A Study to Examine the Pharmacokinetics, Tolerability, Safety and Efficacy of Exenatide Once Weekly Suspension

A Two-Cohort, Single- and Repeat Dose Study to Examine the Pharmacokinetics, Tolerability, and Safety of Ready to Use Exenatide Once Weekly in Healthy Subjects and in Subjects With Type 2 Diabetes Mellitus

This study is designed to evaluate the pharmacokinetics, tolerability, and safety of exenatide once weekly suspension in both healthy subjects and in subjects with type 2 diabetes. The study will also evaluate efficacy in the type 2 diabetes patients. Development of this exenatide once weekly presentation would eliminate the need to reconstitute the product prior to use.

Inclusion Criteria:

Cohort 1:

• Is 19 to 65 years old
• Has a body mass index (BMI) of 23 kg/m2 to 35 kg/m2, inclusive, at study start

Cohort 2:

• Is 19 to 75 years old

• Has been diagnosed with type 2 diabetes mellitus

• Has HbA1c of 7.1% to 10.0%, inclusive, at study start

• Has a body mass index (BMI) of 25 kg/m2 to 45 kg/m2, inclusive, at study start

• Has been treated with diet and exercise alone or with a stable regimen of metformin, a TZD, or a combination of metformin and a TZD, for a minimum of 2 months prior to study start

• 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 study start:

  • Hormone replacement therapy (female subjects)
  • Oral contraceptives (female subjects)
  • Antihypertensive agents
  • Lipid-lowering agents
  • Thyroid replacement therapy
  • Antidepressant agents

Exclusion Criteria:

Cohort 1:

• Has a personal history of diabetes mellitus (including impaired glucose tolerance, impaired fasting glucose, or gestational diabetes)
• Has received any investigational drug within 30 days (or 5 half-lives of the investigational drug, whichever is greater) prior to study start
• Has ever been exposed to exenatide (BYETTA, exenatide once weekly, or any other formulation of exenatide) or any GLP 1 analog

Cohort 2:

• Has received any investigational drug within 30 days (or 5 half-lives of the investigational drug, whichever is greater) prior to study start

• Has ever been exposed to exenatide (BYETTA, exenatide once weekly, or any other formulation of exenatide) or any GLP 1 analog

• Has been treated, is currently being treated, or is expected to require or undergo treatment with any of the following treatment-excluded medications:

  • Any DPP-4 inhibitor or sulfonylurea (SU) within 3 months prior to study start
  • Alpha glucosidase inhibitor, meglitinide, nateglinide, or pramlintide (SYMLIN®) within 30 days prior to study start
  • Insulin within 2 weeks prior to study start or for more than 1 week within 3 months prior to study start
  • 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
  • Prescription or over-the-counter weight loss medications within 3 months prior to study start