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Open Access 01-10-2020 | Pharmacokinetics | PHASE I STUDIES

Open-label, single-center, phase I trial to investigate the mass balance and absolute bioavailability of the highly selective oral MET inhibitor tepotinib in healthy volunteers

Authors: Andreas Johne, Holger Scheible, Andreas Becker, Jan Jaap van Lier, Peter Wolna, Michael Meyring

Published in: Investigational New Drugs | Issue 5/2020

Summary

Tepotinib (MSC2156119J) is an oral, potent, highly selective MET inhibitor. This open-label, phase I study in healthy volunteers (EudraCT 2013-003226-86) investigated its mass balance (part A) and absolute bioavailability (part B). In part A, six participants received tepotinib orally (498 mg spiked with 2.67 MBq [¹⁴C]-tepotinib). Blood, plasma, urine, and feces were collected up to day 25 or until excretion of radioactivity was <1% of the administered dose. In part B, six participants received 500 mg tepotinib orally as a film-coated tablet, followed by an intravenous [¹⁴C]-tepotinib tracer dose (53–54 kBq) 4 h later. Blood samples were collected until day 14. In part A, a median of 92.5% (range, 87.1–96.9%) of the [¹⁴C]-tepotinib dose was recovered in excreta. Radioactivity was mainly excreted via feces (median, 78.7%; range, 69.4–82.5%). Urinary excretion was a minor route of elimination (median, 14.4% [8.8–17.7%]). Parent compound was the main constituent in excreta (45% [feces] and 7% [urine] of the radioactive dose). M506 was the only major metabolite. In part B, absolute bioavailability was 72% (range, 62–81%) after oral administration of 500 mg tablets (the dose and formulation used in phase II trials). In conclusion, tepotinib and its metabolites are mainly excreted via feces; parent drug is the major eliminated constituent. Oral bioavailability of tepotinib is high, supporting the use of the current tablet formulation in clinical trials. Tepotinib was well tolerated in this study with healthy volunteers.

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Title: Open-label, single-center, phase I trial to investigate the mass balance and absolute bioavailability of the highly selective oral MET inhibitor tepotinib in healthy volunteers
Authors: Andreas Johne
Holger Scheible
Andreas Becker
Jan Jaap van Lier
Peter Wolna
Michael Meyring
Publication date: 01-10-2020
Publisher: Springer US
Keyword: Pharmacokinetics
Published in: Investigational New Drugs / Issue 5/2020
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-020-00926-1

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