percentage of subjects
30.1 percentage of subjects

SECONDARY outcome

Timeframe: Week 24

Population: ITT Population. Missing data up to Week 24 were imputed using LOCF approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement. Subjects without post-baseline measurement were categorized as not achieving goal.

Percentages of subjects achieving HbA1c target values of \<=6.5% at Week 24.

Outcome measures

Outcome measures
Measure
Exenatide Once Weekly
n=129 Participants
Subcutaneous injection of 2 mg exenatide, once a week
Exenatide Twice Daily
n=123 Participants
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 20 weeks)
Exenatide Once Weekly No SU
Subjects with subcutaneous injection of 2 mg exenatide, once a week not using concomitant SU at screening
Exenatide Twice Daily No SU
Subjects with subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 20 weeks) not using concomitant SU at screening
Percentage of Subjects Achieving HbA1c Target of <=6.5%
41.1 percentage of subjects
16.3 percentage of subjects

SECONDARY outcome

Timeframe: Day 1, Week 24

Population: ITT Population. Missing data up to Week 24 were imputed using LOCF approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement.

Change in fasting plasma glucose from baseline (Day 1) to Week 24.

Outcome measures

Outcome measures
Measure
Exenatide Once Weekly
n=127 Participants
Subcutaneous injection of 2 mg exenatide, once a week
Exenatide Twice Daily
n=117 Participants
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 20 weeks)
Exenatide Once Weekly No SU
Subjects with subcutaneous injection of 2 mg exenatide, once a week not using concomitant SU at screening
Exenatide Twice Daily No SU
Subjects with subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 20 weeks) not using concomitant SU at screening
Change in Fasting Plasma Glucose From Baseline to Week 24
-25.1 mg/dL
Standard Error 4.32 • Interval -33.6 to -16.6
-4.6 mg/dL
Standard Error 4.50 • Interval -13.5 to 4.2

SECONDARY outcome

Timeframe: Week 24

Population: ITT Population. Missing data up to Week 24 were imputed using LOCF approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement. Subjects without post-baseline measurement were categorized as not achieving goal.

Percentages of subjects achieving fasting plasma glucose target of \<=126 mg/dL at Week 24.

Outcome measures

Outcome measures
Measure
Exenatide Once Weekly
n=129 Participants
Subcutaneous injection of 2 mg exenatide, once a week
Exenatide Twice Daily
n=123 Participants
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 20 weeks)
Exenatide Once Weekly No SU
Subjects with subcutaneous injection of 2 mg exenatide, once a week not using concomitant SU at screening
Exenatide Twice Daily No SU
Subjects with subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 20 weeks) not using concomitant SU at screening
Percentage of Subjects Achieving Fasting Plasma Glucose Target of <=126 mg/dL
50.4 percentage of subjects
30.9 percentage of subjects

SECONDARY outcome

Timeframe: Day 1, Week 24

Population: ITT Population. Missing data up to Week 24 were imputed using LOCF approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement.

Change in body weight from baseline (Day 1) to Week 24.

Outcome measures

Outcome measures
Measure
Exenatide Once Weekly
n=128 Participants
Subcutaneous injection of 2 mg exenatide, once a week
Exenatide Twice Daily
n=120 Participants
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 20 weeks)
Exenatide Once Weekly No SU
Subjects with subcutaneous injection of 2 mg exenatide, once a week not using concomitant SU at screening
Exenatide Twice Daily No SU
Subjects with subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 20 weeks) not using concomitant SU at screening
Change in Body Weight From Baseline to Week 24
-2.33 kg
Standard Error 0.369 • Interval -3.05 to -1.6
-1.37 kg
Standard Error 0.386 • Interval -2.13 to -0.61

SECONDARY outcome

Timeframe: Day 1, Week 24

Population: ITT Population. Missing data up to Week 24 were imputed using LOCF approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement.

Change in systolic blood pressure from baseline (Day 1) to Week 24.

Outcome measures

Outcome measures
Measure
Exenatide Once Weekly
n=128 Participants
Subcutaneous injection of 2 mg exenatide, once a week
Exenatide Twice Daily
n=120 Participants
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 20 weeks)
Exenatide Once Weekly No SU
Subjects with subcutaneous injection of 2 mg exenatide, once a week not using concomitant SU at screening
Exenatide Twice Daily No SU
Subjects with subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 20 weeks) not using concomitant SU at screening
Change in Sitting Systolic Blood Pressure From Baseline to Week 24
-2.9 mmHg
Standard Error 1.13 • Interval -5.2 to -0.7
-1.2 mmHg
Standard Error 1.19 • Interval -3.5 to 1.2

SECONDARY outcome

Timeframe: Day 1, Week 24

Population: ITT Population. Missing data up to Week 24 were imputed using LOCF approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement.

