Xu Jia, Liu Jingrui, Ding Yanhua, Yang Xiaoran, Fu Yunjie, Sun Yi
Phase I Clinical Trial Unit, First Hospital, Jilin University, Changchun, China.
AVANC PHARMACEUTICAL CO., LTD, Dongzhou Road, Bixi Street, 215513, Changshu City, Jiangsu, China.
Invest New Drugs. 2025 Jul 15. doi: 10.1007/s10637-025-01552-5.
This study explored the impact of hepatic impairment on the safety and pharmacokinetics (PK) of FCN-437c, a novel dual CDK4/6 inhibitor for potential breast cancer treatment. In an open-label trial, 25 subjects (8 with mild hepatic impairment, 8 with moderate hepatic impairment, and 8 healthy controls matched for age, sex, and body weight) received a single 200-mg dose of FCN-437c. Results showed that FCN-437c was generally well-tolerated, with no serious adverse events. In mild hepatic impairment group, total FCN-437c C increased by 9.5%, while AUC and AUC decreased by 4.8%. Free drug exposure increased by 24.7%, 8.4%, and 8.4%. In moderate hepatic impairment group, total FCN-437c C, AUC, and AUC decreased by 16.7%, 17.1%, and 15.7%, and free drug exposure increased by 47.8%, 47.0%, and 49.6%. Overall, no clinically relevant differences in FCN-437c exposure were found between subjects with mild or moderate hepatic impairment and normal controls, but moderate hepatic impairment increased free drug exposure. Thus, no dose adjustment is needed for patients with mild hepatic impairment, but a reduced dose may be necessary for those with moderate hepatic impairment. Trial Registration: www.clinicaltrials.gov identifier NCT06620731 (retrospectively registered).
本研究探讨了肝损伤对FCN-437c安全性和药代动力学(PK)的影响,FCN-437c是一种用于潜在乳腺癌治疗的新型双重CDK4/6抑制剂。在一项开放标签试验中,25名受试者(8名轻度肝损伤患者、8名中度肝损伤患者以及8名年龄、性别和体重匹配的健康对照)接受了单次200毫克剂量的FCN-437c。结果显示,FCN-437c总体耐受性良好,未出现严重不良事件。在轻度肝损伤组中,FCN-437c的总C增加了9.5%,而AUC和AUC降低了4.8%。游离药物暴露增加了24.7%、8.4%和8.4%。在中度肝损伤组中, FCN-437c的总C、AUC和AUC分别降低了16.7%、17.1%和15.7%,游离药物暴露增加了47.8%、47.0%和49.6%。总体而言,轻度或中度肝损伤受试者与正常对照之间在FCN-437c暴露方面未发现临床相关差异,但中度肝损伤会增加游离药物暴露。因此,轻度肝损伤患者无需调整剂量,但中度肝损伤患者可能需要减少剂量。试验注册:www.clinicaltrials.gov标识符NCT06620731(回顾性注册)