Diabetes Mellitus, Type 2
Conditions
Brief summary
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. To examine the long-term (52 weeks of treatment) safety and effect on glucose control of exenatide suspension administered once weekly in subjects with type 2 diabetes mellitus.
Interventions
Exenatide suspension 2 mg weekly subcutaneous injection
5 mcg twice daily for 4 weeks followed by 10 mcg twice daily for 24 weeks
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* At least 18 years old * Diagnosed with type 2 diabetes mellitus * HbA1c 7.1 to 11%, inclusive, at screening * Fasting plasma glucose \<280 mg/dL (15.5 mmol/L) * Body mass index (BMI) \<=45 kg/m2, inclusive, at screening * Treated with diet and exercise or a stable regimen of metformin, sulfonylurea, pioglitazone or any 2 of these agents
Exclusion criteria
* History of pancreatitis or triglycerides \>=500 mg/dL * Medullary carcinoma or multiple endocrine neoplasia (MEN2) or a family history of either * Active cardiovascular disease * Presence of congestive heart failure * Liver disease * History of severe gastrointestinal diseases * Repeated severe hypoglycemia within the last 6 months * Any previous use of exenatide or other glucagon-like peptide-1 (GLP-1 ) analog * Dipeptidyl peptidase-4 (DPP-4) inhibitor use in the last 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c (Glycosylated Hemoglobin) From Baseline to Week 28 | Baseline to Week 28 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Achieving HbA1c <7% at Week 28 | Baseline to Week 28 | Percentage of subjects achieving HbA1c \<7% at Week 28/Study Termination |
| Change in Fasting Plasma Glucose Concentrations From Baseline to Week 28 | Baseline to Week 28 | Change in fasting plasma glucose concentrations from baseline to Week 28/Study Termination |
| Change in Body Weight (kg) From Baseline to Week 28 | Baseline to Week 28 | Change in body weight (kg) from baseline to Week 28/Study Termination. |
| Change in 2-hour Postprandial Glucose Concentrations From Baseline to Week 16 | Baseline to Week 16 | Change in 2-hour postprandial glucose concentrations from baseline to Week 16. |
Countries
United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Experimental: Exenatide QWS Suspension Exenatide suspension 2 mg weekly subcutaneous injection 52 weeks (28 weeks plus an additional 24 weeks) | 229 |
| Active Comparator: Exenatide 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 | 146 |
| Total | 375 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative | 0 | 2 |
| Overall Study | Adverse Event | 7 | 10 |
| Overall Study | Investigator decision | 1 | 4 |
| Overall Study | Loss of glucose control | 1 | 0 |
| Overall Study | Lost to Follow-up | 12 | 11 |
| Overall Study | Protocol Violation | 2 | 1 |
| Overall Study | Withdrawal by Subject | 33 | 18 |
Baseline characteristics
| Characteristic | Experimental: Exenatide QWS Suspension | Active Comparator: Exenatide BID | Total |
|---|---|---|---|
| Age, Continuous | 55.6 Years STANDARD_DEVIATION 9.98 | 56.5 Years STANDARD_DEVIATION 9.04 | 56.0 Years STANDARD_DEVIATION 9.62 |
| Age, Customized <65 years | 182 Participants | 118 Participants | 300 Participants |
| Age, Customized >=65 years | 47 Participants | 28 Participants | 75 Participants |
| Baseline HbA1c | 8.47 Percentage of total hemoglobin STANDARD_DEVIATION 1.047 | 8.51 Percentage of total hemoglobin STANDARD_DEVIATION 1.004 | 8.48 Percentage of total hemoglobin STANDARD_DEVIATION 1.029 |
| Duration of diabetes | 8.55 Years STANDARD_DEVIATION 6.249 | 8.47 Years STANDARD_DEVIATION 5.961 | 8.52 Years STANDARD_DEVIATION 6.132 |
| Fasting plasma glucose | 180.92 mg/dL STANDARD_DEVIATION 44.538 | 183.77 mg/dL STANDARD_DEVIATION 46.904 | 182.03 mg/dL STANDARD_DEVIATION 45.437 |
| HbA1c Stratum <9.0% | 159 Number of subjects | 97 Number of subjects | 256 Number of subjects |
| HbA1c Stratum >=9.0% | 68 Number of subjects | 49 Number of subjects | 117 Number of subjects |
| HbA1c Stratum Not Recorded | 2 Number of subjects | 0 Number of subjects | 2 Number of subjects |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants | 3 Participants | 5 Participants |
| Race/Ethnicity, Customized Asian | 17 Participants | 8 Participants | 25 Participants |
| Race/Ethnicity, Customized Black or African American | 38 Participants | 23 Participants | 61 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 54 Participants | 34 Participants | 88 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 174 Participants | 112 Participants | 286 Participants |
| Race/Ethnicity, Customized Other | 3 Participants | 2 Participants | 5 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 168 Participants | 110 Participants | 278 Participants |
| Sex: Female, Male Female | 81 Participants | 54 Participants | 135 Participants |
| Sex: Female, Male Male | 148 Participants | 92 Participants | 240 Participants |
| Weight | 214.52 lbs STANDARD_DEVIATION 49.788 | 213.19 lbs STANDARD_DEVIATION 40.834 | 214.00 lbs STANDARD_DEVIATION 46.445 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 121 / 229 | 94 / 146 |
| serious Total, serious adverse events | 12 / 229 | 17 / 146 |
Outcome results
Primary
Change in HbA1c (Glycosylated Hemoglobin) From Baseline to Week 28
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.
