MedPath

Safety and Efficacy Study of YZJ-1139 in Insomnia Disorder

Phase 3
Recruiting
Conditions
Insomnia Disorder
Interventions
Drug: Placebo
Drug: YZJ-1139 20mg
Drug: YZJ-1139 40mg
Registration Number
NCT05525637
Lead Sponsor
Shanghai Haiyan Pharmaceutical Technology Co., Ltd.
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
1041
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.

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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.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlacebo-
YZJ-1139 20mgYZJ-1139 20mg-
YZJ-1139 40mgYZJ-1139 40mg-
Primary Outcome Measures
NameTimeMethod
Change from baseline in the subjective sleep efficiency (sSE) after 14 days of treatmentfrom baseline to week 2

Subjective Sleep efficiency variation assessed by the sleep diary questionnaire at 14 days of treatment from baseline. A positive change from baseline indicates an increase in the subjective Sleep efficiency. A negative change from baseline indicates a decrease in subjective Sleep efficiency

Change from baseline in the sleep efficiency (SE) after 14 days of treatmentfrom baseline to day 14

Sleep efficiency variation assessed by polysomnography at 14 days of treatment from baseline. A positive change from baseline indicates an increase in the Sleep efficiency. A negative change from baseline indicates a decrease in Sleep efficiency

Secondary Outcome Measures
NameTimeMethod
Changes from baseline in the Subjective wake after sleep onset (sWASO) after 14 days of treatment for subjects entering the second treatment phaseBaseline, week 1, week 2

sWASO are self-reported sleep outcome measured by subject diary data, collected daily and analyzed at appropriate intervals.

Latency to persistent sleep (LPS) after 2 and 14 days of treatmentBaseline, Day1/Day2, Day13/Day14

LPS assessed by polysomnography at 2 and 14 days of treatment from baseline. A positive change from baseline indicates an increase in the Sleep efficiency. A negative change from baseline indicates a decrease in Sleep efficiency

Wake after sleep onset (WASO) after 2 and 14 days of treatmentBaseline, Day1/Day2, Day13/Day14

WASO assessed by polysomnography at 2 and 14 days of treatment from baseline. A positive change from baseline indicates an increase in the Sleep efficiency. A negative change from baseline indicates a decrease in Sleep efficiency

Total sleep time (TST) after 2 and 14 days of treatmentBaseline, Day1/Day2, Day13/Day14

TST assessed by polysomnography at 2 and 14 days of treatment from baseline. A positive change from baseline indicates an increase in the Sleep efficiency. A negative change from baseline indicates a decrease in Sleep efficiency

Changes from baseline in the Subjective time to sleep onset (sTSO) after 14 days of treatment for subjects entering the second treatment phaseBaseline, week 1, week 2

sTSO are self-reported sleep outcome measured by subject diary data, collected daily and analyzed at appropriate intervals.

Changes from baseline in the SE after 2 days of treatmentBaseline, Day1/Day2

SE assessed by polysomnography at 2 days of treatment from baseline. A positive change from baseline indicates an increase in the Sleep efficiency. A negative change from baseline indicates a decrease in Sleep efficiency

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 treatmentBaseline, Day1/Day2, Day13/Day14

Sleep structure assessed by polysomnography at 2 and 14 days of treatment from baseline.

Changes from baseline in the sTSO after 30, 90 and 180 days of treatment for subjects entering the second treatment phaseBaseline, Day 30, Day 90, and Day 180

sTSO are self-reported sleep outcome measured by subject diary data, collected daily and analyzed at appropriate intervals.

Changes from baseline in the sNAW after 30, 90 and 180 days of treatment for subjects entering the second treatment phaseBaseline, Day 30, Day 90, and Day 180

sNAW are self-reported sleep outcome measured by subject diary data, collected daily and analyzed at appropriate intervals.

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 treatmentDay 30, Day 90, and Day 180

The PGI-I was a self-report assessment of participant perception of the effects of a medication on their sleep. The PGI-I had 3 items related to study medication effects (a) helped/worsened sleep, (b) decreased/increased time to fall asleep, (c) increased/decreased total sleep time, and 1 item related to perceived appropriateness of study medication strength. The first 3 items were answered on a 3-point scale (1=positive medication effect, 2=neutral medication effect, 3=negative medication effect) and the last item on a different 3 point scale (medication: 1=too strong, 2=just right, 3=too weak).

Changes from baseline in the Subjective total sleep time (sTST) after 14 days of treatment for subjects entering the second treatment phaseBaseline, week 1, week 2

sTST are self-reported sleep outcome measured by subject diary data, collected daily and analyzed at appropriate intervals.

Change from baseline in the subjective sleep efficiency (sSE) after 7 days of treatmentBaseline, week 1

sSE is self-reported sleep outcome measured by subject diary data, collected daily and analyzed at appropriate intervals.

