Clinical trial NCT05525637: Safety and Efficacy Study of YZJ-1139 in Insomnia Disorder
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Insomnia Disorder
Lead sponsor: Shanghai Haiyan Pharmaceutical Technology Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-09-01
Enrollment: 1041
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change from baseline in the subjective sleep efficiency (sSE) after 14 days of treatment
timeFrame: from baseline to week 2
measure: Change from baseline in the sleep efficiency (SE) after 14 days of treatment
timeFrame: from baseline to day 14
Secondary outcomes:
measure: Change from baseline in the subjective sleep efficiency (sSE) after 7 days of treatment
timeFrame: Baseline, week 1
measure: Changes from baseline in the Subjective time to sleep onset (sTSO) after 14 days of treatment for subjects entering the second treatment phase
timeFrame: Baseline, week 1, week 2
measure: Changes from baseline in the Subjective wake after sleep onset (sWASO) after 14 days of treatment for subjects entering the second treatment phase
timeFrame: Baseline, week 1, week 2
measure: Changes from baseline in the Subjective total sleep time (sTST) after 14 days of treatment for subjects entering the second treatment phase
timeFrame: Baseline, week 1, week 2
measure: Changes from baseline in the Subjective number of awakenings (sNAW) after 14 days of treatment for subjects entering the second treatment phase
timeFrame: Baseline, week 1, week 2
measure: Changes from baseline in the SE after 2 days of treatment
timeFrame: Baseline, Day1/Day2
measure: Latency to persistent sleep (LPS) after 2 and 14 days of treatment
timeFrame: Baseline, Day1/Day2, Day13/Day14
measure: Wake after sleep onset (WASO) after 2 and 14 days of treatment
timeFrame: Baseline, Day1/Day2, Day13/Day14
measure: Total sleep time (TST) after 2 and 14 days of treatment
timeFrame: Baseline, Day1/Day2, Day13/Day14
measure: Sleep structure (wakefulness, N1, N2, N3, rapid eye movement sleep [REM], non-rapid eye movement sleep [NREM], REM latency, number of awakenings [NAW], arousal index for REM and NREM) after 2 and 14 days of treatment
timeFrame: Baseline, Day1/Day2, Day13/Day14
measure: Change from baseline in the mean subjective sleep quality score after 7 and 14 days of treatment for subjects
timeFrame: Baseline, Week 1, Week 2
measure: Percentage of Participants on each scale of Global Impression of Insomnia (PGI-I) each Item at 14 days of treatment
timeFrame: Day 14
measure: Changes from baseline in the sSE after 30, 90 and 180 days of treatment for subjects entering the second treatment phase
timeFrame: Baseline, Day 30, Day 90, and Day 180
measure: Changes from baseline in the sTSO after 30, 90 and 180 days of treatment for subjects entering the second treatment phase
timeFrame: Baseline, Day 30, Day 90, and Day 180
measure: Changes from baseline in the sWASO after 30, 90 and 180 days of treatment for subjects entering the second treatment phase
timeFrame: Baseline, Day 30, Day 90, and Day 180
measure: Changes from baseline in the sTST after 30, 90 and 180 days of treatment for subjects entering the second treatment phase
timeFrame: Baseline, Day 30, Day 90, and Day 180
measure: Changes from baseline in the sNAW after 30, 90 and 180 days of treatment for subjects entering the second treatment phase
timeFrame: Baseline, Day 30, Day 90, and Day 180
measure: Change from baseline in the mean subjective sleep quality score after 30, 90 and 180 days of treatment for subjects entering the second treatment phase
timeFrame: Baseline, Day 30, Day 90, and Day 180
measure: Change from baseline in the Insomnia Severity Index (ISI) score after 30, 90 and 180 days of treatment for subjects entering the second treatment phase
timeFrame: Baseline, Day 30, Day 90, and Day 180
measure: Percentage of Participants who enter the second treatment phase on each scale of Patient Global Impressions - ImprovementGlobal Impression of Insomnia (PGI-I) each Item at 30, 90 and 180 days of treatment
timeFrame: Day 30, Day 90, and Day 180
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Chao-Yang Hospital, Capital Medical University
city: Beijing
country: China
facility: Beijing Hui Long Guan Hospital, Capital Medical University
city: Beijing
country: China
facility: Beijing Tiantan Hospital, Capital Medical University
city: Beijing
country: China
facility: Beijing Tsinghua Changgung Hospital
city: Beijing
country: China
facility: China-Japan Friendship Hospital
city: Beijing
country: China
facility: Peking University First Hospital
city: Beijing
country: China
facility: Peking University People's Hospital
city: Beijing
country: China
facility: Xuanwu Hospital Capital Medical University
city: Bengbu
country: China
facility: The First affiliated hospital of bengbu medical college
city: Binzhou
country: China
facility: Binzhou Medical University Hospital
city: Changchun
country: China
facility: The First Bethune Hospital Of Jilin University
city: Changsha
country: China
facility: The First Hospital of ChangSha
city: Changsha
country: China
facility: The Second XiangYa Hospital Of Central University
city: Changsha
country: China
facility: The Secong People's Hospital Of HuNan Province
city: Changsha
country: China
facility: Xiangya Hospital Central South University
city: Chengdu
country: China
facility: ChengDu Second People's Hospital
city: Chengdu
country: China
facility: The Fourth People's Hospital Of ChengDu
city: Chongqing
country: China