Change in diastolic blood pressure from baseline (Day 1) to Week 24.

Outcome measures

Outcome measures
Measure
Exenatide Once Weekly
n=128 Participants
Subcutaneous injection of 2 mg exenatide, once a week
Exenatide Twice Daily
n=120 Participants
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 20 weeks)
Exenatide Once Weekly No SU
Subjects with subcutaneous injection of 2 mg exenatide, once a week not using concomitant SU at screening
Exenatide Twice Daily No SU
Subjects with subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 20 weeks) not using concomitant SU at screening
Change in Sitting Diastolic Blood Pressure From Baseline to Week 24
0.2 mmHg
Standard Error 0.74 • Interval -1.3 to 1.6
-0.1 mmHg
Standard Error 0.78 • Interval -1.7 to 1.4

SECONDARY outcome

Timeframe: Day 1, Week 24

Population: ITT Population. Missing data up to Week 24 were imputed using LOCF approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement.

Change in total cholesterol from baseline (Day 1) to Week 24.

Outcome measures

Outcome measures
Measure
Exenatide Once Weekly
n=119 Participants
Subcutaneous injection of 2 mg exenatide, once a week
Exenatide Twice Daily
n=104 Participants
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 20 weeks)
Exenatide Once Weekly No SU
Subjects with subcutaneous injection of 2 mg exenatide, once a week not using concomitant SU at screening
Exenatide Twice Daily No SU
Subjects with subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 20 weeks) not using concomitant SU at screening
Change in Total Cholesterol From Baseline to Week 24
-15.4 mg/dL
Standard Error 2.61 • Interval -20.5 to -10.2
0.6 mg/dL
Standard Error 2.79 • Interval -4.9 to 6.1

SECONDARY outcome

Timeframe: Day 1, Week 24

Population: ITT Population. Missing data up to Week 24 were imputed using LOCF approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement.

Change in HDL from baseline (Day 1) to Week 24.

Outcome measures

Outcome measures
Measure
Exenatide Once Weekly
n=119 Participants
Subcutaneous injection of 2 mg exenatide, once a week
Exenatide Twice Daily
n=104 Participants
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 20 weeks)
Exenatide Once Weekly No SU
Subjects with subcutaneous injection of 2 mg exenatide, once a week not using concomitant SU at screening
Exenatide Twice Daily No SU
Subjects with subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 20 weeks) not using concomitant SU at screening
Change in High-density Lipoprotein (HDL) From Baseline to Week 24
0.0 mg/dL
Standard Error 0.60 • Interval -1.2 to 1.2
1.3 mg/dL
Standard Error 0.64 • Interval 0.0 to 2.5

SECONDARY outcome

Timeframe: Day 1, Week 24

Population: ITT Population. Missing data up to Week 24 were imputed using LOCF approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement.

Ratio of triglycerides (measured in mg/dL) at Week 24 to baseline (Day 1). Log (Postbaseline Triglycerides) - log (Baseline Triglycerides); change from baseline to endpoint is presented as ratio of endpoint to baseline.

Outcome measures

Outcome measures
Measure
Exenatide Once Weekly
n=119 Participants
Subcutaneous injection of 2 mg exenatide, once a week
Exenatide Twice Daily
n=104 Participants
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 20 weeks)
Exenatide Once Weekly No SU
Subjects with subcutaneous injection of 2 mg exenatide, once a week not using concomitant SU at screening
Exenatide Twice Daily No SU
Subjects with subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 20 weeks) not using concomitant SU at screening
Ratio of Triglycerides at Week 24 to Baseline
0.94 ratio
Standard Error 0.032 • Interval 0.88 to 1.0
0.99 ratio
Standard Error 0.036 • Interval 0.92 to 1.06

SECONDARY outcome

Timeframe: Day 1 to Week 24

Population: ITT Population. Analysis was done for SU ITT patients (ITT patients taking SU) and Non-SU ITT patients separately.

The major hypoglycemia category included events that, in the judgment of the investigator or physician, resulted in loss of consciousness, seizure, coma, or other change in mental status consistent with neuroglycopenia, in which symptoms resolved after administration of intramuscular glucagon or intravenous glucose, required third-party assistance, and was accompanied by a blood glucose concentration of less than 54 mg/dL prior to treatment, whether or not symptoms of hypoglycemia were perceived by the subject.

