Phase 2
Completed N=65
A Study to Examine the Pharmacokinetics, Tolerability, Safety and Efficacy of Exenatide Once Weekly Suspension
Source: ClinicalTrials.gov NCT00894322 ↗Enrolled (actual)
65
Serious AEs
1.5%
Results posted
May 2014
Primary outcomePrimary: Area Under the Curve (AUC) for Single Dose of 10 mg Exenatide (Cohort 1) in Healthy Participants in the Pharmacokinetic Evaluable Population — 125.6; 147220.2 pg*h/mL
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Curve (AUC) for Single Dose of 10 mg Exenatide (Cohort 1) in Healthy Participants in the Pharmacokinetic Evaluable Population |
125.6; 147220.2 | — |
| PRIMARY Maximum Concentration (Cmax) for Single Dose of 10 mg Exenatide (Cohort 1) in Healthy Participants in the Pharmacokinetic Evaluable Population |
34.9; 331.2 | — |
| PRIMARY Time to Maximum Concentration (Tmax) for Single Dose of 10 mg Exenatide (Cohort 1) in Healthy Participants in the Pharmacokinetic Evaluable Population |
7.0; 998.1 | — |
| PRIMARY 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 |
26; 22; 9; 16; 18; 7 | — |
| PRIMARY Number of Participants With Concomitant Medications in Cohort 1 and Cohort 2 in ITT Population |
30; 21; 11 | — |
| PRIMARY Mean Change From Baseline to End of Study in Sitting Diastolic and Systolic Blood Pressure in Cohorts 1 and 2 in ITT Population |
6.2; 4.6; 6.8; -1.4; -8.4; -1.7 | — |
| PRIMARY Mean Change From Baseline to End of Study in Sitting Heart Rate in Cohorts 1 and 2 in ITT Population |
-7.5; -5.4; -9.1 | — |
| PRIMARY Number of Participants With Hematology and Serum Chemistry Laboratory Values of Potential Clinical Importance in Cohorts 1 and 2 in ITT Population |
0; 0; 1; 0; 1; 0 | — |
| PRIMARY Antibody Titers for Participants With Treatment Emergent Positive Antibodies to Exenatide in Participants Who Received Exenatide in Cohorts 1 and 2 |
25.0; 25.0; 394.6; 202.6; NA; 295.9 | — |
| PRIMARY Area Under the Curve (AUC) for 2 mg Exenatide (Cohort 2) in Participants With Diabetes in the Pharmacokinetic Evaluable Population |
1535.3; 49100.2; 101615.0 | — |
| PRIMARY Average Exenatide Concentration (Cave) of 2 mg Exenatide (Cohort 2) in Participants With Diabetes in the Pharmacokinetic Evaluable Population |
292.7; 302.4 | — |
| PRIMARY Maximum Concentration (Cmax) for 2 mg Exenatide (Cohort 2) in Participants With Diabetes in the Pharmacokinetic Evaluable Population |
304.9; 362.6; 410.5 | — |
| PRIMARY Time to Maximum Concentration (Tmax) of 2 mg Exenatide (Cohort 2) in Participants With Diabetes in Pharmacokinetic Evaluable Population |
1.4; 34.3; 60.0 | — |
| SECONDARY AUC (0 Hour to 168 Hour) for 10 mg Exenatide (Cohort 1) in Healthy Participants in the Pharmacokinetic Evaluable Population |
3269.6 | — |
| SECONDARY Average Exenatide Concentration (Cave) of 10 mg Exenatide (Cohort 1) in Healthy Participants in the Pharmacokinetic Evaluable Population |
32.5 | — |
| SECONDARY Least Square Mean Change From Baseline in Hemoglobin A1c (HbA1c) to Week 12 in Participants With Diabetes (Cohort 2) in the ITT Population |
-0.87; 0.08 | 0.0013 sig |
| SECONDARY 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 |
22; 12; 9; 1; 14; 2 | 0.0033 sig |
| SECONDARY Mean Change From Baseline at Week 12 in Body Weight in Participants With Diabetes (Cohort 2) in the ITT Population |
-1.41; -0.39 | 0.2285 |
| SECONDARY Mean Change From Baseline at Week 12 in Fasting Plasma Glucose in Participants With Diabetes (Cohort 2) for the ITT Population |
-32; 8 | 0.0035 sig |
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
Data sourced from ClinicalTrials.gov (NCT00894322). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.