On September 21-24, the 37th Congress of the European College of Neuropsychopharmacology (ECNP) was held in Milan, Italy. The latest clinical research data on Hansoh Pharma's Class 1 innovative drug HS-10506, a novel, high-affinity selective orexin-2 receptor (OX2R) antagonist, were presented in the form of a poster at the conference, with insomnia as its potential indication. 

The annual ECNP Congress is Europe’s premier scientific meeting for disease-oriented brain research, annually attracting around 6,000 psychiatrists, neuroscientists，neurologists and psychologists from around the world. The recently published clinical trial results of  HS-10506 was safe and well-tolerated following a single oral dose up to 60 mg with a favorable PK profile and a desired pharmacodynamic (somnolence) effect. Overall, the data support continued clinical development of HS-10506 for insomnia. 

Study Profile

A Randomized, Double-blinded, Placebo-controlled, Single Ascending Dose Study of HS-10506 in Healthy Subjects

Format:Poster Presentation

Abstract:#P4044

First author：Shanghai Mental Health Center, Shanghai Jiao Tong University School of ♔Medicine, Shanghai, China, Yan Li

Last author：Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China,🏅𓃲 Huafang Li

DATE: September 21-24, 2024

 

Introduction and Objective:

HS-10506, a novel, high affinity selective OX2R antagonist which targets the orexin system with sleep-promoting effects in preclinical studies, is under investigation for insomnia treatment. The objective of this study is to investigate the safety, tolerability, and pharmacokinetic characteristics of HS-10506 after single oral administration in Chinese healthy subjects. 

Methods:

This was a randomized, double-blind, placebo-controlled trial. Fifty-two healthy subjects in 5 dose-groups (2.5 mg, 7.5 mg, 20 mg, 40 mg, and 60 mg) received HS-10506 or placebo once in the morning. Safety assessments included adverse events (AEs), vital signs, electrocardiograms, clinical laboratory assessments, and suicidality evaluation per Columbia Suicide Severity Rating Scale (C-SSRS). HS-10506 plasma concentrations were determined using validated liquid chromatography-tandem mass spectrometry with a lower limit of quantitation of 0.2 ng/mL. The dose proportionality of HS-10506 was assessed by log-transformed AUC and Cmax using a power model. 

Results:

No deaths, serious adverse events (AEs) or early withdrawal events due to safety issue were reported in this study. Overall, 33 of 39 subjects (84.6%) who received HS-10506 and 5 of 13 placebo-treated subjects (38.5%) had at least one adverse event. The most common AEs (>2 cases) were sleepiness (76.9% for HS-10506 versus 38.5% for placebo), somnolence (71.8% for HS-10506 versus 23.1% for placebo) and dizziness (10.3% for HS-10506 versus 0 for placebo).).No clinically significant abnormalities were observed in the vital signs (heart rate, blood pressure), clinical laboratory data and C-SSRS evaluation. The incidences of somnolence were reported as 0% (0/6), 50.0% (3/6), 88.9% (8/9), 88.9% (8/9) and 100.0% (9/9) in the 2.5, 7.5, 20, 40 and 60 mg HS-10506 dose groups, respectively, and 38.5% (5/13) in the placebo group. Except for somnolence and drowsiness, all other AEs were mild in severity. In general, somnolence was reported shortly after drug administration (7.5-60 mg), which was of mild to severe intensity, and showed a dose-related trend. HS-10506 was rapidly absorbed with a median Tmax ranging from 0.5 to 1.0 hour and a terminal half-life of ~2-5 hours. Systemic exposure to HS-10506 increased with dose in a less than dose-proportional manner. 

Conclusion:

HS-10506 was safe and well-tolerated following a single oral dose up to 60 mg with a favorable PK profile and a desired pharmacodynamic (somnolence) effect. Overall, the data support continued clinical development of HS-10506 for insomnia.