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, 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.
