Oral Administration of Peptides; Absorption From Gastrointestinal Tract
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.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Pharmacokinetics and Pharmacodynamic Effects of Oral GLP-1 and PYY3-36: a Proof of Concept Study in Healthy Subjects|
- Plasma concentrations of GLP-1 and PYY3-36
- Effect on ghrelin secretion
- Effect on insulin (GLP-1 only)
- Adverse events
|Study Start Date:||October 2006|
|Study Completion Date:||February 2007|
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00468884
|Clinical Research Centre, University Hospital|
|Basel, Switzerland, CH-4031|
|Principal Investigator:||Christoph Beglinger, MD||University Hospital, 4031 Basel, Switzerland|