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.