Type 2 Diabetes
Conditions
Brief summary
A Randomized, Double-blind, Parallel-group Study to Evaluate the Effect of Bydureon Compared with Placebo on 24-hour Glucose Control in Metformin-treated Patients with Type 2 Diabetes.
Detailed description
A Randomized, Double-blind, Parallel-group Study to Evaluate the Effect of Bydureon Compared with Placebo on 24-hour Glucose Control in 110 Metformin-treated Patients with Type 2 Diabetes
Interventions
DRUGBydureon
Once weekly injection of 2mg bydureon (extended release exenatide) for 10 weeks.
DRUGPlacebo
Placebo
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Type 2 diabetes mellitus (T2DM) treated with stable dose of metformin \> or = to 1500mg/day as monotherapy for at least 8 weeks * Hemoglobin A1c (HbA1c) 7% to 10% at screening * Body mass index (BMI) \< or = to 45 kg/m2
Exclusion criteria
* History of taking antihyperglycemic therapy other than metformin or metformin extended release (XR) during the 8 weeks prior to screening * History of taking a dipeptidyl peptidase-4 (DPP-4) inhibitor or pramlintide during 12 weeks prior to screening * History of potent, inhaled or intrapulmonary steroids 3 months prior to screening or during the study * History of prescription or over the counter weight loss medication during 3 months prior to screening * Previous exposure to exenatide or any glucagon-like peptide-1 (GLP-1) receptor agonist during 6 months prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in 24-hour Mean Weighted Glucose | Day 27/28 | Change in 24-hour mean weighted glucose from baseline (Day -1/1) to Day 6 of Week 4 (Day 27/28) and to Day 6 of Week 10 (Day 69/70). |
Secondary
| Measure | Time frame |
|---|---|
| Change in 24-hour Mean Weighted Glucose Between Day 1 of Week 10 (Day 64/65) and Day 6 of Week 10 (Day 69/70) Within Each EQW-treated Patient | Day 64/65 |
| Change From Baseline (Day1) to Day 70 and Day 22 in FPG | Day 22/Day70 |
| Change From Baseline (Day -1) to Day 64 and Day 22 in 2- Hour Mean Weighted PPG (After the Breakfast Meal) | Day 22 and Day 64 |
| Average of Change in 24-hour Mean Weighted Glucose From Baseline to Week 4 and Baseline to Week 10 | Week 4 and Week 10 |
| Change in HbA1c From Baseline to Day 22 and Baseline to Day 70 | Day 22 and Day 70 |
Countries
United States
Participant flow
Pre-assignment details
239 subjects were screened in order to randomize 117 subjects; however, 116 subjects were included in the modified intent to treat population, which consisted of all randomized patients who received at least one dose of randomized study drug.
Participants by arm
| Arm | Count |
|---|---|
| Once Weekly (EQW) + Met Bydureon EQW + Metformin XR 1500-2000 mg | 60 |
| Placebo + Met Placebo + Metformin 1500 + 2000 mg | 56 |
| Total | 116 |
Baseline characteristics
| Characteristic | Once Weekly (EQW) + Met | Placebo + Met | Total |
|---|---|---|---|
| Age, Continuous | 55 Years STANDARD_DEVIATION 10.63 | 56 Years STANDARD_DEVIATION 9.8 | 55.6 Years STANDARD_DEVIATION 10.21 |
| Gender Female | 27 Participants | 24 Participants | 51 Participants |
| Gender Male | 33 Participants | 32 Participants | 65 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 35 / 60 | 26 / 56 |
| serious Total, serious adverse events | 4 / 60 | 1 / 56 |
Outcome results
Primary
Change in 24-hour Mean Weighted Glucose
Change in 24-hour mean weighted glucose from baseline (Day -1/1) to Day 6 of Week 4 (Day 27/28) and to Day 6 of Week 10 (Day 69/70).
