scholarly journals A first‐in‐human, randomized, double‐blind, single‐ and multiple‐dose, phase I study of recombinant human thymosin β4 in healthy Chinese volunteers

Author(s):  
Xinghe Wang ◽  
Long Liu ◽  
Lu Qi ◽  
Chunpu Lei ◽  
Pu Li ◽  
...  
2020 ◽  
Vol 11 ◽  
Author(s):  
Jingrui Liu ◽  
Binhua Lv ◽  
Hewen Yin ◽  
Xiaoxue Zhu ◽  
Haijing Wei ◽  
...  

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.


2013 ◽  
Vol 53 (4) ◽  
pp. 385-395 ◽  
Author(s):  
Fabrice Balavoine ◽  
Michel Azizi ◽  
Damien Bergerot ◽  
Nadia De Mota ◽  
Rémi Patouret ◽  
...  

2018 ◽  
Vol 40 (5) ◽  
pp. 719-732.e1
Author(s):  
Tommy Tsang Cheung ◽  
Joanne Wing Yan Chiu ◽  
Man Fung Yuen ◽  
Karen Siu Ling Lam ◽  
Bernard Man Yung Cheung ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document