Pharmacokinetics of Capmatinib in Participants with Hepatic Impairment: A Phase 1, Open-label, Single-dose, Parallel-group Study

Overview

Journal Br J Clin Pharmacol

Specialty Pharmacology

Date 2021 May 28

PMID 34046915

Citations 2

Authors

Xinhui Chen

Xiaoming Cui

Nathalie Pognan

Michelle Quinlan

Shruti Kapoor

Gholamreza Rahmanzadeh

Monica Giovannini

Thomas C Marbury

Affiliations

Soon will be listed here.

Abstract

Aims: Capmatinib, a mesenchymal-epithelial transition factor tyrosine kinase inhibitor, is metabolized by cytochrome P450 (CYP) 3A4 and aldehyde oxidase. In individuals with hepatic impairment, alterations in hepatobiliary excretion and metabolism could lead to higher capmatinib exposure. We compared the pharmacokinetics of a single oral dose of capmatinib 200 mg administered to participants with varying degrees of hepatic impairment vs. matched controls with normal hepatic function.

Methods: This phase 1, multicentre, open-label, parallel-group study enrolled adult participants with normal hepatic function and mild, moderate and severe hepatic impairments. Eligible participants received a single oral dose of 200 mg capmatinib. The pharmacokinetic parameters of capmatinib were analysed and compared across participants with impaired and normal hepatic function.

Results: Of 31 enrolled participants, 29 had an evaluable pharmacokinetic profile: normal (n = 9); mild (n = 6); moderate (n = 8); severe (n = 6). Compared with the normal group, geometric mean (GM) maximum (peak) observed plasma drug concentration after single-dose administration decreased by 27.6% in the mild group (GM ratio [GMR] = 0.724; 90% confidence interval [CI]: 0.476-1.10), by 17.2% in the moderate group (GMR = 0.828; 90% CI: 0.563-1.22) and remained unchanged in the severe group (GMR = 1.02; 90% CI: 0.669-1.55). Compared with the normal group, GM area under the plasma concentration-time curve from time zero to infinity decreased by 23.3% in the mild group (GMR = 0.767; 90% CI: 0.532-1.11), by 8.6% in the moderate group (GMR = 0.914; 90% CI: 0.652-1.28) and increased by 24% in the severe group (GMR = 1.24; 90% CI: 0.858-1.78).

Conclusion: Mild, moderate and severe hepatic impairment did not have a clinically relevant impact on capmatinib pharmacokinetics. No new safety findings are reported in this study.

Citing Articles

HPLC with Fluorescence and Photodiode Array Detection for Quantifying Capmatinib in Biological Samples: Application to In Vivo and In Vitro Studies.

Zayed A, Jaber S, Al Hroot J, Hawamdeh S, Ayoub N, Qinna N Molecules. 2022; 27(23).

PMID: 36500674 PMC: 9738601. DOI: 10.3390/molecules27238582.

Pharmacokinetics of capmatinib in participants with hepatic impairment: A phase 1, open-label, single-dose, parallel-group study.

Chen X, Cui X, Pognan N, Quinlan M, Kapoor S, Rahmanzadeh G Br J Clin Pharmacol. 2021; 88(1):91-102.

PMID: 34046915 PMC: 9291822. DOI: 10.1111/bcp.14929.

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