Time frame: Day 27/28
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EQW + Met | Change in 24-hour Mean Weighted Glucose | Baseline (Day -1/1) | 185.7 (mg/dL) | Standard Deviation 41.99 |
| EQW + Met | Change in 24-hour Mean Weighted Glucose | Day 27/28 | 158.3 (mg/dL) | Standard Deviation 35.72 |
| EQW + Met | Change in 24-hour Mean Weighted Glucose | Change from Baseline to Day 27/28 | -26.0 (mg/dL) | Standard Deviation 3.58 |
| EQW + Met | Change in 24-hour Mean Weighted Glucose | Change from Baseline to Day 69/70 | -30.8 (mg/dL) | Standard Deviation 4.54 |
| Placebo + Met | Change in 24-hour Mean Weighted Glucose | Change from Baseline to Day 69/70 | -3.0 (mg/dL) | Standard Deviation 4.78 |
| Placebo + Met | Change in 24-hour Mean Weighted Glucose | Baseline (Day -1/1) | 183.8 (mg/dL) | Standard Deviation 42.59 |
| Placebo + Met | Change in 24-hour Mean Weighted Glucose | Change from Baseline to Day 27/28 | -5.3 (mg/dL) | Standard Deviation 3.85 |
| Placebo + Met | Change in 24-hour Mean Weighted Glucose | Day 27/28 | 176.9 (mg/dL) | Standard Deviation 44.03 |
p-value: <0.001Mixed Models Analysis
Secondary
Average of Change in 24-hour Mean Weighted Glucose From Baseline to Week 4 and Baseline to Week 10
Time frame: Week 4 and Week 10
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| EQW + Met | Average of Change in 24-hour Mean Weighted Glucose From Baseline to Week 4 and Baseline to Week 10 | Change in %: 70 </= PG </=180 baseline to week 4 | 15.8 % times patients had specific CGM/24-hr | Standard Error 2.37 |
| EQW + Met | Average of Change in 24-hour Mean Weighted Glucose From Baseline to Week 4 and Baseline to Week 10 | Change in times (%): PG >180 baseline to Week 4 | -16.2 % times patients had specific CGM/24-hr | Standard Error 2.37 |
| EQW + Met | Average of Change in 24-hour Mean Weighted Glucose From Baseline to Week 4 and Baseline to Week 10 | Change in times (%): PG <70 baseline to Week 10 | 0.5 % times patients had specific CGM/24-hr | Standard Error 0.21 |
| EQW + Met | Average of Change in 24-hour Mean Weighted Glucose From Baseline to Week 4 and Baseline to Week 10 | Change in times (%): PG >180 baseline to Week 10 | -22.0 % times patients had specific CGM/24-hr | Standard Error 3.04 |
| EQW + Met | Average of Change in 24-hour Mean Weighted Glucose From Baseline to Week 4 and Baseline to Week 10 | Change in %: 70 </= PG </=180 baseline to week 10 | 21.4 % times patients had specific CGM/24-hr | Standard Error 2.99 |
| EQW + Met | Average of Change in 24-hour Mean Weighted Glucose From Baseline to Week 4 and Baseline to Week 10 | Change in times(%): PG<70 baseline to Week 4 | 0.5 % times patients had specific CGM/24-hr | Standard Error 0.19 |
| Placebo + Met | Average of Change in 24-hour Mean Weighted Glucose From Baseline to Week 4 and Baseline to Week 10 | Change in %: 70 </= PG </=180 baseline to week 10 | 1.3 % times patients had specific CGM/24-hr | Standard Error 3.09 |
| Placebo + Met | Average of Change in 24-hour Mean Weighted Glucose From Baseline to Week 4 and Baseline to Week 10 | Change in times (%): PG <70 baseline to Week 10 | 0.1 % times patients had specific CGM/24-hr | Standard Error 0.21 |
| Placebo + Met | Average of Change in 24-hour Mean Weighted Glucose From Baseline to Week 4 and Baseline to Week 10 | Change in %: 70 </= PG </=180 baseline to week 4 | 4.1 % times patients had specific CGM/24-hr | Standard Error 2.46 |
| Placebo + Met | Average of Change in 24-hour Mean Weighted Glucose From Baseline to Week 4 and Baseline to Week 10 | Change in times(%): PG<70 baseline to Week 4 | 0.2 % times patients had specific CGM/24-hr | Standard Error 0.19 |
| Placebo + Met | Average of Change in 24-hour Mean Weighted Glucose From Baseline to Week 4 and Baseline to Week 10 | Change in times (%): PG >180 baseline to Week 4 | -4.3 % times patients had specific CGM/24-hr | Standard Error 2.47 |
| Placebo + Met | Average of Change in 24-hour Mean Weighted Glucose From Baseline to Week 4 and Baseline to Week 10 | Change in times (%): PG >180 baseline to Week 10 | -1.4 % times patients had specific CGM/24-hr | Standard Error 3.14 |
Secondary
Average of Change in 24-hour Mean Weighted Glucose From Baseline to Week 4 and Baseline to Week 10
Time frame: Week 4 and Week 10
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| EQW + Met | Average of Change in 24-hour Mean Weighted Glucose From Baseline to Week 4 and Baseline to Week 10 | Change in mean weighted glucose baseline to Week 4 | -4.5 mg/dL | Standard Error 1.09 |
