Safety and Efficacy Study of YZJ-1139 in Insomnia Disorder

A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter, Phase 3 Clinical Study to Evaluate the Efficacy and Safety of YZJ-1139 Tablets in the Treatment of Insomnia Disorder

The main purpose of this study is to assess efficacy and safety of YZJ-1139 in adult subjects with insomnia disorder. Efficacy will be evaluated on objective and subjective sleep parameters.

Inclusion Criteria:

- Subjects who meet all of the following criteria may be enrolled in the study:

1. Aged ≥ 18 to < 65 years.

2. Meet the clinical diagnostic criteria for insomnia disorder as defined in International Classification of Sleep Disorders, 3rd Edition (ICSD-3) criteria.

3. sTSO ≥ 30 min for at least 3 nights per week and/or sWASO ≥ 60 min for at least 3 nights per week within 28 days (4 weeks) prior to screening.

4. During the run-in period or on Day 1 of the treatment period, sTSO ≥ 30 min for at least 3 nights in the last 7 sleep diaries and/or sWASO ≥ 60 min for at least 3 nights out of 7 nights as confirmed by the sleep diary prior to Polysomnography (PSG) monitoring.

5. PSG results for 2 consecutive nights during the run-in period should meet the following conditions:

   • The mean LPS of 2 nights is ≥ 30 min, with the LPS ≥ 20 min for any night;
   • And/or the mean WASO of 2 nights is ≥ 60 min, with neither night < 45 min;
   • The mean SE of 2 nights is ≤ 85%, with the SE ≤ 87.5% for both nights.

6. ISI score ≥ 15 at screening and on Day 1 of the treatment period.

7. Agree to follow the habitual bedtime between 9 p.m. and 1 a.m., wake up between 5 a.m. and 10 a.m. every day, and stay in bed for 6.5 to 9 hours per night during the study.

8. Have a bedtime between 9 p.m. and 1 a.m., wake up between 5 a.m. and 10 a.m., and stay in bed for 6.5 to 9 hours for at least 5 days in the last 7 sleep diaries as confirmed by the sleep diary prior to PSG monitoring during the run-in period or on Day 1 of the treatment period.

9. Female subjects are confirmed to be non-pregnant at screening; both men of reproductive potential and women of childbearing potential should agree to use medically acceptable and effective contraception throughout the study and within 3 months after the end of the study.

10. Understand the study procedures and contents, voluntarily participate in the clinical study and sign the written Informed Consent Form (ICF), have good compliance during participation in the study, and are willing to attend the visits.

Exclusion Criteria:

• Subjects who meet any of the following criteria should be excluded from this study:

  1. Depression: Hamilton Depression Scale (HAMD) score ≥ 18; anxiety: Hamilton Anxiety Scale (HAMA) score ≥ 14.
  2. Suicidal ideation with or without plan at screening or within 6 months prior to screening (score ≥ 3 on item 3 [suicide] of HAMD, or select "Yes" on item 3, 4 or 5 of suicidal ideation subscale of Columbia-Suicide Severity Rating Scale (C-SSRS)), or have any suicidal behavior in the past 10 years (as assessed by the suicidal ideation subscale of C-SSRS).
  3. Apnea-hypopnea index (AHI) and/or periodic limb movement index (PLMI) > 10 times/hour detected by PSG monitoring during the run-in period.
  4. Repeat electrocardiogram (ECG) at screening shows QTcF interval prolongation (QTcF > 450 ms) (the ECG should be repeated 2 more times only if the initial ECG shows QTcF interval > 450 ms).
  5. Have serious endocrine diseases, hematological diseases, cardiovascular and cerebrovascular diseases, gastrointestinal diseases, liver and kidney diseases, autoimmune diseases, impaired respiratory function or other related diseases, or have other medical history that may affect the safety of the subjects or interfere with the study assessments in the opinion of the investigator.
  6. Have insomnia disorder due to other causes such as chronic pain, headache, eczema, neurodermatitis, allergic rhinitis, and serious dermatitis (difficulty sleeping due to physical reasons, difficulty falling asleep due to medical reasons).
  7. Previous history of nervous system disorders such as epilepsy, schizophrenia, bipolar mental disorder, neurodevelopmental retardation, and cognitive disorder, or previous history of other mental illness that may affect the safety of the subjects or interfere with the study assessments in the opinion of the investigator.
  8. Previous history of sleep-related respiratory disorders including obstructive sleep apnea (with or without continuous positive airway pressure (CPAP) therapy), periodic limb movement disorder, restless legs syndrome, circadian rhythm sleep disturbances, narcolepsy or other sleep disorders: subjects with restless legs syndrome which is diagnosed by relevant diagnostic and treatment guidelines should be excluded.
  9. Have previous complex sleep behaviors, such as sleep driving, sleep eating, and sleep phone calls.
  10. Plan to undergo surgery during the study.
  11. Have received any hypnotics, antidepressants, antipsychotic drugs, anticholinergics, memory-enhancing drugs, antihistamines, centrally acting analgesics, centrally acting muscle relaxants, central nervous system stimulants, cytochrome P450 3A (CYP3A) inducers, CYP3A inhibitors, traditional Chinese medicines and traditional Chinese medicinal products with sleep-improving effects, or any other therapies for insomnia disorder within 1 week prior to the run-in period or within 5 half-lives of the investigational product, whichever is longer.
  12. History of drug taking or addiction, which is known through questioning.
  13. Have any lifestyle that interferes with the study process or may interfere with sleep: for example, there will be travels across 3 or more time zones (mainland China is considered as 1 time zone) within the next 2 weeks or during the study period, or there will be shift work (night and daytime shift).
  14. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 2 × the upper limit of normal (ULN), or Creatinine (Cr) > 1.5 × ULN.
  15. Hyperthyroidism.
  16. History of alcohol abuse (defined as regular daily alcohol consumption exceeding the following criteria: approximately 720 mL of beer, or 240 mL of wine, or 60 mL of liquor) within the past 2 years.
  17. History of drug abuse within the past 2 years, or positive urine drug screening for any indicator.
  18. Regular daily consumption of excessive tea and coffee drinks (defined as consumption of > 4 cups of caffeinated beverages or > 400 mg of caffeine per day), or daily habituation to drinking caffeinated beverages beyond 18:00.
  19. Have nocturia increased caused by urinary tract infection, urinary tract injury or prostatic disorder.
  20. Have positive infectious disease screening for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCVAb) and human immunodeficiency virus (HIV) antibody at screening.
  21. Unable to avoid vaccination within 1 month prior to screening or during the first treatment phase.
  22. Have participated in clinical studies of other drugs within the past 1 month or 5 half-lives (whichever is longer), or plan to participate in other studies simultaneously during participation in this study.
  23. Pregnant or lactating women.
  24. History of allergy to the investigational product or its components.
  25. Have prior participation in clinical studies of YZJ-1139 Tablets.
  26. Have other conditions that make the subject unsuitable for participation in the clinical study in the opinion of the investigator.