Pharmacokinetics and Safety Evaluation of Maribavir in Healthy Japanese and Matched White Participants: A Phase 1, Open-Label Study.
cytomegalovirus
ethnicity
maribavir
pharmacokinetics
race
safety
Journal
Clinical pharmacology in drug development
ISSN: 2160-7648
Titre abrégé: Clin Pharmacol Drug Dev
Pays: United States
ID NLM: 101572899
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
received:
08
11
2022
accepted:
21
02
2023
medline:
2
6
2023
pubmed:
11
4
2023
entrez:
10
4
2023
Statut:
ppublish
Résumé
This phase I study compared pharmacokinetics and safety of maribavir in Japanese and White participants, and evaluated dose proportionality in Japanese participants. Under fasting conditions, 12 healthy adult participants of Japanese descent and 12 matched White participants received a single 400-mg dose of maribavir. Japanese participants received 2 further doses of maribavir: 200 mg and 800 mg, or 800 mg and 200 mg, separated by a ≥72-hour washout period. Serial blood samples were collected up to 24 hours after dosing for pharmacokinetic assessments. Following the 400-mg dose, the geometric mean ratios (90% confidence interval) of Japanese versus White participants were 110% (91.7%-133%) for maximum plasma concentration, 122% (96.8%-155%) for area under the plasma concentration-time curve (AUC) from time of dosing to the last measurable concentration, and 125% (98.0%-160%) for AUC extrapolated to infinity. In Japanese participants, maribavir AUC extrapolated to infinity and AUC from time of dosing to the last measurable concentration increased in a dose-proportional fashion over 200-800 mg; maximum plasma concentration increased less than dose proportionally. Seven participants reported treatment-emergent adverse events (TEAEs; Japanese participants, 400 mg: 2 [16.7%], 200 mg: 1 [8.3%]; White participants, 400 mg: 4 [33.3%]), all mild and most commonly dysgeusia. No serious TEAEs or TEAEs leading to discontinuation were reported. This study demonstrated higher maribavir systemic exposure in Japanese than White participants and similar safety outcomes. This difference in exposure is not considered clinically important and its significance remains to be determined.
Substances chimiques
maribavir
PTB4X93HE1
Antiviral Agents
0
Dichlororibofuranosylbenzimidazole
53-85-0
Types de publication
Clinical Trial, Phase I
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
645-654Informations de copyright
© 2023 Takeda Development Center Americas, Inc. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.
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