Background: Jaktinib is a novel selective janus kinase 1/2 inhibitor. The phase I first-in-human study evaluated the tolerance and pharmacokinetics of jaktinib in healthy Chinese subjects.Methods: A randomized, double-blind, placebo-controlled study were designed. A total of 126 healthy subjects were enrolled into the single ascending dose, multiple ascending dose and food effect study. Safety endpoints included adverse events, abnormal vital signs, 12-lead ECGs, abdominal ultrasound, chest x-ray, physical examination and clinical laboratory tests. Blood, urine and feces samples were collected at predetermined time points for pharmacokinetic analysis of jaktinib, the metabolites ZG0244 and ZG0245, which are formed by oxidation or hydrolysis metabolic pathway, respectively.Results: Jaktinib was absorbed with a median time to peak plasma concentration of 1.25–3.5 h and was eliminated with a half-life of 2.952–9.040 h. Linear pharmacokinetic characteristic was presented over the dose range from 25 to 400 mg. No obvious accumulation was observed after multiple doses for 10 days. Administration after a high-fat breakfast significantly increased the absorption of jaktinib. The accumulated fraction of jaktinib and the determined metabolites excreted in urine and feces was 19.478%. Jaktinib was well tolerated in all single dose cohorts. In multiple dose cohorts, 200 mg q24 h method was evaluated as maximally tolerated dose. Neutropenia, diarrhea, dizziness and headache were the most frequently reported treatment related adverse events. No deaths, serious or Grade ≥4 adverse events was developed.Conclusion: Jaktinib was well tolerated when single dose ranging from 25 to 400 mg and multiple dose up to 200 mg q24 h. The safety and pharmacokinetic characteristics support the next trial in myelofibrosis patients.
Safety, Tolerability, Pharmacokinetics, and Food Effects on TAC‐302 in Healthy Participants: Randomized, Double‐Blind, Placebo‐Controlled, Single‐Dose and Multiple‐Dose Studies
