Safety, pharmacokinetics and pharmacodynamics of HRS‐7535, a novel oral small molecule glucagon‐like peptide‐1 receptor agonist, in healthy participants: A phase 1, randomized, double‐blind, placebo‐controlled, single‐ and multiple‐ascending dose, and food effect trial

• DOI: 10.1111/dom.15383
• Publication Date: 2023-12-15T17:47:15Z
• Authors: Jingying Wu; Renpeng Zhou; Qian Zhang; Qin Zhang; Huiling Qin; Zi Ye; Yimei Xu; Sheng Feng; Chang Shu; Yu Shen; Yang Fan; Quanren Wang; Yijun Du; Wei Hu
• Keywords: Tolerability; Pharmacodynamics; Crossover study

Abstract Aim To assess the safety, tolerability, pharmacokinetics (PKs) and pharmacodynamics of HRS‐7535, a novel glucagon‐like peptide‐1 receptor agonist (GLP‐1RA), in healthy participants. Materials Methods This phase 1 trial consisted single‐ascending dose (SAD), food effect (FE) multiple‐ascending (MAD) parts. In SAD part, participants were randomized (6:2) to receive HRS‐7535 (at doses 15, 60 120 mg; administered orally once daily) or placebo. FE (8:2) single 90‐mg placebo, both fed fasted states. MAD (18:6) daily (120 mg [30/60/90/120‐mg titration scheme]) placebo for 28 days. The primary endpoints safety tolerability. Results Nausea vomiting most frequently reported AEs across all three median T max was 5.98‐5.99 hours geometric mean t 1/2 5.28‐9.08 dosing range. 5.98‐10.98 6.48‐8.42 on day HRS‐7535. PKs approximately dose‐proportional. On 29 (percentage) reduction body weight from baseline 4.38 kg (6.63%) who received compared with 0.8 (1.18%) those Conclusions exhibited tolerability profile consistent other GLP‐1RAs showed suitable once‐daily dosing. These findings support further clinical development type 2 diabetes.