| EQW + Met | Average of Change in 24-hour Mean Weighted Glucose From Baseline to Week 4 and Baseline to Week 10 | Change in mean weighted glucose baseline - Week 10 | -6.3 mg/dL | Standard Error 1.31 |
| EQW + Met | Average of Change in 24-hour Mean Weighted Glucose From Baseline to Week 4 and Baseline to Week 10 | Change in MAGE (mg/dL) from baseline to Week 4 | -8.2 mg/dL | Standard Error 3.13 |
| EQW + Met | Average of Change in 24-hour Mean Weighted Glucose From Baseline to Week 4 and Baseline to Week 10 | Change in MAGE (mg/dL) from baseline to Week 10 | -15.2 mg/dL | Standard Error 3.51 |
| Placebo + Met | Average of Change in 24-hour Mean Weighted Glucose From Baseline to Week 4 and Baseline to Week 10 | Change in MAGE (mg/dL) from baseline to Week 10 | 2.9 mg/dL | Standard Error 3.62 |
| Placebo + Met | Average of Change in 24-hour Mean Weighted Glucose From Baseline to Week 4 and Baseline to Week 10 | Change in mean weighted glucose baseline to Week 4 | -1.8 mg/dL | Standard Error 1.13 |
| Placebo + Met | Average of Change in 24-hour Mean Weighted Glucose From Baseline to Week 4 and Baseline to Week 10 | Change in MAGE (mg/dL) from baseline to Week 4 | -3.8 mg/dL | Standard Error 3.25 |
| Placebo + Met | Average of Change in 24-hour Mean Weighted Glucose From Baseline to Week 4 and Baseline to Week 10 | Change in mean weighted glucose baseline - Week 10 | 0.7 mg/dL | Standard Error 1.36 |
Secondary
Change From Baseline (Day -1) to Day 64 and Day 22 in 2- Hour Mean Weighted PPG (After the Breakfast Meal)
Time frame: Day 22 and Day 64
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| EQW + Met | Change From Baseline (Day -1) to Day 64 and Day 22 in 2- Hour Mean Weighted PPG (After the Breakfast Meal) | Baseline to Day 22 | -32.1 mg/dL | Standard Error 5.3 |
| EQW + Met | Change From Baseline (Day -1) to Day 64 and Day 22 in 2- Hour Mean Weighted PPG (After the Breakfast Meal) | Baseline to Day 64 | -44.4 mg/dL | Standard Error 5.62 |
| Placebo + Met | Change From Baseline (Day -1) to Day 64 and Day 22 in 2- Hour Mean Weighted PPG (After the Breakfast Meal) | Baseline to Day 22 | -2.0 mg/dL | Standard Error 5.51 |
| Placebo + Met | Change From Baseline (Day -1) to Day 64 and Day 22 in 2- Hour Mean Weighted PPG (After the Breakfast Meal) | Baseline to Day 64 | -6.0 mg/dL | Standard Error 6.12 |
Secondary
Change From Baseline (Day1) to Day 70 and Day 22 in FPG
Time frame: Day 22/Day70
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| EQW + Met | Change From Baseline (Day1) to Day 70 and Day 22 in FPG | Baseline to Day 22 | -29.6 mg/dL | Standard Error 4.85 |
| EQW + Met | Change From Baseline (Day1) to Day 70 and Day 22 in FPG | Baseline to Day 70 | -41.9 mg/dL | Standard Error 5.21 |
| Placebo + Met | Change From Baseline (Day1) to Day 70 and Day 22 in FPG | Baseline to Day 22 | -1.9 mg/dL | Standard Error 4.99 |
| Placebo + Met | Change From Baseline (Day1) to Day 70 and Day 22 in FPG | Baseline to Day 70 | -5.0 mg/dL | Standard Error 5.53 |
Secondary
Change in 24-hour Mean Weighted Glucose Between Day 1 of Week 10 (Day 64/65) and Day 6 of Week 10 (Day 69/70) Within Each EQW-treated Patient
Time frame: Day 64/65
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| EQW + Met | Change in 24-hour Mean Weighted Glucose Between Day 1 of Week 10 (Day 64/65) and Day 6 of Week 10 (Day 69/70) Within Each EQW-treated Patient | 5.2 mg/dL | Standard Error 3.46 |
| Placebo + Met | Change in 24-hour Mean Weighted Glucose Between Day 1 of Week 10 (Day 64/65) and Day 6 of Week 10 (Day 69/70) Within Each EQW-treated Patient | -6.9 mg/dL | Standard Error 3.68 |
Secondary
Change in HbA1c From Baseline to Day 22 and Baseline to Day 70
Time frame: Day 22 and Day 70
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| EQW + Met | Change in HbA1c From Baseline to Day 22 and Baseline to Day 70 | Change from baseline to Day 22 | -0.30 % Alc | Standard Error 0.045 |
| EQW + Met | Change in HbA1c From Baseline to Day 22 and Baseline to Day 70 | Change from baseline to Day 70 | -0.92 % Alc | Standard Error 0.102 |
| Placebo + Met | Change in HbA1c From Baseline to Day 22 and Baseline to Day 70 | Change from baseline to Day 22 | -0.10 % Alc | Standard Error 0.047 |
| Placebo + Met | Change in HbA1c From Baseline to Day 22 and Baseline to Day 70 | Change from baseline to Day 70 | -0.20 % Alc | Standard Error 0.108 |