A Study to Assess the Effects of Exenatide on Insulin Secretion Rates Using a Graded Infusion of Intravenous Glucose (0000-099)(COMPLETED)

Study Overview
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Brief Summary
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A four-period study to evaluate if the grade glucose infusion procedure will be able to detect an increase in beta-cell glucose sensitivity from exenatide compared to no treatment in healthy subjects.

Official Title
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A Randomized, 4-Period Study to Assess the Effects of Exenatide on Insulin Secretion Rates Using a Graded Infusion of Intravenous Glucose

Conditions
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Healthy

Intervention / Treatment
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* Other: Comparator: Treatment A
* Drug: Comparator: Treatment B
* Drug: Comparator: Treatment C
* Procedure: Comparator: graded glucose infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is in good health Subject is a non-smoker Exclusion Criteria: Subject has irritable bowel disease Subject has a history of cancer Subject has a history of hypertension requiring treatment Subject is unable to refrain from the use of any prescription or non-prescription medication Subject consumes excessive amounts of alcohol or caffeine Subject has had major surgery, donated blood or participated in another investigational study in the past 4 weeks

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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Sequence 1<br>A-B-C-C | Other: Comparator: Treatment A<br>* No Treatment<br>Drug: Comparator: Treatment B<br>* single dose administration of exenatide 5ug by subcutaneous injection<br>Drug: Comparator: Treatment C<br>* single dose administration of exenatide 10ug by subcutaneous injection<br>Procedure: Comparator: graded glucose infusion<br>* A stepwise graded infusion of glucose (20% dextrose [D20]) with a stable rate of infusion maintained for 40 minutes for each of 5 steps, with steps at 2,4,6,8 and 12 mg/kg/min. Infusion will be performed during each of the 4 treatment periods.<br>|
| Experimental: Treatment Sequence 2<br>B-C-A-C | Other: Comparator: Treatment A<br>* No Treatment<br>Drug: Comparator: Treatment B<br>* single dose administration of exenatide 5ug by subcutaneous injection<br>Drug: Comparator: Treatment C<br>* single dose administration of exenatide 10ug by subcutaneous injection<br>Procedure: Comparator: graded glucose infusion<br>* A stepwise graded infusion of glucose (20% dextrose [D20]) with a stable rate of infusion maintained for 40 minutes for each of 5 steps, with steps at 2,4,6,8 and 12 mg/kg/min. Infusion will be performed during each of the 4 treatment periods.<br>|
| Experimental: Treatment Sequence 3<br>C-A-B-C | Other: Comparator: Treatment A<br>* No Treatment<br>Drug: Comparator: Treatment B<br>* single dose administration of exenatide 5ug by subcutaneous injection<br>Drug: Comparator: Treatment C<br>* single dose administration of exenatide 10ug by subcutaneous injection<br>Procedure: Comparator: graded glucose infusion<br>* A stepwise graded infusion of glucose (20% dextrose [D20]) with a stable rate of infusion maintained for 40 minutes for each of 5 steps, with steps at 2,4,6,8 and 12 mg/kg/min. Infusion will be performed during each of the 4 treatment periods.<br>|
| Experimental: Treatment Sequence 4<br>A-C-B-C | Other: Comparator: Treatment A<br>* No Treatment<br>Drug: Comparator: Treatment B<br>* single dose administration of exenatide 5ug by subcutaneous injection<br>Drug: Comparator: Treatment C<br>* single dose administration of exenatide 10ug by subcutaneous injection<br>Procedure: Comparator: graded glucose infusion<br>* A stepwise graded infusion of glucose (20% dextrose [D20]) with a stable rate of infusion maintained for 40 minutes for each of 5 steps, with steps at 2,4,6,8 and 12 mg/kg/min. Infusion will be performed during each of the 4 treatment periods.<br>|
| Experimental: Treatment Sequence 5<br>B-A-C-C | Other: Comparator: Treatment A<br>* No Treatment<br>Drug: Comparator: Treatment B<br>* single dose administration of exenatide 5ug by subcutaneous injection<br>Drug: Comparator: Treatment C<br>* single dose administration of exenatide 10ug by subcutaneous injection<br>Procedure: Comparator: graded glucose infusion<br>* A stepwise graded infusion of glucose (20% dextrose [D20]) with a stable rate of infusion maintained for 40 minutes for each of 5 steps, with steps at 2,4,6,8 and 12 mg/kg/min. Infusion will be performed during each of the 4 treatment periods.<br>|
| Experimental: Treatment Sequence 6<br>C-B-A-C | Other: Comparator: Treatment A<br>* No Treatment<br>Drug: Comparator: Treatment B<br>* single dose administration of exenatide 5ug by subcutaneous injection<br>Drug: Comparator: Treatment C<br>* single dose administration of exenatide 10ug by subcutaneous injection<br>Procedure: Comparator: graded glucose infusion<br>* A stepwise graded infusion of glucose (20% dextrose [D20]) with a stable rate of infusion maintained for 40 minutes for each of 5 steps, with steps at 2,4,6,8 and 12 mg/kg/min. Infusion will be performed during each of the 4 treatment periods.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| beta-cell glucose sensitivity (slope of the relationship between insulin secretion rate and glucose) |  | 0-160 minutes after start of infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety and tolerability of a graded glucose infusion procedure measured by the number of clinical adverse experiences |  | 11 weeks |