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

Phase 3

Completed

Conditions: Type 2 Diabetes Mellitus

Interventions: Drug: exenatide twice daily
Drug: exenatide once weekly

Registration Number: NCT00877890

Lead Sponsor: AstraZeneca

Brief Summary: This study will compare the effects of commercially manufactured exenatide once weekly and exenatide BID in subjects whose type 2 diabetes is managed with diet and exercise alone or with oral antidiabetic medications. The study will examine glycemic control (as measured by HbA1C), safety, and tolerability.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 254

Inclusion Criteria

Has been diagnosed with type 2 diabetes mellitus
Has hemoglobin-specific A1c fraction (HbA1c) of 7.1% to 11.0%, inclusive, at screening
Has a body mass index (BMI) of 25 kg/m2 to 45 kg/m2, inclusive, at screening
Has been treated with diet and exercise alone or in combination with a stable regimen of metformin (MET), a sulfonylurea (SU), a thiazolidinedione (TZD), a combination of metformin and an SU, a combination of metformin and a TZD, or a combination of an SU and a TZD for a minimum of 2 months prior to screening
Either is not treated with or has been on a stable treatment regimen with any of the following medications for a minimum of 2 months prior to screening:
- Hormone replacement therapy (female subjects)
- Oral contraceptives (female subjects)
- Antihypertensive agents
- Lipid-lowering agents
- Thyroid replacement therapy
- Antidepressant agents
- Drugs known to affect body weight, including prescription medications (e.g. orlistat [XENICAL®], sibutramine [MERIDIA®], topiramate [TOPAMAX®]) and over the counter antiobesity agents

Exclusion Criteria

Has ever been exposed to exenatide (exenatide once weekly [exenatide LAR], exenatide BID, BYETTA, or any other formulation) or any glucagon-like peptide-1 (GLP-1) analog
Has received any investigational drug within one month (or five half-lives of the investigational drug, whichever is greater) of screening
Has been treated, is currently being treated, or is expected to require or undergo treatment with any of the following treatment excluded medications:
- Any dipeptidyl peptidase 4 (DPP-4) inhibitor within 3 months prior to screening
- Alpha glucosidase inhibitor, meglitinide, nateglinide, or pramlintide (SYMLIN®) within 30 days of screening
- Insulin within 2 weeks of screening or for more than 1 week within 3 months of screening
- Systemic corticosteroids by oral, intravenous, or intramuscular route; or potent, inhaled, or intrapulmonary (including ADVAIR®) steroids known to have a high rate of systemic absorption

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	exenatide twice daily	-
1	exenatide once weekly	-

Primary Outcome Measures

Name	Time	Method
Change in HbA1c From Baseline to Week 24	Day 1, Week 24	Change in HbA1c from baseline (Day 1) to Week 24 \[Week 24 - Baseline\].

Secondary Outcome Measures

Name	Time	Method
Percentage of Subjects Achieving HbA1c Target of <7%	Week 24	Percentages of subjects achieving HbA1c target value of \<7% at Week 24.
Change in Total Cholesterol From Baseline to Week 24	Day 1, Week 24	Change in total cholesterol from baseline (Day 1) to Week 24.
Ratio of Triglycerides at Week 24 to Baseline	Day 1, Week 24	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.
Change in Fasting Plasma Glucose From Baseline to Week 24	Day 1, Week 24	Change in fasting plasma glucose from baseline (Day 1) to Week 24.
Percentage of Subjects Achieving Fasting Plasma Glucose Target of <=126 mg/dL	Week 24	Percentages of subjects achieving fasting plasma glucose target of \<=126 mg/dL at Week 24.
Change in Body Weight From Baseline to Week 24	Day 1, Week 24	Change in body weight from baseline (Day 1) to Week 24.
Change in Sitting Diastolic Blood Pressure From Baseline to Week 24	Day 1, Week 24	Change in diastolic blood pressure from baseline (Day 1) to Week 24.
Change in High-density Lipoprotein (HDL) From Baseline to Week 24	Day 1, Week 24	Change in HDL from baseline (Day 1) to Week 24.
Assessment on Event Rate of Treatment-emergent Major Hypoglycemic Events	Day 1 to Week 24	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.
Percentage of Subjects Achieving HbA1c Target of <=6.5%	Week 24	Percentages of subjects achieving HbA1c target values of \<=6.5% at Week 24.
Change in Sitting Systolic Blood Pressure From Baseline to Week 24	Day 1, Week 24	Change in systolic blood pressure from baseline (Day 1) to Week 24.
Assessment on Event Rate of Treatment-emergent Minor Hypoglycemic Events	Day 1 to Week 24	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.