A Study to Compare Methodologies for Assessing Glucose-Dependent Insulin Secretion (0000-104)(COMPLETED)

Study Overview
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Brief Summary
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This study will compare graded glucose infusion (GGI) to the hyperglycemic clamp (HGC) for assessment of glucose-dependent insulin secretion (GDIS) using exenatide as a probe.

Official Title
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A Randomized Clinical Trial to Study Glucose Dependent Insulin Secretion Methodologies in Healthy Lean Male Subjects

Conditions
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The Methodology Assessment of Glucose Dependent Insulin Secretion

Intervention / Treatment
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* Drug: Comparator: exenatide
* Drug: Comparator: exenatide
* Drug: Comparator: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has a Body Mass Index (BMI) of less than or equal to 26 kg/m2 at screening Subject is judged to be in good health Subject has been a nonsmoker for at least 3 months Subject is willing to avoid strenuous physical activity for the duration of the study Exclusion Criteria: Subject has a history of high blood pressure requiring treatment Subject has a history of diabetes or a family history of diabetes mellitus Subject is unable to discontinue all prescription and non-prescription drugs for duration of study Subject consumes more than 3 alcoholic beverages per day Subject consumes more than 6 servings of caffeinated beverages per day (1 serving = 120mg caffeine) Subject has had major surgery or has donated or loss 1 unit of blood within 4 weeks of screening Subject has multiple and/or severe allergies to foods or drugs Subject is a regular user of illegal drugs Subject is unwilling or unable to consume the standardized meals during the study and/or is on a carbohydrate restricted diet

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>exenatide 5mcg | Drug: Comparator: exenatide<br>* exenatide in two 5mcg subcutaneous doses 120 minutes apart, followed by either HGC or GGI. After a 14 day washout period two additional 5mcg doses will be administered, followed by HCG or GGI.<br>* Other names: Byetta;|
| Active Comparator: 2<br>exenatide 1.5mcg | Drug: Comparator: exenatide<br>* exenatide in two 1.5mcg subcutaneous doses 120 minutes apart, followed by either HGC or GGI. After a 14 day washout period two additional 1.5mcg doses will be administered, followed by HCG or GGI.<br>* Other names: Byetta;|
| Placebo Comparator: 3<br>Placebo | Drug: Comparator: Placebo<br>* 5% osmitrol in two 60 mcL subcutaneous doses 120 minutes apart, followed by either HGC or GGI. After a 14 day washout period two additional 60 mcL doses will be administered, followed by HCG or GGI.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Insulin Secretion Rate (ISR) Normalized to Ambient Plasma Glucose | Comparison of Glucose Dependent Insulin Secretion (GDIS) measured after HGC at steady-state to GDIS measured after GGI at the highest glucose infusion rate. Insulin Secretion Rate (ISR)/ Blood Glucose (BG) | Steady-state of HGC: 90 - 120 minutes post dose; highest glucose infusion rate of GGI: 120 - 160 minutes post dose | 
| Change From Baseline in C-peptide Concentration |  | Pre and Post glucose infusion | 
| Change From Baseline in Insulin Concentration |  | Pre and Post glucose infusion |