■塞美替尼被批准用于治疗有症状的1型神经纤维瘤病(NF1)的儿科患者,多个国家无法手术的丛状神经纤维瘤(PN),包括美国(≥2年)。直到最近,个体必须在禁食状态下每天服用2次司美替尼(BID).这项研究评估了低脂膳食对患有NF1-PN的青少年参与者的司美替尼PK参数和胃肠道(GI)耐受性的影响。
■年龄≥12至<18岁的合格参与者服用25mg/m2司美替尼BID,低脂膳食(T1)28天,接下来是7天的清洗,然后以禁食状态(T2)再给药28天。主要目的是评估在T1和T2中司美替尼多次剂量后,低脂膳食对AUC0-12,ss和GI耐受性的影响。关键次要目标是额外的PK参数和不良事件(AE)。
■在主数据截止时,所有24名参与者完成T1,23名参与者完成T2.T1和T2之间的AUC0-12,ss没有显着差异。在T1和T2,29.2%和33.3%的参与者,分别,报告≥1GIAE。无GI不良事件≥3级或严重不良事件,或GIAE导致治疗中断,停药,或在T1和T2报告剂量减少。
■在NF1-PN青少年中,低脂膳食给药司美替尼对司美替尼AUC0-12、ss和胃肠道耐受性均无临床相关影响。
■NCT05101148。
UNASSIGNED: Selumetinib is approved for the treatment of pediatric patients with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN) in multiple countries, including the USA (≥ 2 years). Until recently, individuals had to take selumetinib twice daily (BID) in a fasted state. This study evaluated the effect of a low-fat meal on selumetinib PK parameters and gastrointestinal (GI) tolerability in adolescent participants with NF1-PN.
UNASSIGNED: Eligible participants aged ≥ 12 to < 18 years took 25 mg/m2 selumetinib BID with a low-fat meal (T1) for 28 days, followed by a 7-day washout, and then administration in a fasted state (T2) for another 28 days. Primary objectives were to evaluate the effect of a low-fat meal on AUC0-12,ss and GI tolerability after multiple selumetinib doses in T1 versus T2. Key secondary objectives were additional PK parameters and adverse events (AEs).
UNASSIGNED: At primary data cut-off, all 24 participants completed T1, and 23 participants completed T2. There were no significant differences in AUC0-12,ss between T1 and T2. In T1 and T2, 29.2% and 33.3% participants, respectively, reported ≥ 1 GI AE. No GI AEs Grade ≥ 3, or serious AEs, or GI AEs resulting in treatment interruptions, discontinuation, or dose reductions were reported in T1 and T2.
UNASSIGNED: Dosing selumetinib with a low-fat meal had no clinically relevant impact on selumetinib AUC0-12,ss nor GI tolerability in adolescents with NF1-PN.
UNASSIGNED: NCT05101148.