CDK 4/6 抑制剂 FCN-437c 没有 QTc 延长：针对成年健康受试者的一项专门研究的浓度 QTc 分析结果。
No QTc prolongation with CDK 4/6 inhibitor FCN-437c: results of a concentration-QTc analysis from a dedicated study in adult healthy subjects.
发表日期：2024
作者：
Lin Zhao, Yi Sun, Xiaoran Yang, Ling Tian, Lize Li, Fangfang Wang, Xiaoye Niu, Lei Diao, Haiyan Li
来源：
Frontiers in Pharmacology
摘要：
心脏毒性和QT间期延长是药物退出市场的常见原因。 FCN-437c 是一种口服、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。在健康受试者中进行了一项单中心、双盲、随机和安慰剂对照临床研究，以利用浓度 QTc (C-QTc) 建模方法研究 FCN-437c 的 QTc 延长潜力。 FCN-437c 在 18 名健康受试者中以 300 毫克和 400 毫克的剂量与安慰剂一起单次口服给药。通过 24 小时动态心电图 (ECG) 监测和血样采集。健康受试者中 400 mg 单剂量的 Cmax 与癌症患者稳态时每日 200 mg 治疗剂量的 Cmax 相似。两个剂量组中 Cmax 几何平均值的 ΔΔQTcF 的 90% CI 上限均 <10 ms。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
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 Cmax 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 Cmax 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].Copyright © 2024 Zhao, Sun, Yang, Tian, Li, Wang, Niu, Diao and Li.