Skip to main content
main-content

27.03.2020 | PHASE I STUDIES | Ausgabe 5/2020 Open Access

Investigational New Drugs 5/2020

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

Zeitschrift:
Investigational New Drugs > Ausgabe 5/2020
Autoren:
Andreas Johne, Holger Scheible, Andreas Becker, Jan Jaap van Lier, Peter Wolna, Michael Meyring
Wichtige Hinweise

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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.

Unsere Produktempfehlungen

e.Med Interdisziplinär

Kombi-Abonnement

Für Ihren Erfolg in Klinik und Praxis - Die beste Hilfe in Ihrem Arbeitsalltag als Mediziner

Mit e.Med Interdisziplinär erhalten Sie Zugang zu allen CME-Fortbildungen und Fachzeitschriften auf SpringerMedizin.de.

Literatur
Über diesen Artikel

Weitere Artikel der Ausgabe 5/2020

Investigational New Drugs 5/2020 Zur Ausgabe

Neu im Fachgebiet Onkologie

Mail Icon II Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update Onkologie und bleiben Sie gut informiert – ganz bequem per eMail.

Bildnachweise