Changes from baseline in the Subjective number of awakenings (sNAW) after 14 days of treatment for subjects entering the second treatment phaseBaseline, week 1, week 2

sNAW are self-reported sleep outcome measured by subject diary data, collected daily and analyzed at appropriate intervals.

Change from baseline in the mean subjective sleep quality score after 7 and 14 days of treatment for subjectsBaseline, Week 1, Week 2

Subjective sleep quality score is a self-report assessment of participant perception of the effects of a medication on their sleep. Higher score indicated severe insomnia problem.

Percentage of Participants on each scale of Global Impression of Insomnia (PGI-I) each Item at 14 days of treatmentDay 14

The PGI-I was a self-report assessment of participant perception of the effects of a medication on their sleep. The PGI-I had 3 items related to study medication effects (a) helped/worsened sleep, (b) decreased/increased time to fall asleep, (c) increased/decreased total sleep time, and 1 item related to perceived appropriateness of study medication strength. The first 3 items were answered on a 3-point scale (1=positive medication effect, 2=neutral medication effect, 3=negative medication effect) and the last item on a different 3 point scale (medication: 1=too strong, 2=just right, 3=too weak)

Changes from baseline in the sSE after 30, 90 and 180 days of treatment for subjects entering the second treatment phaseBaseline, Day 30, Day 90, and Day 180

sSE are self-reported sleep outcome measured by subject diary data, collected daily and analyzed at appropriate intervals.

Changes from baseline in the sTST after 30, 90 and 180 days of treatment for subjects entering the second treatment phaseBaseline, Day 30, Day 90, and Day 180

sTST are self-reported sleep outcome measured by subject diary data, collected daily and analyzed at appropriate intervals.

Change from baseline in the Insomnia Severity Index (ISI) score after 30, 90 and 180 days of treatment for subjects entering the second treatment phaseBaseline, Day 30, Day 90, and Day 180

ISI is a self-report questionnaire assessing the nature, severity, and impact of insomnia. Higher score indicated severe insomnia problem.

Changes from baseline in the sWASO after 30, 90 and 180 days of treatment for subjects entering the second treatment phaseBaseline, Day 30, Day 90, and Day 180

sWASO are self-reported sleep outcome measured by subject diary data, collected daily and analyzed at appropriate intervals.

Change from baseline in the mean subjective sleep quality score after 30, 90 and 180 days of treatment for subjects entering the second treatment phaseBaseline, Day 30, Day 90, and Day 180

Subjective sleep quality score is a self-report assessment of participant perception of the effects of a medication on their sleep. Higher score indicated severe insomnia problem.

Trial Locations

Locations (88)

