Clinical trial NCT00894322: A Study to Examine the Pharmacokinetics, Tolerability, Safety and Efficacy of Exenatide Once Weekly Suspension
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Type 2 Diabetes Mellitus
Keywords: diabetes
exenatide once weekly
Byetta
Amylin
Lilly
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Eli Lilly and Company
First posted: 2009-05-07
Enrollment: 65
Sex: ALL
Minimum age (years): 19
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Area Under the Curve (AUC) for Single Dose of 10 mg Exenatide (Cohort 1) in Healthy Participants in the Pharmacokinetic Evaluable Population
timeFrame: Day 1, Week 12
measure: Maximum Concentration (Cmax) for Single Dose of 10 mg Exenatide (Cohort 1) in Healthy Participants in the Pharmacokinetic Evaluable Population
timeFrame: Day 1, Week 12
measure: Time to Maximum Concentration (Tmax) for Single Dose of 10 mg Exenatide (Cohort 1) in Healthy Participants in the Pharmacokinetic Evaluable Population
timeFrame: Day 1, Week 12
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Injection Site TEAEs, Serious Adverse Events (SAEs), Deaths, and Withdrawals Due to AEs in Cohort 1 and Cohort 2 in Intent to Treat (ITT) Population
timeFrame: Day 1 to Week12
measure: Number of Participants With Concomitant Medications in Cohort 1 and Cohort 2 in ITT Population
timeFrame: Day 1 to 12 weeks
measure: Mean Change From Baseline to End of Study in Sitting Diastolic and Systolic Blood Pressure in Cohorts 1 and 2 in ITT Population
timeFrame: Day 1 to Week 12
measure: Mean Change From Baseline to End of Study in Sitting Heart Rate in Cohorts 1 and 2 in ITT Population
timeFrame: Day 1 to Week 12
measure: Number of Participants With Hematology and Serum Chemistry Laboratory Values of Potential Clinical Importance in Cohorts 1 and 2 in ITT Population
timeFrame: Day 1 to Week 12
measure: Antibody Titers for Participants With Treatment Emergent Positive Antibodies to Exenatide in Participants Who Received Exenatide in Cohorts 1 and 2
timeFrame: Day 1 to Week 12
measure: Area Under the Curve (AUC) for 2 mg Exenatide (Cohort 2) in Participants With Diabetes in the Pharmacokinetic Evaluable Population
timeFrame: Week 10-11; Weeks 10 - 12
measure: Average Exenatide Concentration (Cave) of 2 mg Exenatide (Cohort 2) in Participants With Diabetes in the Pharmacokinetic Evaluable Population
timeFrame: Week 10 - Week 11; Week 10 - Week 12
measure: Maximum Concentration (Cmax) for 2 mg Exenatide (Cohort 2) in Participants With Diabetes in the Pharmacokinetic Evaluable Population
timeFrame: Week 10, Weeks 10-11, Weeks 10-12
measure: Time to Maximum Concentration (Tmax) of 2 mg Exenatide (Cohort 2) in Participants With Diabetes in Pharmacokinetic Evaluable Population
timeFrame: Week 10, Weeks 10-11, Weeks 10-12
Secondary outcomes:
measure: AUC (0 Hour to 168 Hour) for 10 mg Exenatide (Cohort 1) in Healthy Participants in the Pharmacokinetic Evaluable Population
timeFrame: Day 1 to Week 1
measure: Average Exenatide Concentration (Cave) of 10 mg Exenatide (Cohort 1) in Healthy Participants in the Pharmacokinetic Evaluable Population
timeFrame: Day 1 to Week 1
measure: Least Square Mean Change From Baseline in Hemoglobin A1c (HbA1c) to Week 12 in Participants With Diabetes (Cohort 2) in the ITT Population
timeFrame: Day 1 to Week 12
measure: Number of Participants Achieving HbA1c Less Than Equal to (<=) 6.5% and Less Than (<) 7% at Week 12 in Participants With Diabetes (Cohort 2) in the ITT Population
timeFrame: Week 12
measure: Mean Change From Baseline at Week 12 in Body Weight in Participants With Diabetes (Cohort 2) in the ITT Population
timeFrame: Baseline, Week 12
measure: Mean Change From Baseline at Week 12 in Fasting Plasma Glucose in Participants With Diabetes (Cohort 2) for the ITT Population
timeFrame: Baseline, Week 12
Other outcomes:
Locations:
city: Lincoln
country: United States
facility: Research Site
state: Nebraska
Study officials:
affiliation: Amylin Pharmaceuticals, LLC.
name: Vice President, Clinical Development
role: STUDY_DIRECTOR
References: