Safety and Efficacy Study of YZJ-1139 in Insomnia Disorder

Insomnia Disorder Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05525637
• Other study ID #: YZJ-1139-3-01
• Status: Recruiting
• Phase: Phase 3
• Start date: December 17, 2021
• Est. completion date: December 2024

Study information

• Verified date: April 2024
• Source: Shanghai Haiyan Pharmaceutical Technology Co., Ltd.
• Contact: Fang Han
• Phone: 010-88324206
• Email: hanfang1[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1041
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Insomnia Disorder
• Sleep Initiation and Maintenance Disorders

Intervention

Drug:
• YZJ-1139 20mg
YZJ-1139 20mg tablets, once daily in the evening
• YZJ-1139 40mg
YZJ-1139 40mg tablets, once daily in the evening
• Placebo
Match placebo tablets, once daily in the evening

Locations

Country	Name	City	State
China	Beijing Chao-Yang Hospital, Capital Medical University	Beijing
China	Beijing Hui Long Guan Hospital, Capital Medical University	Beijing
China	Beijing Tiantan Hospital, Capital Medical University	Beijing
China	Beijing Tsinghua Changgung Hospital	Beijing
China	China-Japan Friendship Hospital	Beijing
China	Peking University First Hospital	Beijing
China	Peking University People's Hospital	Beijing
China	Xuanwu Hospital Capital Medical University	Beijing
China	The First affiliated hospital of bengbu medical college	Bengbu
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	Xiangya Hospital Central South University	Changsha
China	ChengDu Second People's Hospital	Chengdu
China	The Fourth People's Hospital Of ChengDu	Chengdu
China	Army Medical Center of PLA	Chongqing
China	ChongQing Eleventh People's Hospital	ChongQing
China	ChongQing Mental Health Center	ChongQing
China	ChongQing Traditional Chinese Medical Hospital	ChongQing
China	ChongQing University Three Gorges Hospital	ChongQing
China	People's Hospital Of DeYang City	Deyang
China	The First Affiliated Hospital Of FuJan Medical University	Fuzhou
China	Guangdong Provincial People's Hospital	Guangzhou
China	Nanfang Hospital Southern Medical University	Guangzhou
China	The First Affiliated Hospital of Jinan University	Guangzhou
China	The Affiliated Hospital Of GuiZhou Medical University	Guiyang
China	The 2nd Affiliated Hospital Of Harbin Medical University	Ha'erbin
China	HanDan Central Hospital	HanDan
China	Affiliated HangZhou First People's Hospital	Hangzhou
China	Sir Run Run Shaw hospital	Hangzhou
China	Chaohu hospital of anhui medical university	Hefei
China	The Second 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	First People's Hospital of Yunnan Province	Kunming
China	LiaoCheng People's Hospital	Liaocheng
China	HeNan University Of Science &Technology	Luoyang
China	The Affiliated Hospital Of Southwest Medical University	Luzhou
China	JiangXi Provincial People's Hospital	Nanchang
China	The First Affiliated Hospital Of NanChang University	Nanchang
China	The Second Affiliated Hospital Of NanChang University	Nanchang
China	NanJing Drum Tower Hospital	Nanjing
China	Zhongda Hospital Southeast Unveristy	Nanjing
China	NanTong First People's Hospital	Nantong
China	NingBo KangNing Hospital	Ningbo
China	NingBo Medical Center LiHuiLi Hospital	Ningbo
China	QingDao Center Medical Group	Qingdao
China	QingDao Municipal Hospital	Qingdao
China	The affilated hospital of qingdao university	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	ShangHai University Of Traditional Chinese Medical Shuguang Hospital	Shanghai
China	ShengJing Hospital Of China Medical University	Shenyang
China	ShenZhen People's Hospital	Shenzhen
China	The First Hospital of Hebei Medical University	Shijiazhuang
China	The Third Hospital of Hebei Medical University	Shijiazhuang
China	Jilin Neuropsychiatric Hospital	Siping
China	SuZhou GuangJi Hospital	SuZhou
China	The First People's Hospital Of KunShan	Suzhou
China	The Second Affiliated Hospital of Soochow University	Suzhou
China	First Hospital Of ShanXi Medical University	Taiyuan
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	Affiliated Hospital Of Jiangnan University	Wuxi
China	WuXi People's Hospital	Wuxi
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	The First Affiliated Hospital Of ZhenZhou University	Zhengzhou
China	ZhenZhou Central Hospital	Zhengzhou
China	ZhenJiang Mental Health Center	Zhenjiang
China	ZhuMaDian Second People's Hospital	Zhumadian
China	ZiGong First People's Hospital	Zigong

