Safety, Efficacy and Pharmacokinetics of HS-10506 in the Insomnia Patients: A Randomized, Double-Blind, Placebo-Controlled, Phase 1b/2 Study
YuPing Wang1, Zhaoyang Huang1, Qiaorong Xu2, Jian Wang3, Haihang Yu4, Qinying Ma5, Hanqiao Wang6, Daomin Zhu7, Shiyou Tang8, Xia Liu9, Xianxiang Zeng10, Bin Zhang11, Bo Zhou12, Shize Li13, Ran Liu14, Rui Zhang14, Lu Yu14, Xiaoqing Zhang14
1Xuanwu Hospital, Capital Medical University, 2Xianyang Hospital of Yan'an University, 3Chengdu Second People's Hospital, 4The Affiliated Kangning Hospital of Ningbo University, 5The First Hospital of Hebei Medical University, 6The Third Hospital of Hebei Medical University, 7Anhui Mental Health Center, 8Chongqing Three Gorges Central Hospital, 9Shandong Daizhuang Hospital, 10Hunan Second Provincial People’s Hospital (Hunan Brain Hospital), 11Nanfang Hospital of Southern Medical University, 12Sichuan Provincial People's Hospital, 13Zhengzhou Central Hospital Affiliated to Zhengzhou University, 14Shanghai Hansoh BioMedical Co., Ltd.
Objective:
To evaluate the safety, efficacy, and pharmacokinetics of HS-10506 in adults with insomnia.
Background:
HS-10506, a highly selective orexin-2 receptor antagonist, has shown potential sleep-promoting effects in preclinical studies and was well tolerated in a phase 1a trial (NCT05953506).
Design/Methods:
This is a randomized, double-blind, placebo-controlled phase 1b/2 trial (NCT06279286). In phase 1b, insomnia patients were randomized 3:1 to HS-10506 or placebo at multiple ascending doses of 10, 20, 40 and 80 mg (n=8 per cohort) to evaluate safety and pharmacokinetics. In phase 2, patients were equally randomized to receive 20 mg, 40 mg, 60 mg HS-10506, or placebo once-nightly for 28 days. The primary endpoint was the change from baseline in polysomnography-measured latency to persistent sleep (LPS) on Days 13 and 14 (D13/14).
Results:
A total of 32 (phase 1b) and 238 (phase 2) patients received treatment. HS-10506 demonstrated a favorable safety profile across all doses. In phase 2, treatment-emergent adverse events occurring in >=5% of patients of any group were somnolence and urinary tract infection. LPS changes from baseline to D13/14 versus placebo were -13.7 (95% CI, -21.0 to -6.4; P<0.001), -16.6 (95% CI, -23.8 to -9.3; P<0.001), and -18.8 (95% CI, -26.1 to -11.6; P<0.001) minutes for the 20 mg, 40 mg, and 60 mg HS-10506 groups, respectively, demonstrating clinically meaningful reductions. HS-10506 also showed sustained and consistent improvements over placebo in both objective and subjective sleep parameters. In phase 1b, HS-10506 was rapidly absorbed and eliminated post-single dose without significant accumulation after multiple dosing.
Conclusions:
HS-10506 was well-tolerated and demonstrated sustained efficacy in improving sleep onset and maintenance in insomnia patients. Its favorable pharmacokinetic profile facilitated prompt sleep initiation with minimal residual daytime effect. These findings support advancing HS-10506 to a phase 3 study.
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