An open-label, crossover study to compare different formulations and evaluate effect of food on pharmacokinetics of pimitespib in patients with advanced solid tumors

Komatsu, Yoshito; Shimokawa, Tsuneo; Akiyoshi, Kohei; Karayama, Masato; Shimomura, Akihiko; Kawamoto, Yasuyuki; Yuki, Satoshi; Tambo, Yuichi; Kasahara, Kazuo

An open-label, crossover study to compare different formulations and evaluate effect of food on pharmacokinetics of pimitespib in patients with advanced solid tumors

Komatsu, Yoshito; Shimokawa, Tsuneo; Akiyoshi, Kohei et al.

Investigational new drugs, 2022, 40(5), 1011-1020

Permalink : https://hdl.handle.net/2115/86778

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https://doi.org/10.1007/s10637-022-01285-9			11

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アクセス権	open access
URI	https://hdl.handle.net/2115/86778
タイトル	An open-label, crossover study to compare different formulations and evaluate effect of food on pharmacokinetics of pimitespib in patients with advanced solid tumors
著者	Komatsu, Yoshito ; Shimokawa, Tsuneo ; Akiyoshi, Kohei ; Karayama, Masato ; Shimomura, Akihiko ; Kawamoto, Yasuyuki ; Yuki, Satoshi ; Tambo, Yuichi ; Kasahara, Kazuo
e-Rad_Researcher 60333598 著者名 Komatsu, Yoshito
著者名 Shimokawa, Tsuneo
著者名 Akiyoshi, Kohei
著者名 Karayama, Masato
著者名 Shimomura, Akihiko
e-Rad_Researcher 60755601 著者名 Kawamoto, Yasuyuki
著者名 Yuki, Satoshi
著者名 Tambo, Yuichi
著者名 Kasahara, Kazuo
言語	英語
キーワード	Crossover study
	Effect of food
	HSP90 inhibitor
	Pharmacokinetics
	Pimitespib
	Advanced solid tumors
発行日	2022-10-01
出版者	Springer
収録物名	Investigational new drugs
巻(号)	40(5)
ページ	1011-1020
抄録	This study compared the bioavailability of two pimitespib formulations (Formulations A and B), evaluated the food effect on Formulation A, and evaluated the safety and efficacy of multiple pimitespib doses in patients with solid tumors. This clinical, pharmacological multicenter study had two cohorts and periods. A single dose of Formulation A or B was administered in a crossover design to compare the pharmacokinetics in Cohort 1. In Cohort 2, the effects of fed vs fasting conditions were evaluated among those receiving Formulation A. Subsequently, multiple Formulation A doses were administered to all patients for safety and efficacy assessments. In Cohorts 1 and 2, 12 and 16 patients, respectively, were analyzed for pharmacokinetics. Thirty patients were analyzed for safety and efficacy. Maximum concentration (C-max), area under the curve (AUC)(last), and AUC(inf) geometric mean ratios for Formulations A and B (90% confidence interval [CI]) were 0.8078 (0.6569-0.9933), 0.7973 (0.6672-0.9529), and 0.8094 (0.6697-0.9782), respectively; 90% CIs were not within the bioequivalence range (0.80-1.25). In Cohort 2, mean C-max, AUC(last), and AUC(inf) were higher in fed vs fasting conditions. No safety concerns emerged with single or multiple administration. Overall response rate, disease control rate, and median progression-free survival were 0%, 33%, and 1.5 months, respectively. Four patients had stable disease >= 5 months. Bioequivalence of the two formulations was unconfirmed. Systemic exposure of Formulation A was approximately 20% less than Formulation B. A high-fat/calorie meal increased the relative pharmacokinetics and bioavailability of a single 160-mg dose. Trial Registration: JapicCTI-184191 (Japan Pharmaceutical Information Center) registered on November 5, 2018.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
PISSN	0167-6997
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1007/s10637-022-01285-9