布雷哌唑口服溶膜：一项随机、开放标签、单剂量、跨界的中国健康志愿者生物等效性研究。

IF 3.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Clinical therapeutics Pub Date : 2025-09-01 DOI:10.1016/j.clinthera.2025.07.001

Tian Wang MM , Lei Shang MS , Yingxia He PhD , Liyin Guo MM , Xiaoyun Ruan MS , Pan Han MS , Wangping Wu BS , Min Chen BS , Fei Zhang BS , Cailu Hu BS , Jue Liu PhD

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引用次数: 0

摘要

目的：Brexpiprazole oral soluble film （OSF）是一种临床开发中的用于治疗成人精神分裂症的新剂型。本研究旨在探讨brexpiprazole osf2mg与brexpiprazole口腔崩解片（ODT） 2mg （Rexulti®OD）在中国健康成人体内的生物等效性、安全性和耐受性。方法：采用单中心、随机、开放标签、单剂量的交叉研究，包括空腹条件下的六序列三期交叉干预和餐后条件下的两序列两期交叉干预。brexpiprazole的药代动力学采样在给药72小时后进行，并有28天的洗脱期。在整个研究过程中，对参与者进行了任何不良事件的监测。采用线性混合效应模型对0 ~ 72h的最大血浆浓度（Cmax）和血浆浓度-时间曲线下面积（AUC）（AUC0-72h）进行统计学分析，进行生物等效性评价。结果：在禁食试验中，30名符合条件的个体被招募并完成了研究。与不加水给药brexpiprazole odt2mg相比，不加水和加水给药brexpiprazole osf2mg的Cmax和AUC0-72h的几何平均比值均接近100%，相应的90%置信区间均在80.00-125.00%的既定生物等效性限内。在餐后试验中，26名参与者被随机分配，2名参与者在洗脱期退出研究。brexpiprazole OSF和odt2mg的Cmax和auc0 ~ 72h的生物等效性范围均在80.00 ~ 125.00%之间。总的来说，两种布雷吡拉唑的配方显示出相当的安全性，在研究期间没有严重或意外的不良事件报告。结论：Brexpiprazole osf2mg与Brexpiprazole odt2mg具有生物等效性，在空腹和餐后条件下具有良好的安全性、耐受性和可接受性。由于易于给药，brexpiprazole osf2mg有望改善药物依从性，并为精神分裂症患者提供可行的治疗选择。

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Brexpiprazole Oral Soluble Film: A Randomized, Open-Label, Single-Dose, Crossover Bioequivalence Study in Healthy Chinese Volunteers

Purpose

Brexpiprazole oral soluble film (OSF) is a novel dosage form under clinical development indicated for the treatment of schizophrenia in adults. This study aimed to investigate the bioequivalence, safety and tolerability of brexpiprazole OSF 2 mg compared with brexpiprazole orally disintegrating tablet (ODT) 2 mg (Rexulti®OD) in healthy Chinese adults.

Methods

A single-center, randomized, open-label, single-dose, crossover study was conducted, including a six-sequence three-period crossover intervention under fasting condition and a two-sequence two-period crossover intervention under postprandial condition. Pharmacokinetic sampling for brexpiprazole was carried out until 72 hours after dosing with a 28-day washout period. Participants were monitored for any adverse events throughout the study. The maximum plasma concentration (C_max) and the area under the plasma concentration-time curve (AUC) from time 0 to 72 hours (AUC_0-72h) were statistically analyzed using a linear mixed-effects model for bioequivalence evaluation.

Findings

In the fasting trial, 30 eligible individuals were enrolled and completed the study. Compared to brexpiprazole ODT 2 mg administered without water, the geometric mean ratios for C_max and AUC_0-72h of brexpiprazole OSF 2 mg taken without or with water were all close to 100%, and the corresponding 90% confidence intervals were within the established bioequivalence limit of 80.00–125.00%. In the postprandial trial, 26 participants were randomized and 2 participants withdrew from the study during the washout period. The bioequivalence range of C_max and AUC_0-72h for brexpiprazole OSF and ODT 2 mg administered without water were both within 80.00–125.00%. Generally, both formulations of brexpiprazole displayed comparable safety profiles, with no serious or unexpected adverse events reported during the study.

Implications

Brexpiprazole OSF 2 mg is bioequivalent to brexpiprazole ODT 2 mg with favorable safety, tolerability and acceptability under fasting and postprandial conditions. Due to its ease of administration, brexpiprazole OSF 2 mg may be expected to improve medication adherence, and provide a viable treatment option for patients with schizophrenia.

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来源期刊

Clinical therapeutics 医学-药学

CiteScore

6.00

自引率

3.10%

发文量

154

审稿时长

9 weeks

期刊介绍： Clinical Therapeutics provides peer-reviewed, rapid publication of recent developments in drug and other therapies as well as in diagnostics, pharmacoeconomics, health policy, treatment outcomes, and innovations in drug and biologics research. In addition Clinical Therapeutics features updates on specific topics collated by expert Topic Editors. Clinical Therapeutics is read by a large international audience of scientists and clinicians in a variety of research, academic, and clinical practice settings. Articles are indexed by all major biomedical abstracting databases.