Work

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

Year: 2026

Type: article

Study designs: Randomized Controlled Trial, Clinical Trial

Abstract: • First-in-human study of GS1-144 in healthy Chinese participants • Evaluated safety, PK, PD, food effect, and QTc in SAD, MAD, and FE parts • GS1-144 was well-tolerated with no notable safety signals • PK was linear with a moderate half-life, supporting q24h or q12h dosing regimens • Dose-dependent LH suppression confirmed PD activity 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 30mg 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 T max 0.5–2.0 hours) 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 hours, with no dose-dependent changes. Dose-dependent LH reductions were observed across 15–120 mg, with consistent effects between 30mg q12h and 60mg 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.

Source: European Journal of Pharmaceutical Sciences

DOI: 10.1016/j.ejps.2026.107443