WuXi People's Hospital

🇨🇳

Wuxi, China

HeNan University Of Science &Technology

🇨🇳

Luoyang, China

NingBo KangNing Hospital

🇨🇳

Ningbo, China

The affilated hospital of qingdao university

🇨🇳

Qingdao, China

Affiliated Hospital Of Jiangnan University

🇨🇳

Wuxi, China

ZiGong First People's Hospital

🇨🇳

Zigong, China

Beijing Tiantan Hospital, Capital Medical University

🇨🇳

Beijing, China

Beijing Hui Long Guan Hospital, Capital Medical University

🇨🇳

Beijing, China

Beijing Chao-Yang Hospital, Capital Medical University

🇨🇳

Beijing, China

Beijing Tsinghua Changgung Hospital

🇨🇳

Beijing, China

China-Japan Friendship Hospital

🇨🇳

Beijing, China

Peking University First Hospital

🇨🇳

Beijing, China

The First affiliated hospital of bengbu medical college

🇨🇳

Bengbu, China

Peking University People's Hospital

🇨🇳

Beijing, China

Xuanwu Hospital Capital Medical University

🇨🇳

Beijing, China

Binzhou Medical University Hospital

🇨🇳

Binzhou, China

The First Bethune Hospital Of Jilin University

🇨🇳

Changchun, China

The First Hospital of ChangSha

🇨🇳

Changsha, China

The Second XiangYa Hospital Of Central University

🇨🇳

Changsha, China

The Secong People's Hospital Of HuNan Province

🇨🇳

Changsha, China

ChengDu Second People's Hospital

🇨🇳

Chengdu, China

Xiangya Hospital Central South University

🇨🇳

Changsha, China

The Fourth People's Hospital Of ChengDu

🇨🇳

Chengdu, China

ChongQing Eleventh People's Hospital

🇨🇳

ChongQing, China

Army Medical Center of PLA

🇨🇳

Chongqing, China

ChongQing Mental Health Center

🇨🇳

ChongQing, China

ChongQing University Three Gorges Hospital

🇨🇳

ChongQing, China

ChongQing Traditional Chinese Medical Hospital

🇨🇳

ChongQing, China

People's Hospital Of DeYang City

🇨🇳

Deyang, China

Nanfang Hospital Southern Medical University

🇨🇳

Guangzhou, China

The First Affiliated Hospital Of FuJan Medical University

🇨🇳

Fuzhou, China

Guangdong Provincial People's Hospital

🇨🇳

Guangzhou, China

The 2nd Affiliated Hospital Of Harbin Medical University

🇨🇳

Ha'erbin, China

The First Affiliated Hospital of Jinan University

🇨🇳

Guangzhou, China

The Affiliated Hospital Of GuiZhou Medical University

🇨🇳

Guiyang, China

Sir Run Run Shaw hospital

🇨🇳

Hangzhou, China

HanDan Central Hospital

🇨🇳

HanDan, China

The Second Hospital Of AnHui Medical University

🇨🇳

Hefei, China

Affiliated HangZhou First People's Hospital

🇨🇳

Hangzhou, China

Chaohu hospital of anhui medical university

🇨🇳

Hefei, China

The Secong People's Hospital Of HeFei

🇨🇳

Hefei, China

Affiliated NanHua Hospital,University Of South China

🇨🇳

Hengyang, China

JiangMen Central Hospital

🇨🇳

Jiangmen, China

ShanDong Provincial QianFoShan Hospital

🇨🇳

Jinan, China

Jingjiang People's Hospital

🇨🇳

Jingjiang, China

Shandong Daizhuang Hospital

🇨🇳

Jining, China

Jiujiang University Affiliated Hospital

🇨🇳

Jiujiang, China

LiaoCheng People's Hospital

🇨🇳

Liaocheng, China

First People's Hospital of Yunnan Province

🇨🇳

Kunming, China

The Second Affiliated Hospital Of NanChang University

🇨🇳

Nanchang, China

The First Affiliated Hospital Of NanChang University

🇨🇳

Nanchang, China

The Affiliated Hospital Of Southwest Medical University

🇨🇳

Luzhou, China

JiangXi Provincial People's Hospital

🇨🇳

Nanchang, China

NanTong First People's Hospital

🇨🇳

Nantong, China

NingBo Medical Center LiHuiLi Hospital

🇨🇳

Ningbo, China

QingDao Center Medical Group

🇨🇳

Qingdao, China

QingDao Municipal Hospital

🇨🇳

Qingdao, China

The 2nd Affiliated Hospital Of FuJan Medical University

🇨🇳

Quanzhou, China

Affiliated ZhongShan Hospital,University Of FuDan

🇨🇳

Shanghai, China

HuaShan Hospital Fudan University

🇨🇳

Shanghai, China

ShengJing Hospital Of China Medical University

🇨🇳

Shenyang, China

ShangHai University Of Traditional Chinese Medical Shuguang Hospital

🇨🇳

Shanghai, China

The First Hospital of Hebei Medical University

🇨🇳

Shijiazhuang, China

ShenZhen People's Hospital

🇨🇳

Shenzhen, China

The Third Hospital of Hebei Medical University

🇨🇳

Shijiazhuang, China

Jilin Neuropsychiatric Hospital

🇨🇳

Siping, China

SuZhou GuangJi Hospital

🇨🇳

SuZhou, China

The Second Affiliated Hospital of Soochow University

🇨🇳

Suzhou, China

The First People's Hospital Of KunShan

🇨🇳

Suzhou, China

Peking University BinHai Hospital

🇨🇳

Tianjin, China

Tianjin Huanhu Hospital

🇨🇳

Tianjin, China

Tianjin Mental Health Center

🇨🇳

Tianjin, China

The Center Hospital of WuHan

🇨🇳

Wuhan, China

Unidn Hospital TongJi Medical College HuaZhong University Of Science And Technology

🇨🇳

Wuhan, China

Wuhan Mental Health Centre

🇨🇳

Wuhan, China

Air Force Medical University

🇨🇳

Xi'an, China

XianYang Hospital OF Yan'an University

🇨🇳

Xianyang, China

HeNan Mental Hospital

🇨🇳

Xinxiang, China

The Affiliated Hospital Of XuZhou Medical University

🇨🇳

Xuzhou, China

XuZhou Central Hospital

🇨🇳

Xuzhou, China

HeNan Provincial People's Hospital

🇨🇳

Zhengzhou, China

ZhenZhou Central Hospital

🇨🇳

Zhengzhou, China

The First Affiliated Hospital Of ZhenZhou University

🇨🇳

Zhengzhou, China

ZhenJiang Mental Health Center

🇨🇳

Zhenjiang, China

ZhuMaDian Second People's Hospital

🇨🇳

Zhumadian, China

First Hospital Of ShanXi Medical University

🇨🇳

Taiyuan, China

Zhongda Hospital Southeast Unveristy

🇨🇳

Nanjing, China

NanJing Drum Tower Hospital

🇨🇳

Nanjing, China

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