2.1 Trial design and subjects
This single-center, open-label, phase I trial was designed to primarily assess the effect of multiple oral doses of rifampin on the pharmacokinetics of a single oral dose of SHR2554 in healthy Chinese volunteers. Secondly, we assessed the tolerance and safety of the SHR2554 administration alone and when coadministration with rifampin in Chinese healthy volunteers.
The subjects enrolled should age 18 to 45 years (including both ends) with body mass index (BMI) in the range of 19.0-26.0 kg/m2 (including the critical value), the body weight of male subjects less than 50 kg or that of female subjects less than 45 kg would be excluded. All inclusion and exclusion criteria were provided in the supplementary.
The qualified subjects were admitted to the phase I clinical trial center on D-0, provided light dinner, and fasted but no water for 10 hours. On D1, the subjects were orally administrated SHR2554 at a dose of 300mg; then, all subjects were orally administrated rifampin 600mg quaque die (QD) for 8 days (D4-D9, D12). On D-11, 300mg SHR2554 and 600mg rifampin were orally co-administrated under fasting conditions with 240ml water. Water was forbidden before or after 1 hour, and food was forbidden after 4 hours of administration. The blood samples were collected before administration 60 mins, and 0.5h,1.0h,1.5h,2.0h,2.5h,3.0h,4.0h,6.0h,8.0h,12.0h,24.0h,48.0h after first SHR2554 administration on day 1 and day 11. All subjects were discharged after examination on D-13 and received follow-up visits on D-16 to D-19. The clinical progress is shown in Figure 1 .
The study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice (GCP) and approved by the Institutional Ethics Committee of Xiangya Hospital. Written informed consent was obtained from all subjects prior to the screening. This study was registered at