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European Journal of Drug Metabolism and Pharmacokinetics

Erschienen in:

01.07.2022 | Original Research Article

An Open Label, Phase 1, Randomized, Seven-treatment, Seven-period, Crossover Study to Assess the Relative Bioavailability, pH Effect, Food Effect, and Dose Proportionality of CC-292, a Potent and Orally Available Bruton’s Tyrosine Kinase Inhibitor

verfasst von: Yiming Cheng, Liangang Liu, Yongjun Xue, Simon Zhou, Yan Li

Erschienen in: European Journal of Drug Metabolism and Pharmacokinetics | Ausgabe 4/2022

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Abstract

Background and Objective

CC-292 is a potent, selective, orally administered small molecule inhibitor of Bruton’s tyrosine kinase (BTK). To support the clinical investigation of CC-292, a randomized, seven-treatment, seven-period, crossover study was conducted to assess the relative bioavailability, pH effect, food effect, and dose-proportionality of two formulated tablets of CC-292.

Methods

Healthy subjects (n = 24) were enrolled in the study and randomly assigned into different treatment sequences. Blood samples were collected at pre-specified time points to measure the drug concentrations in plasma. Statistical analyses were performed to compare the pharmacokinetics of CC-292 under different conditions.

Results

The relative bioavailability of the newly developed formulation [spray-dried dispersion (SDD)] to the reference formulation (P22) was 1.24. When a single dose of CC-292 SDD tablet was administered under fed conditions, the area under the plasma concentration–time curve from time zero to infinity (AUC_∞) increased by 10.9% and the maximum plasma drug concentration C_max) decreased by 19.4% compared to when CC-292 was administered under fasted conditions. When a single dose of CC-292 SDD tablet was administered after multiple doses of omeprazole, the area under the plasma concentration–time curve from time zero to infinity (AUC_∞) decreased by 36.8% and the maximum plasma drug concentration C_max) decreased by 48.1% compared to when CC-292 was administered alone. Over a dose range of 100–300 mg (SDD formulation), CC-292 exhibited more than dose-proportional increases of drug exposures.

Conclusions

CC-292 was well tolerated when administered to healthy subjects as single oral doses under all conditions. Food intake had no clinically relevant impact on CC-292 pharmacokinetics compared to fasted conditions. Therefore, CC-292 can be administered with or without food. Co-administration of CC-292 with multiple doses of omeprazole (40 mg) decreased the pharmacokinetic exposure of CC-292. However, the effect was not clinically relevant.

Clinical Trials Registration

NCT02433457

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Titel: An Open Label, Phase 1, Randomized, Seven-treatment, Seven-period, Crossover Study to Assess the Relative Bioavailability, pH Effect, Food Effect, and Dose Proportionality of CC-292, a Potent and Orally Available Bruton’s Tyrosine Kinase Inhibitor
verfasst von: Yiming Cheng
Liangang Liu
Yongjun Xue
Simon Zhou
Yan Li
Publikationsdatum: 01.07.2022
Verlag: Springer International Publishing
Erschienen in: European Journal of Drug Metabolism and Pharmacokinetics / Ausgabe 4/2022
Print ISSN: 0378-7966
Elektronische ISSN: 2107-0180
DOI: https://doi.org/10.1007/s13318-022-00776-7

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An Open Label, Phase 1, Randomized, Seven-treatment, Seven-period, Crossover Study to Assess the Relative Bioavailability, pH Effect, Food Effect, and Dose Proportionality of CC-292, a Potent and Orally Available Bruton’s Tyrosine Kinase Inhibitor

Abstract

Background and Objective

Methods

Results

Conclusions

Clinical Trials Registration

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Background and Objective

Methods

Results

Conclusions

Clinical Trials Registration

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