Type 2 Diabetes Mellitus
Conditions
Keywords
exenatide, Byetta, type 2 diabetes, heart rate, Amylin, Lilly
Brief summary
This study will explore the effect of exenatide (given twice a day) versus placebo (given twice a day) treatment on change in mean 24-hour heart rate over a 12 week period of drug exposure in patients with type 2 diabetes.
Interventions
DRUGexenatide
subcutaneous injection, 5mcg or 10mcg, twice a day
DRUGplacebo
subcutaneous injection, volume equivalent to active, twice a day
Sponsors
Eli Lilly and Company
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosed with type 2 diabetes. * Treated with metformin and/or a thiazolidinedione. * HbA1c between 6.5% and 9.5%, inclusive. * Body Mass Index (BMI) \> 25 kg/m\^2 and \< 40 kg/m\^2.
Exclusion criteria
* Have previously received exenatide or glucagon-like peptide-1 analogs. * Have participated in an interventional medical, surgical, or pharmaceutical study (a study in which an experimental, drug, medical, or surgical treatment was given) within 30 days of screening. This criterion includes drugs that have not received regulatory approval for any indication at the time of study entry. * Receiving beta blockers. * Receiving treatment with a drug directly affecting gastrointestinal motility, including but not limited to Reglan® (metoclopramide), Propulsid® (cisapride), and chronic macrolide antibiotics. * Have received treatment with systemic glucocorticoid therapy by oral, intravenous (IV), or intramuscular (IM) route within 6 weeks of screening, or are regularly treated with potent, inhaled intranasal steroids that are known to have a high rate of systemic absorption or bronchodilators. * Have been treated with drugs that promote weight loss (for example, Adipex® \[phentermine\], Acomplia® \[rimonabant\], Xenical® \[orlistat\], Meridia® \[sibutramine\], Acutrim® \[phenylpropanolamine\], or similar over-the-counter medications) within 3 months of screening. * Have been treated for longer than 2 weeks with any of the following excluded medications within 3 months prior to screening: \*Insulin; \*Alpha-glucosidase inhibitors (for example, Glyset® \[miglitol\] or Precose® \[acarbose\]); \*Meglitinides (for example, Prandin® \[repaglinide\] or Starlix® \[nateglinide\]); \*Sulfonylureas (for example, Glucotrol® \[glipizide\] or Micronase® \[glyburide\]); \*Dipeptidyl peptidase IV (DPP-IV) inhibitors (for example, Januvia™ \[sitagliptin\]) * Have donated blood within 60 days of screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean 24-hour Heart Rate From Baseline to Endpoint | 12 weeks | Change from baseline to endpoint in average heart rate measured over 24 hours by an ambulatory blood pressure monitor. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Daytime Heart Rate From Baseline to Endpoint | 12 weeks | Change from baseline to endpoint in daytime heart rate as measured by an ambulatory blood pressure monitor |
| Change in Nighttime (2400-0600) Heart Rate From Baseline to Endpoint | 12 weeks | Change from baseline to endpoint in nighttime (2400-0600) heart rate as measured by an ambulatory blood pressure monitor |
| Change in Mean 24 Hour Systolic Blood Pressure From Baseline to Endpoint | 12 weeks | Change from baseline to endpoint in average systolic blood pressure measured over 24 hours by an ambulatory blood pressure monitor |
| Change in Mean 24 Hour Diastolic Blood Pressure From Baseline to Endpoint | 12 weeks | Change from baseline to endpoint in average diastolic blood pressure measured over 24 hours by an ambulatory blood pressure monitor |
| Change in Hemoglobin A1c (HbA1c) From Baseline to Endpoint | 12 weeks | Change from baseline to endpoint in HbA1c |
Countries
Canada, Netherlands
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Exenatide BID 5mcg exenatide twice daily for 4 weeks, and then 10mcg exenatide twice daily for the remaining 8 weeks of the study. | 28 |
| Placebo Placebo injection twice daily (volume equivalent to the exenatide injection in the experimental arm). | 26 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Loss of Glucose Control | 2 | 0 |
| Overall Study | Subject Decision | 4 | 2 |
Baseline characteristics
| Characteristic | Exenatide BID | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 3 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants | 23 Participants | 46 Participants |
| Age, Continuous | 56.62 years STANDARD_DEVIATION 10.9 | 54.14 years STANDARD_DEVIATION 10.13 | 55.43 years STANDARD_DEVIATION 10.51 |
| Sex: Female, Male Female | 9 Participants | 15 Participants | 24 Participants |
| Sex: Female, Male Male | 19 Participants | 11 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 18 / — | 21 / — |
| serious Total, serious adverse events | 1 / — | 1 / — |
Outcome results
Primary
Change in Mean 24-hour Heart Rate From Baseline to Endpoint
Change from baseline to endpoint in average heart rate measured over 24 hours by an ambulatory blood pressure monitor.
