P2X3 Receptor Antagonist Eliapixant in Phase I Clinical Trials: Safety and Inter-ethnic Comparison of Pharmacokinetics in Healthy Chinese and Japanese Participants.
Autor: | Li X; Department of Clinical Pharmacology, Zhongshan Hospital, Fudan University, Shanghai, China., Haranaka M; Hakata Clinic, Souseikai Global Clinical Research Center, Fukuoka, Japan., Li H; Department of Clinical Pharmacology, Zhongshan Hospital, Fudan University, Shanghai, China., Liu P; Bayer Healthcare Co. Ltd., Clinical Pharmacology Asia, Beijing, China. pei.liu@bayer.com., Chen H; Bayer Healthcare Co. Ltd., Clinical Pharmacology Asia, Beijing, China., Klein S; Bayer AG, Clinical Pharmacology, Berlin, Germany., Reif S; Bayer AG, Clinical Pharmacology, Berlin, Germany., Francke K; Bayer AG, Clinical Pharmacology, Berlin, Germany., Friedrich C; Bayer AG, Clinical Pharmacology, Berlin, Germany., Okumura K; Bayer Yakuhin Ltd., Osaka, Japan. |
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Jazyk: | angličtina |
Zdroj: | Clinical pharmacokinetics [Clin Pharmacokinet] 2024 Jun; Vol. 63 (6), pp. 901-915. Date of Electronic Publication: 2024 Jun 21. |
DOI: | 10.1007/s40262-024-01387-y |
Abstrakt: | Background: Afferent neuronal hypersensitization via P2X3 receptor signaling has been implicated as a driver of several disorders, including refractory chronic cough, endometriosis, diabetic neuropathic pain, and overactive bladder. Eliapixant, a selective P2X3 receptor antagonist, has been in clinical development for all four disorders. Objective: This paper describes pharmacokinetic (PK) and safety data from two phase I studies of eliapixant in healthy Japanese and Chinese participants and compares those data within the two populations and with previous multiple dose data from Caucasian participants. Methods: Two separate phase I, single-center, randomized, placebo-controlled studies were conducted with healthy male participants. The Japanese study was single-blind and the Chinese study was double-blind. Eliapixant was administered as an oral amorphous solid dispersion immediate-release tablet in strengths of 25 mg, 75 mg, and 150 mg. PK characteristics after a single dose (SD) and at steady state (multiple dose [MD], twice daily), adverse events (AEs), and tolerability were evaluated. A post hoc comparison of PK characteristics after SD of eliapixant in Japanese and Chinese participants, and after MD of eliapixant in Japanese, Chinese, and Caucasian participants, was performed. Results: Overall, 36/39 participants enrolled in the Japanese/Chinese studies, respectively (mean [standard deviation] age 25.4 [6.5] and 26.7 [5.0] years, respectively). After SD administration, maximum plasma concentration (C Conclusion: Eliapixant was well tolerated by Japanese and Chinese participants. The inter-ethnic evaluation demonstrated similar PK characteristics across Japanese, Chinese, and Caucasian participants. Registration: ClinicalTrials.gov identifier numbers: NCT04265781 and NCT04802343. (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.) |
Databáze: | MEDLINE |
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