Safety, pharmacokinetics, and pharmacodynamics of GS1-144, a neurokinin-3 recept...

연구 요약

Safety, pharmacokinetics, and pharmacodynamics of GS1-144, a neurokinin-3 receptor antagonist: A randomized phase 1 single and multiple ascending dose and food effect study.

European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 학술지에 발표된 이 연구는 Wu X, Wang J, Yang X 외 연구팀이 수행하였습니다.

이 연구는 'Safety, pharmacokinetics, and pharmacodynamics of GS1-144, a neurokinin-3 receptor antagonist: A randomized phase 1 single and multiple ascending dose and food effect study.'에 대한 과학적 분석을 제공합니다.

핵심 내용

GS1-144 is a neurokinin-3 receptor (NK3R) antagonist in development for treating menopausal vasomotor symptoms (VMS). This first-in-human, randomized phase 1 study (NCT06385158) evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of GS1-144 in healthy Chinese participants following single and multiple ascending doses (SAD/MAD), and food effect (FE). In Part 1 (SAD), GS1-144 (5-90 mg) or placebo was administered to healthy participants. In Part 2 (FE), GS1-144 30 mg was given under fasted and fed conditions in a two-period crossover in healthy participants. In Part 3 (MAD), healthy female participants of childbearing potential and postmenopausal women received GS1-144 (15-120 mg) or placebo once- (q24h) or twice-daily (q12h) fasted for 7 consecutive days. Primary endpoints included safety and tolerability. Secondary and exploratory endpoints included PK, QT/QTc interval changes, and PD (luteinizing hormone [LH] suppression). Overall, 38, 24, and 66 participants were enrolled in Parts 1-3, respectively. GS1-144 was well-tolerated with no serious adverse events (AEs), deaths, or treatment discontinuations. Most AEs were mild and not dose-related. GS1-144 was rapidly absorbed (median Tmax 0.5-2.0 h) with a linear PK profile after single 5-90 mg and multiple 15-120 mg q24h dosing. Mean half-life at steady state was 5.36-5.96 h, with no dose-dependent changes. Dose-dependent LH reductions were observed across 15-120 mg, with consistent effects between 30 mg q12h and 60 mg q24h (MAD). GS1-144 could be administered with or without meals with no clinically significant impact on PK exposure. These results support further clinical development of GS1-144 for the treatment of VMS.

일반인을 위한 해석

구체적인 실천 사항은 담당 의사 또는 약사와 상담하시기 바랍니다.

실천 사항

• 현재 복용 중인 약물이나 영양제에 대해 궁금한 점이 있다면 담당 의사 또는 약사와 상담하시기 바랍니다
• 약물이나 영양제의 용법·용량을 임의로 변경하지 마세요
• 이상 반응이 나타나면 즉시 전문가에게 문의하세요

의사/약사의 전문적 판단을 대체하지 않습니다 (PMID: 41539370)