Hu Linlin, Cai Mingmin, Qian Wei, Dou Ting, Sun Qiuyue, Tang Lu, Wang Huiping
Office of Clinical Trial Institution, School of Medicine, Nanjing Zhongda Hospital, Southeast University, Nanjing, 210009, China.
Department of Phase I Clinical Trial Unit, School of Medicine, Nanjing Zhongda Hospital, Southeast University, Nanjing, 210009, China.
Invest New Drugs. 2022 Dec;40(6):1274-1281. doi: 10.1007/s10637-022-01299-3. Epub 2022 Sep 10.
To evaluate the potential gastric pH-dependent drug-drug interaction (DDI), safety and tolerability of famitinib co-administered with omeprazole in healthy subjects. Twenty healthy subjects were enrolled in a single-center, single-arm, open-label, fixed-sequence study. Famitinib was administered as a single oral 25 mg under a fasting condition on day 1, omeprazole (40 mg once daily) was given on days 10-14, concomitantly with famitinib on day 15, and for the follow-up 7 additional days (days 16-22). Blood samples were collected for the pharmacokinetic analysis of famitinib and its metabolite SHR116637 following each famitinib dose. Safety and tolerability were assessed during the whole progress via clinical laboratory tests. The least-squares geometric mean ratios (GMRs) (90% CI) of C, AUC and AUC for famitinib combined with omeprazole to famitinib alone were 0.989 (0.953, 1.027), 0.956 (0.907, 1.007) and 0.953(0.905, 1.005) respectively. For the metabolite SHR116637, their GMRs (90% CI) of the above parameters were 0.851 (0.786, 0.920), 0.890 (0.838, 0.946)and 0.887 (0.835, 0.943), indicating the absence of significant differences in the parameters. During the treatment period, 9(45%) subjects reported 16 treatment emergent adverse events (TEAE), among which 6 subjects (30%) reported 9 TEAEs and 1 subject (5%) reported 1 TEAE during famitinib or omeprazole administered alone respectively, 5 subjects (25.0%) reported 6 TEAEs during in the combined administration phase. Omeprazole did not have a significant influence on the pharmacokinetics (PK) of famitinib and SHR116637, and the safety profile was good upon co-administration. ClinicalTrials.gov identifier NCT 05,041,920.
评估在健康受试者中，法米替尼与奥美拉唑联合使用时潜在的胃pH值依赖性药物相互作用（DDI）、安全性和耐受性。20名健康受试者参加了一项单中心、单臂、开放标签、固定顺序研究。第1天，法米替尼在空腹条件下口服单剂量25mg；第10 - 14天给予奥美拉唑（40mg每日一次），第15天与法米替尼同时给药，并持续随访7天（第16 - 22天）。每次给予法米替尼后采集血样，用于法米替尼及其代谢产物SHR116637的药代动力学分析。通过临床实验室检测在整个过程中评估安全性和耐受性。法米替尼与奥美拉唑联合使用时，法米替尼的C、AUC和AUC的最小二乘几何平均比值（GMRs）（90%CI）分别为0.989（0.953，1.027）、0.956（0.907，1.007）和0.953（0.905，1.005）。对于代谢产物SHR116637，上述参数的GMRs（90%CI）分别为0.851（0.786，0.920）、0.890（0.838，0.946）和0.887（0.835，0.943），表明参数无显著差异。治疗期间，9名（45%）受试者报告了16例治疗期间出现的不良事件（TEAE），其中6名受试者（30%）在单独使用法米替尼或奥美拉唑期间分别报告了9例TEAE，1名受试者（5%）报告了1例TEAE，5名受试者（25.0%）在联合给药阶段报告了6例TEAE。奥美拉唑对法米替尼和SHR116637的药代动力学（PK）没有显著影响，联合给药时安全性良好。ClinicalTrials.gov标识符：NCT 05,041,920。