Time frame: Baseline to Week 28
Population: Modified Intent-to-Treat: Subjects who were randomized and received at least one dose of study drug
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Experimental: Exenatide QWS Suspension | Change in HbA1c (Glycosylated Hemoglobin) From Baseline to Week 28 | -1.39 Percentage of total hemoglobin | Standard Error 0.093 |
| Active Comparator: Exenatide BID | Change in HbA1c (Glycosylated Hemoglobin) From Baseline to Week 28 | -1.02 Percentage of total hemoglobin | Standard Error 0.1147 |
p-value: 0.007295% CI: [-0.63, -0.1]Mixed model for repeated measure (MMRM)
Secondary
Change in 2-hour Postprandial Glucose Concentrations From Baseline to Week 16
Change in 2-hour postprandial glucose concentrations from baseline to Week 16.
Time frame: Baseline to Week 16
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Experimental: Exenatide QWS Suspension | Change in 2-hour Postprandial Glucose Concentrations From Baseline to Week 16 | -87.00 mg/dL | Standard Error 12.8374 |
| Active Comparator: Exenatide BID | Change in 2-hour Postprandial Glucose Concentrations From Baseline to Week 16 | -113.74 mg/dL | Standard Error 14.8042 |
p-value: 0.098595% CI: [-5.16, 58.64]Cochran-Mantel-Haenszel
Secondary
Change in Body Weight (kg) From Baseline to Week 28
Change in body weight (kg) from baseline to Week 28/Study Termination.
Time frame: Baseline to Week 28
Population: Modified Intent-to-Treat: Subjects who were randomized and received at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Experimental: Exenatide QWS Suspension | Change in Body Weight (kg) From Baseline to Week 28 | -1.49 kg | Standard Error 0.2842 |
| Active Comparator: Exenatide BID | Change in Body Weight (kg) From Baseline to Week 28 | -1.89 kg | Standard Error 0.364 |
p-value: 0.374495% CI: [-0.48, 1.28]Cochran-Mantel-Haenszel
Secondary
Change in Fasting Plasma Glucose Concentrations From Baseline to Week 28
Change in fasting plasma glucose concentrations from baseline to Week 28/Study Termination
Time frame: Baseline to Week 28
Population: Modified Intent-to-Treat: Subjects who were randomized and received at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Experimental: Exenatide QWS Suspension | Change in Fasting Plasma Glucose Concentrations From Baseline to Week 28 | -32.7 mg/dL | Standard Error 3.906 |
| Active Comparator: Exenatide BID | Change in Fasting Plasma Glucose Concentrations From Baseline to Week 28 | -22.5 mg/dL | Standard Error 4.917 |
p-value: 0.165695% CI: [-21.7, 1.3]Cochran-Mantel-Haenszel
Secondary
Percentage of Subjects Achieving HbA1c <7% at Week 28
Percentage of subjects achieving HbA1c \<7% at Week 28/Study Termination
Time frame: Baseline to Week 28
Population: Modified Intent-to-Treat: Subjects who were randomized and received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Experimental: Exenatide QWS Suspension | Percentage of Subjects Achieving HbA1c <7% at Week 28 | Baseline No | 95.2 Percentage of subjects |
| Experimental: Exenatide QWS Suspension | Percentage of Subjects Achieving HbA1c <7% at Week 28 | Week 28 No | 49.8 Percentage of subjects |
| Experimental: Exenatide QWS Suspension | Percentage of Subjects Achieving HbA1c <7% at Week 28 | Week 28 Yes | 49.3 Percentage of subjects |
| Experimental: Exenatide QWS Suspension | Percentage of Subjects Achieving HbA1c <7% at Week 28 | Baseline missing | 0.9 Percentage of subjects |
| Experimental: Exenatide QWS Suspension | Percentage of Subjects Achieving HbA1c <7% at Week 28 | Baseline Yes | 3.9 Percentage of subjects |
| Active Comparator: Exenatide BID | Percentage of Subjects Achieving HbA1c <7% at Week 28 | Baseline missing | 0 Percentage of subjects |
| Active Comparator: Exenatide BID | Percentage of Subjects Achieving HbA1c <7% at Week 28 | Baseline Yes | 1.4 Percentage of subjects |
| Active Comparator: Exenatide BID | Percentage of Subjects Achieving HbA1c <7% at Week 28 | Baseline No | 98.6 Percentage of subjects |
| Active Comparator: Exenatide BID | Percentage of Subjects Achieving HbA1c <7% at Week 28 | Week 28 Yes | 43.2 Percentage of subjects |
| Active Comparator: Exenatide BID | Percentage of Subjects Achieving HbA1c <7% at Week 28 | Week 28 No | 56.8 Percentage of subjects |
p-value: 0.2247Cochran-Mantel-Haenszel