Objective: This study was conducted to investigate the safety, tolerability and pharmacokinetics (PK) of WXFL10203614 after single and multiple oral doses in healthy Chinese subjects.Methods: A single-center, randomized, double-blind, placebo-controlled phase Ⅰ study was performed on healthy Chinese subjects. In the single-dose study, Subjects were randomized into 7 dose levels of WXFL10203614 (1 mg group, n = 2; 2, 5, 10, 17, 25 and 33 mg groups with placebo, 8 subjects per group, 2 of them given placebo). In the multiple-dose study, subjects received 5 or 10 mg WXFL10203614 once daily (QD), 5 mg twice daily (BID) or placebo for 7 consecutive days. Safety, tolerability and PK of WXFL10203614 were all assessed.Results: A total of 592 subjects were screened, 50 subjects were enrolled in the single-dose study and 30 in the multiple-dose study. All adverse events (AEs) were mild or moderate and resolved spontaneously. No Serious Adverse Events (SAEs) or deaths were reported during the study. WXFL10203614 was absorbed rapidly after dosing with Tmax of 0.48–0.98 h, Cmax, AUC0-t and AUC0-∞ were all increased in a dose-related manner over the range of 1–33 mg. Renal excretion was the major route of elimination of WXFL10203614. Steady-state PK parameters (Cmax,ss, AUC0-t,ss and AUC0-∞,ss) were elevated after once-daily administration of 5–10 mg WXFL10203614 and non- and weak drug accumulations were observed, whereas moderate drug accumulation occurred in the 5 mg BID group.Conclusion: WXFL10203614 exhibited good safety, tolerability and favorable PK profiles in healthy Chinese subjects, supporting further clinical development in patients with rheumatoid arthritis.Clinical Trials Registration Number:http://www.chinadrugtrials.org.cn/index.html, #CTR20190069 and CTR20200143.

Objective: This study was performed to investigate the effect of food on the pharmacokinetics (PK) of WXFL10203614 in healthy Chinese subjects.Methods: This was a randomized, open-label, single-dose, two-treatment (fed vs fasted), two-period, two-sequence, crossover study. 14 eligible subjects were averagely randomized into 2 sequences and then received 10 mg WXFL10203614 under fasted or fed condition. In each period, the blood samples were collected from 0 h (pre-dose) and serially up to 72 h post-dose, and plasma concentrations were detected using the high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method. The effect of food on the PK profile and safety of WXFL10203614 were assessed.Results: 70 subjects were screened, and 14 subjects (10 male and 4 female) were enrolled and completed the study. Under the fasted condition, WXFL10203614 was absorbed rapidly with a Tmax of 0.98 h. The absorption rate was slower, Tmax delayed by 2.98 h, and the Cmax decreased by 16.3% when WXFL10203614 administered after the high-fat and high-calorie diet, other PK parameters were not affected. The 90% confidence intervals (CIs) for the ratio (fed/fasted) of geometric means of the Cmax, AUC0-t and AUC0-∞ were 0.73–1.01, 0.90–1.03 and 0.90–1.03, indicating that the high-fat and high-calorie diet might impact the absorption process of WXFL10203614. Although the Cmax was slightly decreased, there was no significant difference in the Cmax under fasted and fed conditions. Thus, it was not considered clinically significant owing to the small magnitude of changes in Cmax. All Treatment-emergent adverse events (TEAEs) were mild and resolved spontaneously without treatment.Conclusion: Food had no clinically relevant effects on drug system exposure of WXFL10203614. It was well tolerated under fasted and fed conditions in healthy Chinese subjects, so WXFL10203614 could be administered orally with or without food.Clinical Trial Registration: http://www.chinadrugtrials.org.cn/index.html, identifier CTR20191636.