Frontiers in pharmacology · 2026
Safety, tolerability, pharmacokinetics, and pharmacodynamics of LW402, a preferential Janus kinase 1 inhibitor in healthy volunteers: a randomized, double-blinded, placebo-controlled phase 1 trial.
Клиническое исследованиеСтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Gui Yuzhou, Jiang Fan, Xin Liang, Wang Zhe, Zhu Huijuan, Liu Yanmei, Chen Qian, Jia Jingying, Liu Yun
Аннотация
INTRODUCTION: This clinical trial aimed to assess the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of LW402, a preferential JAK1 inhibitor, in healthy participants, so as to provide support for its further development in treating autoimmune diseases.
METHODS: The study included two phases: a single ascending dose (10-400 mg) with 54 participants and a multiple ascending dose (50-150 mg, b.i.d for 6 days plus a single dose on day 7) with 36 participants. Safety, PK (from timed blood samples), and PD (JAK1/JAK2 signaling) were evaluated.
RESULTS: No serious adverse events were reported; only mild treatment-emergent adverse events (TEAEs), such as sinus bradycardia and gastrointestinal issues, occurred. LW402 was rapidly absorbed (median tmax: 0.42-1.0 hours), with slightly super-proportional exposure and minimal accumulation, and preferentially inhibited JAK1-mediated signaling.
DISCUSSION: LW402's favorable safety profile, predictable PK characteristics, and selective JAK1 inhibition collectively support its continued development for the treatment of autoimmune diseases.
CLINICAL TRIAL REGISTRATION: http://www.chinadrugtrials.org.cn, identifier CTR20201897.
METHODS: The study included two phases: a single ascending dose (10-400 mg) with 54 participants and a multiple ascending dose (50-150 mg, b.i.d for 6 days plus a single dose on day 7) with 36 participants. Safety, PK (from timed blood samples), and PD (JAK1/JAK2 signaling) were evaluated.
RESULTS: No serious adverse events were reported; only mild treatment-emergent adverse events (TEAEs), such as sinus bradycardia and gastrointestinal issues, occurred. LW402 was rapidly absorbed (median tmax: 0.42-1.0 hours), with slightly super-proportional exposure and minimal accumulation, and preferentially inhibited JAK1-mediated signaling.
DISCUSSION: LW402's favorable safety profile, predictable PK characteristics, and selective JAK1 inhibition collectively support its continued development for the treatment of autoimmune diseases.
CLINICAL TRIAL REGISTRATION: http://www.chinadrugtrials.org.cn, identifier CTR20201897.