Time frame: 12 weeks
Population: Intent to treat; Last observation carried forward
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide BID | Change in Mean 24-hour Heart Rate From Baseline to Endpoint | Baseline (Week 0) | 74.83 beats per minute | Standard Error 2.04 |
| Exenatide BID | Change in Mean 24-hour Heart Rate From Baseline to Endpoint | Change at endpoint (Week 12) | 2.14 beats per minute | Standard Error 1.39 |
| Placebo | Change in Mean 24-hour Heart Rate From Baseline to Endpoint | Baseline (Week 0) | 74.47 beats per minute | Standard Error 2.08 |
| Placebo | Change in Mean 24-hour Heart Rate From Baseline to Endpoint | Change at endpoint (Week 12) | -0.71 beats per minute | Standard Error 1.42 |
p-value: 0.1585ANCOVA
Secondary
Change in Daytime Heart Rate From Baseline to Endpoint
Change from baseline to endpoint in daytime heart rate as measured by an ambulatory blood pressure monitor
Time frame: 12 weeks
Population: Intent to treat; Last observation carried forward
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide BID | Change in Daytime Heart Rate From Baseline to Endpoint | Change at endpoint (Week 12) | 2.35 beats per minute | Standard Error 1.59 |
| Exenatide BID | Change in Daytime Heart Rate From Baseline to Endpoint | Baseline (Week 0) | 75.97 beats per minute | Standard Error 2.22 |
| Placebo | Change in Daytime Heart Rate From Baseline to Endpoint | Change at endpoint (Week 12) | -0.87 beats per minute | Standard Error 1.62 |
| Placebo | Change in Daytime Heart Rate From Baseline to Endpoint | Baseline (Week 0) | 75.37 beats per minute | Standard Error 2.26 |
p-value: 0.1624ANCOVA
Secondary
Change in Hemoglobin A1c (HbA1c) From Baseline to Endpoint
Change from baseline to endpoint in HbA1c
Time frame: 12 weeks
Population: Intent to treat; Last observation carried forward
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide BID | Change in Hemoglobin A1c (HbA1c) From Baseline to Endpoint | Baseline (Week 0) | 7.50 percent | Standard Error 0.16 |
| Exenatide BID | Change in Hemoglobin A1c (HbA1c) From Baseline to Endpoint | Change at endpoint (Week 12) | -0.15 percent | Standard Error 0.16 |
| Placebo | Change in Hemoglobin A1c (HbA1c) From Baseline to Endpoint | Change at endpoint (Week 12) | 0.12 percent | Standard Error 0.17 |
| Placebo | Change in Hemoglobin A1c (HbA1c) From Baseline to Endpoint | Baseline (Week 0) | 7.11 percent | Standard Error 0.17 |
p-value: 0.26ANCOVA
Secondary
Change in Mean 24 Hour Diastolic Blood Pressure From Baseline to Endpoint
Change from baseline to endpoint in average diastolic blood pressure measured over 24 hours by an ambulatory blood pressure monitor
Time frame: 12 weeks
Population: Intent to treat; Last observation carried forward
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide BID | Change in Mean 24 Hour Diastolic Blood Pressure From Baseline to Endpoint | Baseline (Week 0) | 75.70 mmHg | Standard Error 2.05 |
| Exenatide BID | Change in Mean 24 Hour Diastolic Blood Pressure From Baseline to Endpoint | Change at endpoint (Week 12) | -0.60 mmHg | Standard Error 1.49 |
| Placebo | Change in Mean 24 Hour Diastolic Blood Pressure From Baseline to Endpoint | Baseline (Week 0) | 70.54 mmHg | Standard Error 2.09 |
| Placebo | Change in Mean 24 Hour Diastolic Blood Pressure From Baseline to Endpoint | Change at endpoint (Week 12) | -2.34 mmHg | Standard Error 1.52 |
p-value: 0.427ANCOVA
Secondary
Change in Mean 24 Hour Systolic Blood Pressure From Baseline to Endpoint
Change from baseline to endpoint in average systolic blood pressure measured over 24 hours by an ambulatory blood pressure monitor
Time frame: 12 weeks
Population: Intent to treat; Last observation carried forward
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide BID | Change in Mean 24 Hour Systolic Blood Pressure From Baseline to Endpoint | Baseline (Week 0) | 126.61 mmHg | Standard Error 3.04 |
| Exenatide BID | Change in Mean 24 Hour Systolic Blood Pressure From Baseline to Endpoint | Change at endpoint (Week 12) | -0.81 mmHg | Standard Error 2.67 |
| Placebo | Change in Mean 24 Hour Systolic Blood Pressure From Baseline to Endpoint | Baseline (Week 0) | 119.93 mmHg | Standard Error 3.1 |
| Placebo | Change in Mean 24 Hour Systolic Blood Pressure From Baseline to Endpoint | Change at endpoint (Week 12) | -0.34 mmHg | Standard Error 2.72 |
p-value: 0.9034ANCOVA
Secondary
Change in Nighttime (2400-0600) Heart Rate From Baseline to Endpoint
Change from baseline to endpoint in nighttime (2400-0600) heart rate as measured by an ambulatory blood pressure monitor
Time frame: 12 weeks
Population: Intent to treat; Last observation carried forward
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide BID | Change in Nighttime (2400-0600) Heart Rate From Baseline to Endpoint | Baseline (Week 0) | 71.54 beats per minute | Standard Error 2.12 |
| Exenatide BID | Change in Nighttime (2400-0600) Heart Rate From Baseline to Endpoint | Change at endpoint (Week 12) | 1.43 beats per minute | Standard Error 1.79 |
| Placebo | Change in Nighttime (2400-0600) Heart Rate From Baseline to Endpoint | Baseline (Week 0) | 71.77 beats per minute | Standard Error 2.16 |
| Placebo | Change in Nighttime (2400-0600) Heart Rate From Baseline to Endpoint | Change at endpoint (Week 12) | -0.28 beats per minute | Standard Error 1.83 |
p-value: 0.5077ANCOVA