Phase 1 Study Evaluating the Effect of Food and Omeprazole-Induced Gastric pH Ch...

연구 요약

Phase 1 Study Evaluating the Effect of Food and Omeprazole-Induced Gastric pH Change on the Pharmacokinetics and Safety of Imlunestrant in Healthy Females.

Clinical therapeutics 학술지에 발표된 이 연구는 Datta-Mannan A, Shanks E, Yuen E 외 연구팀이 수행하였습니다.

이 연구는 'Phase 1 Study Evaluating the Effect of Food and Omeprazole-Induced Gastric pH Change on the Pharmacokinetics and Safety of Imlunestrant in Healthy Females.'에 대한 과학적 분석을 제공합니다.

핵심 내용

PURPOSE: To assess the effect of low-fat food intake and the effect of a gastric acid reducing agent (omeprazole) on imlunestrant pharmacokinetics (PK), safety, and tolerability. METHODS: A phase 1, open-label cohort study (NCT04840888) in healthy adult females of non-childbearing potential Food effect was evaluated in cohort 1 in which, participants were randomized (1:1) to fasted/fed or fed/fasted crossover treatment sequences and received one dose of 400 mg imlunestrant once-daily in each fed (a low-fat meal; 500 calories, 13% fat) or fasted state with 4 days washout period between doses. Omeprazole's effect was evaluated in cohort 2, in which participants received imlunestrant in fixed treatment sequence with a washout period between doses: (1) a single dose of 400 mg imlunestrant alone on Day 1, (2) no treatment between Day 2-Day 5, (3) 40 mg omeprazole alone once-daily between Day 5-8, and (4) 400 mg imlunestrant + 40 mg omeprazole on Day 9. Blood samples for PK assessments were collected for the evaluation of the areas under the concentration curve AUC(0-96h), AUC(0-∞), maximum observed drug concentration (Cmax), time of maximum observed drug concentration (Τmax); their geometric least squares (GLS) mean ratios were calculated. Safety assessments involved monitoring of adverse events (AEs), clinical chemistry, hematology, vital signs, 12-lead electrocardiogram, and physical examination. FINDINGS: Eight females were enrolled in cohort 1 and 10 in cohort 2. In cohort 1, PK parameters were statistically significantly increased with GLS mean ratios (90% CI): 1.99 (1.67, 2.36) in AUC(0-96h), 2.04 (1.41, 2.94) in AUC(0-∞), and 3.55 (2.83, 4.45) in Cmax, following dosing with imlunestrant in the fed state compared to the fasted state. The change in Τmax was not statistically significant. In cohort 2, the change in PK parameters of imlunestrant when dosed alone and in the presence of the PPI omeprazole were not statistically significant and were comparable. Imlunestrant was well tolerated, and no clinically meaningful findings were recorded in either cohort. IMPLICATIONS: Low-fat food intake resulted in increases of ∼2-fold in AUC and ∼3.6-fold in Cmax. Therefore, patients will be instructed to abstain from food consumption two hours before and one hour after taking imlunestrant. Concomitant use of imlunestrant and omeprazole displayed a low risk of drug-drug interaction, therefore imlunestrant may be taken with a proton pump inhibitor such as omeprazole. A single oral dose of 400 mg imlunestrant was generally well tolerated in healthy females regardless of food or omeprazole intake.

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