The Pharmacokinetics, Pharmacodynamics, Tolerability, and Safety of Orally Dosed QY201, a Novel JAK1/TYK2 Inhibitor, in Chinese Healthy Subjects.

Abstract

QY201 is a dual inhibitor targeting Janus Kinase 1/Tyrosine Kinase 2, developed for the treatment of atopic dermatitis and other autoimmune diseases. The pharmacokinetics (PK), pharmacodynamics (PD), tolerability, and safety of QY201 were assessed in a randomized, double-blind study in healthy subjects. Population PK and PD models were developed to characterize the PK and PD of QY201. QY201 was absorbed and eliminated rapidly, and the exposure was approximately dose-proportional over the 1-40 mg dose range, with no significant accumulation after repeated dosing. A high-fat meal reduced the maximum plasma concentration of QY201 by 40.7% but did not affect the area under the concentration-time curve. The fraction of the QY201 dose eliminated in the urine unchanged was 22%. In the multiple ascending-dose phase, the reduction of hypersensitive C-reactive protein (hsCRP) and absolute neutrophil count (ANC) showed dose-dependent trends within certain doses. The PK of QY201 was best described by a 2-compartment model with first-order absorption and elimination. The hsCRP was best described by an indirect response maximum drug effect (E_max) model. QY201 was generally safe and well tolerated following oral administration, with dose-limiting toxicity of the highest tested dose of 40 mg being well tolerated. The favorable PK, PD, safety, and tolerability results from these studies supported evaluations of QY201 in future clinical trials.