Oral Administration of Peptides; Absorption From Gastrointestinal Tract

Study Overview
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Brief Summary
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Context: Oral formulations of GLP-1 and PYY3-36, two satiety peptides, were studied. An oral delivery system would be preferable in many of the possible therapeutic indications of these peptides. Objectives: Our objective was to establish the pharmacological profile of increasing oral doses of GLP-1 and PYY3-36 in healthy volunteers. In addition, the pharmacological effects of GLP-1 were investigated. Setting: Single center escalating dose study with oral applications. Subjects and Methods: In the first part, GLP-1 was given orally to 6 male subjects; the treatment consisted of one of the following oral doses of either GLP-1 (0.5, 1.0, 2.0 and 4.0 mg) or placebo. In the second part, PYY3-36 was given orally to another 6 healthy male subjects; the treatment consisted of one of the following oral doses of either PYY3-36 (0.25, 0.5, 1.0, 2.0 and 4.0 mg) or placebo.

Detailed Description
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The study was conducted as a phase I, open, placebo-controlled, dose-escalating study. In part I, six treatments, separated by at least 7 days, were performed in 6 male subjects; treatments consisted of one oral dose of GLP-1(7-36 amide) (0.5, 1.0, 2.0, and 4 mg) or placebo; the last treatment was an intravenous infusion of GLP-1 given for 45 min (0.4 pmol/kg per min infused for 45 min). The treatments were identical in design except for the oral dose of GLP-1. In part II, six oral treatments, separated by at least 7 days, were given in an additional 6 male subjects; treatments consisted of one oral dose of PYY3-36 (0.25, 0.5, 1.0, 2.0, and 4 mg) or placebo; an intravenous infusion of PYY3-36 could not be given as no GMP conform PYY3-36 was available for use in humans. Blood was drawn in regular intervals in EDTA tubes containing aprotinin (500 kIU/ml blood) and a DPP-IV inhibitor for hormone determinations: -30, -15, 0, 15, 30, 45, 60, 75, 90, 120, 150, 180, 240, 300 min.

Official Title
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Pharmacokinetics and Pharmacodynamic Effects of Oral GLP-1 and PYY3-36: a Proof of Concept Study in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Increasing doses of GLP-1
* Drug: PYY3-36


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy males Exclusion Criteria: females

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Increasing doses of GLP-1|nan|
|Drug: PYY3-36|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentrations of GLP-1 and PYY3-36 |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect on ghrelin secretion |  |  | 
| Effect on insulin (GLP-1 only) |  |  | 
| Adverse events |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kinetics of GLP-1 and PYY3-36; increasing oral doses