Zhao Lin, Sun Yi, Yang Xiaoran, Tian Ling, Li Lize, Wang Fangfang, Niu Xiaoye, Diao Lei, Li Haiyan
Department of Drug Clinical Trial Center, Peking University Third Hospital, Haidian, Beijing, China.
Shanghai Fosun Pharmaceutical Development Co. Ltd., Shanghai, China.
Front Pharmacol. 2024 Aug 12;15:1433663. doi: 10.3389/fphar.2024.1433663. eCollection 2024.
Cardiotoxicity and QT interval prolongation have been a common cause of withdrawal of drugs from the market. FCN-437c is an oral, second-generation, potent, and selective CDK4/6 inhibitor for the treatment of patients with HR+/HER2- metastatic breast cancer. A single-center, double-blind, randomized, and placebo-controlled clinical study in healthy subjects was conducted to investigate the QTc prolongation potential of FCN-437c utilizing Concentration-QTc (C-QTc) modeling approach. FCN-437c was administered at doses of 300, and 400 mg with single oral administration, along with placebo, in 18 healthy subjects. Electrocardiograms (ECGs) through 24 h holter monitor and blood samples were collected. The C of 400 mg single dose in healthy subjects is similar to that from therapeutic dose 200 mg QD at steady state in patients with cancer. The 90% CI upper limit of ΔΔQTcF at the C geometric mean in both dose groups were <10 ms. It is concluded that FCN-437c has low risk of prolonging the QT interval at therapeutic dose.
https://clinicaltrials.gov/study/NCT06290466?term=NCT06290466&rank=1, identifier [NCT06290466].
心脏毒性和QT间期延长一直是药物撤市的常见原因。FCN - 437c是一种口服的第二代强效选择性CDK4/6抑制剂，用于治疗HR + /HER2 - 转移性乳腺癌患者。在健康受试者中开展了一项单中心、双盲、随机、安慰剂对照的临床研究，采用浓度 - QTc（C - QTc）建模方法研究FCN - 437c延长QTc的可能性。18名健康受试者接受了300毫克和400毫克剂量的FCN - 437c单次口服给药，同时服用安慰剂。通过24小时动态心电图监测收集心电图（ECG）并采集血样。健康受试者中400毫克单剂量的C与癌症患者稳态下每日200毫克治疗剂量的C相似。两个剂量组C几何均值时ΔΔQTcF的90%CI上限均<10毫秒。结论是，FCN - 437c在治疗剂量下延长QT间期的风险较低。
https://clinicaltrials.gov/study/NCT06290466?term=NCT06290466&rank=1，标识符[NCT06290466] 。
