A Study to Evaluate the Safety of HS-10506 in Chinese Patients With Insomnia Disorder

Official title

A Multicenter, Open-label, Phase 3 Study to Evaluate the Short-term and Long-term Safety of HS-10506 in Chinese Adult Patients With Insomnia Disorder

Overview

The primary purpose of this open-label phase Ⅲ study is to evaluate the safety of HS-10506 on the incidence and severity of adverse events (AE), serious adverse events (SAE), adverse events of special interest (AESI) in Chinese adult participants with insomnia disorder.

Detailed description

The study will comprise 4 periods : a Screening Period, a Run-in Period, an Open-Label Treatment Period during which participants will be treated for 4, 24, 36, or 48 consecutive weeks and a minimum 7-day Follow-up Period before an End of Study (EOS) Visit. The total study duration for each participant on this study is 2-13 months.

Interventions

• Drug HS-10506
  HS-10506 tablet

Primary outcome measures

• Incidence and severity of adverse events (AE) [Time frame: From date of signing the informed consent until the date of the end-of-study visit or early withdrawal, assessed up to 13 months]
• Incidence and severity of serious adverse events (SAE) [Time frame: From date of signing the informed consent until the date of the end-of-study visit or early withdrawal, assessed up to 13 months]
• Incidence and severity of adverse events of special interest (AESI) [Time frame: From date of signing the informed consent until the date of the end-of-study visit or early withdrawal, assessed up to 13 months]

Secondary outcome measures (11)

• Number of Participants With Clinically Significant Change in hematology [Time frame: Baseline, Week 12, Week 24, Week 36, Week 48]
• Number of Participants With Clinically Significant Change in clinical chemistry [Time frame: Baseline, Week 12, Week 24, Week 36, Week 48]
• Number of Participants With Clinically Significant Change in urinalysis [Time frame: Baseline, Week 12, Week 24, Week 36, Week 48]
• Withdrawal symptoms by Physician Withdrawal Checklist (PWC-20) [Time frame: The day after the last administration and at least 7 days after discontinuation of the medication]
• Rebound insomnia by subjective sleep onset latency (sSOL) during the follow-up period [Time frame: Baseline, Follow-up Period (7-9 days)]
• Rebound insomnia by subjective wake after sleep onset (sWASO) during the follow-up period [Time frame: Baseline, Follow-up Period (7-9 days)]
• Rebound insomnia by subjective total sleep time (sTST) during the follow-up period [Time frame: Baseline, Follow-up Period (7-9 days)]
• Change from baseline in subjective sleep onset latency (sSOL) under the treatment of HS-10506 [Time frame: Baseline, every 4 weeks during Open-Label Treatment Period (up to 12 months)]
• Change from baseline in subjective sleep efficiency (sSE) under the treatment of HS-10506 [Time frame: Baseline, every 4 weeks during Open-Label Treatment Period (up to 12 months)]
• Change from baseline in subjective wake after sleep onset (sWASO) under the treatment of HS-10506 [Time frame: Baseline, every 4 weeks during Open-Label Treatment Period (up to 12 months)]
• Change from baseline in subjective total sleep time (sTST) under the treatment of HS-10506 [Time frame: Baseline, every 4 weeks during Open-Label Treatment Period (up to 12 months)]

Eligibility criteria

Inclusion criteria

• Participants must be 18 to 65 years of age (inclusive 18, not inclusive 65);
• Participants are required to voluntarily sign the informed consent form;
• Body mass index (BMI): BMI (weight/height2 \[kg/m2\]) must be in the range of 18 to 35 kg/m2 (inclusive);
• For Participants completed Study 301: Participants have completed the Study 301, can potentially benefit from extended treatment with HS-10506 and have no major safety risks according to the investigator's clinical judgment;
• For new Participants: Participants must meet Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-5) criteria for insomnia disorder;
• For new Participants: Participants must have Insomnia Severity Index (ISI) scores≥15 at screening;
• For new Participants: Participants must have an sSOL≥30 minutes, sWASO≥30 minutes, and sTST<6.5 hours for at least three nights every week within one month prior to screening; and sSOL≥30 minutes, sWASO≥30 minutes, and sTST<6.5 hours for at least 3 nights from sleep diary in the last 7 consecutive days before the first dose in the open-label treatment period;

Exclusion criteria

• Has received systemic hypnotherapy, cognitive behavioral therapy (CBT), or other non-pharmacological treatments for insomnia in last 4 weeks or have plans during the study;
• Has a risk of suicide according to the Columbia Suicide Severity Rating Scale (C-SSRS), or has a high risk of suicide at the discretion of the investigator;
• Has used any medication that may affect the pharmacokinetics of HS-10506 or GLP-1R-related single/multi-target drugs within the past 2 weeks or 5 half-lives of the medication;
• Has used any medication that may affect sleep-wake function, or any other prohibited central nervous system active medications within 1 week or 5 half-lives of the medication;
• Has a history of drug dependency or abuse within the past 1 year or showed positive in urine drug test at screening;
• Has a history of alcohol abuse within the past 1 year or can't obey the rules of alcohol restriction;
• Has a history of smoking≥10 cigars daily within the past 3 months or can't obey the rules of cigar restriction;
• Has a history of caffeine consumption≥600 mg per day or can't obey the rules of caffeine restriction;
• Has been working across 3 or more time zones or shift work within 2 weeks prior to screening;
• Has taken more than 3 naps per week for>1 hour each time within the past 2 weeks prior to screening;
• Has any circumstances or conditions, which, in the opinion of the investigator, may affect the subject's full participation in the study or compliance with the protocol.
• For Participants completed Study 301: Has been diagnosed with a sleep-wake disorders or sleep-related breathing disorders other than insomnia disorder during Study 301, such as restless legs syndrome, periodic limb movement disorder, circadian rhythm disorder, narcolepsy, rapid eye movement sleep phase (REM) behavioral disorders, and obstructive sleep apnea;
• For Participants completed Study 301: Has been diagnosed with neurodevelopmental retardation, cognitive impairment, epilepsy, schizophrenia, bipolar disorder, hyperthyroidism, cancer, severe cardio-cerebrovascular diseases or respiratory diseases; or current chronic pain that affects sleep, nocturia resulting in frequent need to get out of bed to use the bathroom during the night; or clinically significant and/or unstable neurological, psychiatric, respiratory, cardiovascular, digestive, immunologic, urologic, endocrine diseases during Study 301; or other systemic diseases that are inappropriate for the study;
• For Participants completed Study 301: Previously participated in any clinical trial other than HS-10506-301 within 3 months prior to screening;
• For new Participants: Has history of/current sleep-wake disorders or sleep-related breathing disorders other than insomnia disorder, such as restless legs syndrome, periodic limb movement disorder, circadian rhythm disorder, narcolepsy, rapid eye movement sleep phase (REM) behavioral disorders, and obstructive sleep apnea;
• For new Participants: Has history of/current neurodevelopmental retardation, cognitive impairment, epilepsy, schizophrenia, bipolar disorder, hyperthyroidism, cancer, severe cardio-cerebrovascular diseases or respiratory diseases; or current chronic pain that affects sleep, nocturia resulting in frequent need to get out of bed to use the bathroom during the night; or clinically significant and/or unstable neurological, psychiatric, respiratory, cardiovascular, digestive, immunologic, urologic, endocrine diseases within the past 3 months prior to screening; or other systemic diseases that are inappropriate for the study;
• For new Participants: Previously use of HS-10506;
• For new Participants: Previously participated in any clinical trial within 3 months prior to screening.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07677384 · HS-10506-303

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