facility: Army Medical Center of PLA
city: ChongQing
country: China
facility: ChongQing Eleventh People's Hospital
city: ChongQing
country: China
facility: ChongQing Mental Health Center
city: ChongQing
country: China
facility: ChongQing Traditional Chinese Medical Hospital
city: ChongQing
country: China
facility: ChongQing University Three Gorges Hospital
city: Deyang
country: China
facility: People's Hospital Of DeYang City
city: Fuzhou
country: China
facility: The First Affiliated Hospital Of FuJan Medical University
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
city: Guangzhou
country: China
facility: Nanfang Hospital Southern Medical University
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Jinan University
city: Guiyang
country: China
facility: The Affiliated Hospital Of GuiZhou Medical University
city: Ha'erbin
country: China
facility: The 2nd Affiliated Hospital Of Harbin Medical University
city: HanDan
country: China
facility: HanDan Central Hospital
city: Hangzhou
country: China
facility: Affiliated HangZhou First People's Hospital
city: Hangzhou
country: China
facility: Sir Run Run Shaw hospital
city: Hefei
country: China
facility: Chaohu hospital of anhui medical university
city: Hefei
country: China
facility: The Second Hospital Of AnHui Medical University
city: Hefei
country: China
facility: The Secong People's Hospital Of HeFei
city: Hengyang
country: China
facility: Affiliated NanHua Hospital,University Of South China
city: Jiangmen
country: China
facility: JiangMen Central Hospital
city: Jinan
country: China
facility: ShanDong Provincial QianFoShan Hospital
city: Jingjiang
country: China
facility: Jingjiang People's Hospital
city: Jining
country: China
facility: Shandong Daizhuang Hospital
city: Jiujiang
country: China
facility: Jiujiang University Affiliated Hospital
city: Kunming
country: China
facility: First People's Hospital of Yunnan Province
city: Liaocheng
country: China
facility: LiaoCheng People's Hospital
city: Luoyang
country: China
facility: HeNan University Of Science &Technology
city: Luzhou
country: China
facility: The Affiliated Hospital Of Southwest Medical University
city: Nanchang
country: China
facility: JiangXi Provincial People's Hospital
city: Nanchang
country: China
facility: The First Affiliated Hospital Of NanChang University
city: Nanchang
country: China
facility: The Second Affiliated Hospital Of NanChang University
city: Nanjing
country: China
facility: NanJing Drum Tower Hospital
city: Nanjing
country: China
facility: Zhongda Hospital Southeast Unveristy
city: Nantong
country: China
facility: NanTong First People's Hospital
city: Ningbo
country: China
facility: NingBo KangNing Hospital
city: Ningbo
country: China
facility: NingBo Medical Center LiHuiLi Hospital
city: Qingdao
country: China
facility: QingDao Center Medical Group
city: Qingdao
country: China
facility: QingDao Municipal Hospital
city: Qingdao
country: China
facility: The affilated hospital of qingdao university
city: Quanzhou
country: China
facility: The 2nd Affiliated Hospital Of FuJan Medical University
city: Shanghai
country: China
facility: Affiliated ZhongShan Hospital,University Of FuDan
city: Shanghai
country: China
facility: HuaShan Hospital Fudan University
city: Shanghai
country: China
facility: ShangHai University Of Traditional Chinese Medical Shuguang Hospital
city: Shenyang
country: China
facility: ShengJing Hospital Of China Medical University
city: Shenzhen
country: China
facility: ShenZhen People's Hospital
city: Shijiazhuang
country: China
facility: The First Hospital of Hebei Medical University
city: Shijiazhuang
country: China
facility: The Third Hospital of Hebei Medical University
city: Siping
country: China
facility: Jilin Neuropsychiatric Hospital
city: SuZhou
country: China
facility: SuZhou GuangJi Hospital
city: Suzhou
country: China
facility: The First People's Hospital Of KunShan
city: Suzhou
country: China
facility: The Second Affiliated Hospital of Soochow University
city: Taiyuan
country: China
facility: First Hospital Of ShanXi Medical University
city: Tianjin
country: China
facility: Peking University BinHai Hospital
city: Tianjin
country: China
facility: Tianjin Huanhu Hospital
city: Tianjin
country: China
facility: Tianjin Mental Health Center
city: Wuhan
country: China
facility: The Center Hospital of WuHan
city: Wuhan
country: China
facility: Unidn Hospital TongJi Medical College HuaZhong University Of Science And Technology
city: Wuhan
country: China
facility: Wuhan Mental Health Centre
city: Wuxi
country: China
facility: Affiliated Hospital Of Jiangnan University
city: Wuxi
country: China
facility: WuXi People's Hospital
city: Xi'an
country: China
facility: Air Force Medical University
city: Xianyang
country: China
facility: XianYang Hospital OF Yan'an University
city: Xinxiang
country: China
facility: HeNan Mental Hospital
city: Xuzhou
country: China
facility: The Affiliated Hospital Of XuZhou Medical University
city: Xuzhou
country: China
facility: XuZhou Central Hospital
city: Zhengzhou
country: China
facility: HeNan Provincial People's Hospital
city: Zhengzhou
country: China
facility: The First Affiliated Hospital Of ZhenZhou University
city: Zhengzhou
country: China
facility: ZhenZhou Central Hospital
city: Zhenjiang
country: China
facility: ZhenJiang Mental Health Center
city: Zhumadian
country: China
facility: ZhuMaDian Second People's Hospital
city: Zigong
country: China
facility: ZiGong First People's Hospital
Study officials:
References: