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At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
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Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 6/2019

Open Access 01-06-2019 | Original Research Article

Safety and Pharmacokinetics of Single and Multiple Ascending Doses of the Novel Oral Human GLP-1 Analogue, Oral Semaglutide, in Healthy Subjects and Subjects with Type 2 Diabetes

Authors: Charlotte Granhall, Morten Donsmark, Thalia M. Blicher, Georg Golor, Flemming L. Søndergaard, Mette Thomsen, Tine A. Bækdal

Published in: Clinical Pharmacokinetics | Issue 6/2019

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Abstract

Background

Oral semaglutide is a novel tablet containing the human glucagon-like peptide-1 (GLP‑1) analogue semaglutide, co-formulated with the absorption enhancer sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC). The safety and pharmacokinetics of oral semaglutide were investigated in two randomised, double-blind, placebo-controlled trials.

Methods

In a single-dose, first-in-human trial, 135 healthy males received oral semaglutide (2–20 mg semaglutide co-formulated with 150–600 mg SNAC) or placebo with SNAC. In a 10-week, once-daily, multiple-dose trial, 84 healthy males received 20 or 40 mg oral semaglutide (with 300 mg SNAC), placebo, or placebo with SNAC, and 23 males with type 2 diabetes (T2D) received 40 mg oral semaglutide (with 300 mg SNAC), placebo, or placebo with SNAC.

Results

Oral semaglutide was safe and well-tolerated in both trials. The majority of adverse events (AEs) were mild, with the most common AEs being gastrointestinal disorders. In the single-dose trial, semaglutide exposure was highest when co-formulated with 300 mg SNAC. In the multiple-dose trial, semaglutide exposure was approximately twofold higher with 40 versus 20 mg oral semaglutide in healthy males, in accordance with dose proportionality, and was similar between healthy males and males with T2D. The half-life of semaglutide was approximately 1 week in all groups.

Conclusion

The safety profile of oral semaglutide was as expected for the GLP-1 receptor agonist drug class. Oral semaglutide co-formulated with 300 mg SNAC was chosen for further clinical development. The pharmacokinetic results supported that oral semaglutide is suitable for once-daily dosing.

ClinicalTrials.gov identifiers

NCT01037582, NCT01686945.
Appendix
Available only for authorised users
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Metadata
Title
Safety and Pharmacokinetics of Single and Multiple Ascending Doses of the Novel Oral Human GLP-1 Analogue, Oral Semaglutide, in Healthy Subjects and Subjects with Type 2 Diabetes
Authors
Charlotte Granhall
Morten Donsmark
Thalia M. Blicher
Georg Golor
Flemming L. Søndergaard
Mette Thomsen
Tine A. Bækdal
Publication date
01-06-2019
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 6/2019
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.1007/s40262-018-0728-4

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