Oral Administration of Peptides; Absorption From Gastrointestinal Tract

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00468884
• Other study ID #: Oral GLP-1 and PYY
• Status: Completed
• Phase: Phase 1
• First received: May 2, 2007
• Last updated: October 16, 2008
• Start date: October 2006
• Est. completion date: February 2007

Study information

• Verified date: October 2008
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Ethikkommission
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: February 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• healthy males

Exclusion Criteria:

• females

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Increasing doses of GLP-1

• PYY3-36

Locations

Country	Name	City	State
Switzerland	Clinical Research Centre, University Hospital	Basel

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland

Country where clinical trial is conducted

Switzerland, 

References & Publications (1)

Degen L, Oesch S, Casanova M, Graf S, Ketterer S, Drewe J, Beglinger C. Effect of peptide YY3-36 on food intake in humans. Gastroenterology. 2005 Nov;129(5):1430-6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma concentrations of GLP-1 and PYY3-36
Secondary	Effect on ghrelin secretion
Secondary	Effect on insulin (GLP-1 only)
Secondary	Adverse events