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Haiyan Pharmaceutical Technology Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in the subjective sleep efficiency (sSE) after 14 days of treatment	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	from baseline to week 2
Primary	Change from baseline in the sleep efficiency (SE) after 14 days of treatment	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	from baseline to day 14
Secondary	Change from baseline in the subjective sleep efficiency (sSE) after 7 days of treatment	sSE is self-reported sleep outcome measured by subject diary data, collected daily and analyzed at appropriate intervals.	Baseline, week 1
Secondary	Changes from baseline in the Subjective time to sleep onset (sTSO) after 14 days of treatment for subjects entering the second treatment phase	sTSO are self-reported sleep outcome measured by subject diary data, collected daily and analyzed at appropriate intervals.	Baseline, week 1, week 2
Secondary	Changes from baseline in the Subjective wake after sleep onset (sWASO) after 14 days of treatment for subjects entering the second treatment phase	sWASO are self-reported sleep outcome measured by subject diary data, collected daily and analyzed at appropriate intervals.	Baseline, week 1, week 2
Secondary	Changes from baseline in the Subjective total sleep time (sTST) after 14 days of treatment for subjects entering the second treatment phase	sTST are self-reported sleep outcome measured by subject diary data, collected daily and analyzed at appropriate intervals.	Baseline, week 1, week 2
Secondary	Changes from baseline in the Subjective number of awakenings (sNAW) after 14 days of treatment for subjects entering the second treatment phase	sNAW are self-reported sleep outcome measured by subject diary data, collected daily and analyzed at appropriate intervals.	Baseline, week 1, week 2
Secondary	Changes from baseline in the SE after 2 days of treatment	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	Baseline, Day1/Day2
Secondary	Latency to persistent sleep (LPS) after 2 and 14 days of treatment	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	Baseline, Day1/Day2, Day13/Day14
Secondary	Wake after sleep onset (WASO) after 2 and 14 days of treatment	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	Baseline, Day1/Day2, Day13/Day14
Secondary	Total sleep time (TST) after 2 and 14 days of treatment	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	Baseline, Day1/Day2, Day13/Day14
Secondary	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	Sleep structure assessed by polysomnography at 2 and 14 days of treatment from baseline.	Baseline, Day1/Day2, Day13/Day14
Secondary	Change from baseline in the mean subjective sleep quality score after 7 and 14 days of treatment for subjects	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.	Baseline, Week 1, Week 2
Secondary	Percentage of Participants on each scale of Global Impression of Insomnia (PGI-I) each Item at 14 days of treatment	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)	Day 14
Secondary	Changes from baseline in the sSE after 30, 90 and 180 days of treatment for subjects entering the second treatment phase	sSE are self-reported sleep outcome measured by subject diary data, collected daily and analyzed at appropriate intervals.	Baseline, Day 30, Day 90, and Day 180
Secondary	Changes from baseline in the sTSO after 30, 90 and 180 days of treatment for subjects entering the second treatment phase	sTSO are self-reported sleep outcome measured by subject diary data, collected daily and analyzed at appropriate intervals.	Baseline, Day 30, Day 90, and Day 180
Secondary	Changes from baseline in the sWASO after 30, 90 and 180 days of treatment for subjects entering the second treatment phase	sWASO are self-reported sleep outcome measured by subject diary data, collected daily and analyzed at appropriate intervals.	Baseline, Day 30, Day 90, and Day 180
Secondary	Changes from baseline in the sTST after 30, 90 and 180 days of treatment for subjects entering the second treatment phase	sTST are self-reported sleep outcome measured by subject diary data, collected daily and analyzed at appropriate intervals.	Baseline, Day 30, Day 90, and Day 180
Secondary	Changes from baseline in the sNAW after 30, 90 and 180 days of treatment for subjects entering the second treatment phase	sNAW are self-reported sleep outcome measured by subject diary data, collected daily and analyzed at appropriate intervals.	Baseline, Day 30, Day 90, and Day 180
Secondary	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	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.	Baseline, Day 30, Day 90, and Day 180
Secondary	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	ISI is a self-report questionnaire assessing the nature, severity, and impact of insomnia. Higher score indicated severe insomnia problem.	Baseline, Day 30, Day 90, and Day 180
Secondary	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	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).	Day 30, Day 90, and Day 180