Outcome measures

Outcome measures
Measure
Exenatide Once Weekly
n=40 Participants
Subcutaneous injection of 2 mg exenatide, once a week
Exenatide Twice Daily
n=34 Participants
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 20 weeks)
Exenatide Once Weekly No SU
n=89 Participants
Subjects with subcutaneous injection of 2 mg exenatide, once a week not using concomitant SU at screening
Exenatide Twice Daily No SU
n=89 Participants
Subjects with subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 20 weeks) not using concomitant SU at screening
Assessment on Event Rate of Treatment-emergent Major Hypoglycemic Events
0.00 rate per subject-year
Standard Error 0.000
0.00 rate per subject-year
Standard Error 0.000
0.00 rate per subject-year
Standard Error 0.000
0.00 rate per subject-year
Standard Error 0.000

SECONDARY outcome

Timeframe: Day 1 to Week 24

Population: ITT Population. Analysis was done for SU ITT patients (ITT patients taking SU) and Non-SU ITT patients separately.

The minor hypoglycemia category included events in which symptoms consistent with hypoglycemia were accompanied by a blood glucose concentration of less than 54 mg/dL prior to treatment and not classified as major hypoglycemia.

Outcome measures

Outcome measures
Measure
Exenatide Once Weekly
n=40 Participants
Subcutaneous injection of 2 mg exenatide, once a week
Exenatide Twice Daily
n=34 Participants
Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 20 weeks)
Exenatide Once Weekly No SU
n=89 Participants
Subjects with subcutaneous injection of 2 mg exenatide, once a week not using concomitant SU at screening
Exenatide Twice Daily No SU
n=89 Participants
Subjects with subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 20 weeks) not using concomitant SU at screening
Assessment on Event Rate of Treatment-emergent Minor Hypoglycemic Events
0.75 rate per subject-year
Standard Error 0.217
0.31 rate per subject-year
Standard Error 0.153
0.00 rate per subject-year
Standard Error 0.000
0.00 rate per subject-year
Standard Error 0.000

Adverse Events

Exenatide Once Weekly

Serious events: 3 serious events
Other events: 44 other events
Deaths: 0 deaths

Exenatide Twice Daily

Serious events: 5 serious events
Other events: 58 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Exenatide Once Weekly
n=129 participants at risk
Subcutaneous injection of 2 mg exenatide, once a week
Exenatide Twice Daily
n=123 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 20 weeks)
Renal and urinary disorders
Calculus ureteric
0.78%
1/129
0.00%
0/123
Infections and infestations
Cellulitis
0.78%
1/129
0.00%
0/123
Gastrointestinal disorders
Pancreatitis
0.78%
1/129
0.00%
0/123
General disorders
Chest pain
0.00%
0/129
0.81%
1/123
Hepatobiliary disorders
Cholecystitis
0.00%
0/129
0.81%
1/123
Hepatobiliary disorders
Cholelithiasis
0.00%
0/129
0.81%
1/123
Cardiac disorders
Coronary artery disease
0.00%
0/129
0.81%
1/123
Gastrointestinal disorders
Gastrointestinal haemorrhage
0.00%
0/129
0.81%
1/123
Cardiac disorders
Myocardial infarction
0.00%
0/129
0.81%
1/123
Cardiac disorders
Myocardial ischaemia
0.00%
0/129
0.81%
1/123

Other adverse events

Other adverse events
Measure
Exenatide Once Weekly
n=129 participants at risk
Subcutaneous injection of 2 mg exenatide, once a week
Exenatide Twice Daily
n=123 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 20 weeks)
Gastrointestinal disorders
Nausea
14.0%
18/129
35.0%
43/123
Gastrointestinal disorders
Diarrhoea
9.3%
12/129
4.1%
5/123
Infections and infestations
Upper respiratory tract infection
7.0%
9/129
4.1%
5/123
General disorders
Injection site erythema
5.4%
7/129
2.4%
3/123
Nervous system disorders
Headache
4.7%
6/129
8.1%
10/123
Gastrointestinal disorders
Vomiting
4.7%
6/129
8.9%
11/123
Nervous system disorders
Dizziness
2.3%
3/129
6.5%
8/123

Additional Information

Peter Ohman, Medical Science Director

AstraZeneca

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place

Restriction type: LTE60