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

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Title: An open-label, crossover study to compare different formulations and evaluate effect of food on pharmacokinetics of pimitespib in patients with advanced solid tumors
Authors: Komatsu, Yoshito Browse this author →KAKEN DB
Shimokawa, Tsuneo Browse this author
Akiyoshi, Kohei Browse this author
Karayama, Masato Browse this author
Shimomura, Akihiko Browse this author
Kawamoto, Yasuyuki Browse this author →KAKEN DB
Yuki, Satoshi Browse this author
Tambo, Yuichi Browse this author
Kasahara, Kazuo Browse this author
Keywords: Crossover study
Effect of food
HSP90 inhibitor
Pharmacokinetics
Pimitespib
Advanced solid tumors
Issue Date: 1-Oct-2022
Publisher: Springer
Journal Title: Investigational new drugs
Volume: 40
Issue: 5
Start Page: 1011
End Page: 1020
Publisher DOI: 10.1007/s10637-022-01285-9
Abstract: 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.
Type: article
URI: http://hdl.handle.net/2115/86778
Appears in Collections:北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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