Insomnia Disorder
Conditions
Keywords
Clinical trial, insomnia disorder, open-label, long-term, phase 3
Brief summary
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
DRUGHS-10506
HS-10506 tablet
Sponsors
Jiangsu Hansoh Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
1. Participants must be 18 to 65 years of age (inclusive 18, not inclusive 65); 2. Participants are required to voluntarily sign the informed consent form; 3. Body mass index (BMI): BMI (weight/height2 \[kg/m2\]) must be in the range of 18 to 35 kg/m2 (inclusive); 4. 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; 5. For new Participants: Participants must meet Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-5) criteria for insomnia disorder; 6. For new Participants: Participants must have Insomnia Severity Index (ISI) scores≥15 at screening; 7. 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
1. 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; 2. 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; 3. 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; 4. 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; 5. Has a history of drug dependency or abuse within the past 1 year or showed positive in urine drug test at screening; 6. Has a history of alcohol abuse within the past 1 year or can't obey the rules of alcohol restriction; 7. Has a history of smoking≥10 cigars daily within the past 3 months or can't obey the rules of cigar restriction; 8. Has a history of caffeine consumption≥600 mg per day or can't obey the rules of caffeine restriction; 9. Has been working across 3 or more time zones or shift work within 2 weeks prior to screening; 10. Has taken more than 3 naps per week for\>1 hour each time within the past 2 weeks prior to screening; 11. 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. 12. 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; 13. 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; 14. For Participants completed Study 301: Previously participated in any clinical trial other than HS-10506-301 within 3 months prior to screening; 15. 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; 16. 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; 17. For new Participants: Previously use of HS-10506; 18. For new Participants: Previously participated in any clinical trial within 3 months prior to screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of serious adverse events (SAE) | From date of signing the informed consent until the date of the end-of-study visit or early withdrawal, assessed up to 13 months | An SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participants and/or may require medical or surgical intervention to prevent one of the outcomes listed above. |
| Incidence and severity of adverse events of special interest (AESI) | From date of signing the informed consent until the date of the end-of-study visit or early withdrawal, assessed up to 13 months | An AESI (serious or non-serious) is any medical event specific to the investigational product or clinical trial. |
| Incidence and severity of adverse events (AE) | From date of signing the informed consent until the date of the end-of-study visit or early withdrawal, assessed up to 13 months | An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in subjective total sleep time (sTST) under the treatment of HS-10506 | Baseline, every 4 weeks during Open-Label Treatment Period (up to 12 months) | sTST: the total sleep time reported by the participant in sleep diary |
| Number of Participants With Clinically Significant Change in hematology | Baseline, Week 12, Week 24, Week 36, Week 48 | Hematology tests will include hemoglobin, hematocrit, red blood cell count, platelets, white blood cell count, count and absolute lymphocytes, neutrophils, basophils, eosinophils, monocytes. Any clinically significant change in hematological values will be determined at the investigator's discretion |
| Number of Participants With Clinically Significant Change in clinical chemistry | Baseline, Week 12, Week 24, Week 36, Week 48 | Clinical chemistry tests will include total and direct bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, albumin, total protein, creatinine, glucose, hemoglobin A1c (HbA1c), creatinine kinase. Any clinically significant change in clinical chemistry values will be determined at the investigator's discretion. |
| Number of Participants With Clinically Significant Change in urinalysis | Baseline, Week 12, Week 24, Week 36, Week 48 | Urinalysis will include glucose, ketones, urine red blood cells, urine white blood cells. Any clinically significant change in urinalysis values will be determined at the investigator's discretion. |
| Withdrawal symptoms by Physician Withdrawal Checklist (PWC-20) | The day after the last administration and at least 7 days after discontinuation of the medication | The PWC-20 is a 20-item questionnaire and the score of each item ranges from 0-3 (0=not present, 1=mild, 2=moderate, 3=severe) with higher scores indicating greater severity of withdrawal symptoms |
| Rebound insomnia by subjective sleep onset latency (sSOL) during the follow-up period | Baseline, Follow-up Period (7-9 days) | — |
| Rebound insomnia by subjective wake after sleep onset (sWASO) during the follow-up period | Baseline, Follow-up Period (7-9 days) | — |
| Change from baseline in subjective sleep onset latency (sSOL) under the treatment of HS-10506 | Baseline, every 4 weeks during Open-Label Treatment Period (up to 12 months) | sSOL: estimated minutes from the time that the participant attempted to sleep until sleep onset as recorded in sleep diary |
| Rebound insomnia by subjective total sleep time (sTST) during the follow-up period | Baseline, Follow-up Period (7-9 days) | — |
| Change from baseline in subjective sleep efficiency (sSE) under the treatment of HS-10506 | Baseline, every 4 weeks during Open-Label Treatment Period (up to 12 months) | sSE: the ratio of subjective total sleep time (sTST) to subjective time in bed |
| Change from baseline in subjective wake after sleep onset (sWASO) under the treatment of HS-10506 | Baseline, every 4 weeks during Open-Label Treatment Period (up to 12 months) | sWASO: estimated minutes of wake at night from initial sleep onset to the time when the participant stopped trying to sleep as recorded in sleep diary |
Contacts
CONTACTYuping Wang, Principal Investigator
Outcome results
None listed