Phase I clinical trial of safety comparison between the generic and the original regorafenib tablets
10.3760/cma.j.cn114015-20220224-00149
- VernacularTitle:仿制与原研瑞戈非尼片安全性比较的Ⅰ期临床试验
- Author:
Yuanxu TONG
1
;
Yan LI
1
;
Yali WEI
1
;
Lu QI
1
;
Chen LIU
1
;
Shuang LI
1
;
Xinghe WANG
1
Author Information
1. 首都医科大学附属北京世纪坛医院药物Ⅰ期临床试验研究室，北京 100038
- Publication Type:Journal Article
- Keywords:
Clinical trial, phase I;
Comparative study;
Safety;
Regorafenib
- From:
Adverse Drug Reactions Journal
2022;24(6):308-313
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To compare the safety of the generic and the original regorafenib tablets.Methods:Two single center, randomized, open-label, 2-period self-crossover phase I clinical trials (single dose) were conducted under fasting condition and with low-fat meal respectively in healthy adult volunteers. The test preparation (T) of regorafenib was produced by Beijing Sl Pharmaceutical Co.,Ltd. and the reference preparation (R) was produced by Bayer HealthCare Pharmaceuticals Inc. In the 2 trials, male healthy subjects were randomly divided into 2 groups, respectively, and took 2 times of the preparations with different order in each group, which were R-T group (subjects took R on day 1 and then T on day 13) and T-R group (subjects took T on day 1 and then R on day 13). The subjects took drugs under fasting condition and with low-fat meal in the 2 trials respectively. After medication, vital signs detection, electrocardiogram, general physical examination, blood routine, blood biochemical, coagulation function, and other tests were performed regularly, and the occurrence of adverse events (AEs) were recorded and the severity of AEs was assessed.Results:Sixty-four subjects were enrolled in the trial under fasting condition, including 32 in the T-R group and 32 in the R-T group, and the safety data was obtained from 61 and 57 subjects taking T and R, respectively. Seventy-six subjects were included in the postprandial trial, including 38 in the T-R group and 38 in the R-T group, and the safety data was obtained from 74 subjects taking T and R, respectively. In the 2 trials, there was no significant difference in the incidence of AEs between subjects taking T and those taking R [41.0% (25/61) vs. 31.6% (18/57), χ2=1.125, P=0.289; 56.8% (42/74) vs. 45.9% (34/74), χ2=0.183, P=0.188]. A total of 230 AEs occurred in the 2 trials, of which 228 cases were grade 1 (99.1%, 131 and 97 AEs occurred in subjects taking T and R, respectively), 2 cases were grade 2 (0.9%, 1 AE occurred in subjects taking T and R, respectively), and no grade ≥ 3 AEs occurred. The types of AEs occurred in the 2 trials were the same, of which bradycardia was the most common, followed by prolonged QT interval of ECG. All ECG abnormalities were found during routine examinations, and no subjects had obvious clinical symptoms. Conclusion:The safety of the generic and the original regorafenib tablets was consistent after a single dose administration under fasting condition and with low-fat meal.
