Overview
The primary purpose of this study is to assess the efficacy and safety of 50 mg daridorexant in adult and elderly chinese patients with insomnia disorder.
Efficacy will be evaluated on objective and subjective sleep parameters .
Eligibility
Inclusion Criteria:
- Signed informed consent prior to any study-mandated procedure.
- Male or female aged ≥ 18 years old, ≤75 years old.
- Insomnia disorder according to diagnostic and statistical Manual of Mental Disorder,
Fifth Edition (DSM-5®) criteria, as follows:
3.1 The predominant complaint is dissatisfaction with sleep quantity or quality, associated with one (or more) of the following symptoms:
- Difficulty initiating sleep
- Difficulty maintaining sleep, characterized by frequent awakenings or problems returning to sleep after awakenings.
- Early-morning awakening with inability to return to sleep. 3.2 The sleep disturbance causes clinically significant distress or impairment in social, occupational, educational, academic, behavioral, or other important areas of functioning.
3.3 The sleep difficulty occurs despite adequate opportunity for sleep. 3.4 The
insomnia is not better explained by another sleep-wake disorder (e.g., narcolepsy, a
breathing-related sleep disorder, a circadian rhythm sleep-wake disorder, a
parasomnia).
3.5 The insomnia is not attributable to the physiological effects of a substance (e.
g., a drug of abuse, a medication) 3.6 Coexisting mental disorders and medical
conditions do not adequately explain the predominant complaint of insomnia.
3.7 Self-reported history of all the following on at least 3 nights per week and for
at least 3 months prior to Visit 1: 3.7.1 ≥30 min to fall asleep, and 3.7.2 Wake time
during sleep ≥ 30 min, and 3.7.3 Subjective Total Sleep Time (sTST)≤6.5 h
4. Insomnia Severity Index© score≥15
5. Ability to communicate well with the investigator, to understand the study
requirements and independently complete the study, as judged by the investigator, to
be alert and oriented to person, place, time, and situation.
6. Meeting all the following sleep parameters on at least 3 nights out of 7 nights on the
eDiary completed at home between Visit 3 and Visit 4:
6.1 ≥ 30 min to fall asleep, and 6.2 Wake time during sleep ≥ 30 min, and 6.3 sTST of
≤ 6.5 h
7. Usual bedtime between 20:30 and 00:30 as reported on sleep diary completed between
Visit 3 and Visit 4.
8. Regular time in bed between 6 and 9 h as reported on sleep diary completed between
Visit 3 and Visit 4.
9. Meeting all the following sleep parameters on the 2 PSG nights at Visit 4:
9.1 Mean Latency to Persistent Sleep (LPS) ≥ 20 min (with neither of the two nights <
15 min), and 9.2 Mean Wake After Sleep Onset (WASO) ≥ 30 min (with neither of the two
nights < 20 min), and 9.3 Mean Total Sleep Time (TST) < 420 min
10. For women of childbearing potential, the following are required:
- Negative serum pregnancy test (Visit 1).
- Negative urine pregnancy test (Visit 3, Visit 5).
11. Female and male subjects agree to use the contraception scheme as required by the
protocol from Screening visit up to at least 30 days after last D B study treatment
intake, and have no plans to become pregnant, planned parenthood or sperm/egg donation
plans, unless they have been sterilization surgically (with surgery at least 1 month
before dosing), or female are postmenopausal (female subjects with natural menopause
≥12 months, ≥ 50 years old, can be considered postmenopausal after exclusion of
pregnancy and other disorders that may cause amenorrhea; If age <50 years by follicle
stimulating hormone level confirmed).
Exclusion Criteria:
1. Chronic obstructive pulmonary disease, or any lifetime history of sleep-related
breathing disorderlike sleep apnea.
2. Cognitive behavioral therapy (CBT) for any indication is allowed only if the CBT
started at least 1 month prior to Visit 4 and the subject agrees to continue this CBT
throughout the study.
3. Self-reported usual daytime napping ≥ 1 h per day, and ≥ 3 days per week.
4. Acute or unstable psychiatric conditions (including but not restricted to anxiety
disorder, major depression, bipolar disorder, schizophrenia, obsessive compulsive
disorder, or depression) that are diagnosed by the Mini International Neuropsychiatric
Interview© or that require pharmacological treatment for these disorders. N.B.:
subjects with a history of major depressive disorder currently without any symptoms
and not requiring treatment are eligible.
5. Mini Mental State Examination© score < 25 in subjects ≥ 50 years.
6. Shift work within 2 weeks prior to the screening visit, or planned shift work during
the study.
7. Travel across ≥ 3 time zones within 2 weeks prior to the screening visit, or planned
travel across ≥ 3 time zones during the study.
8. Treatment with central nervous system-active drugs, including over-the- counter
medication and herbal medicines, are prohibited by this protocol within 5 half-lives
of the respective drug (or 2 weeks, whichever is longer) prior to Visit 1, and until
24 h after the end of treatment (the end of the run-out period).
9. Diagnosis of alcohol or substance use disorder within 2 years prior to the screening
visit or inability to refrain from drinking alcohol for at least 3 consecutive days.
10. Heavy tobacco use (at least one pack of cigarettes a day or inability to refrain from
smoking during the night).
11. Caffeine consumption ≥ 600 mg per day or any caffeine consumption after 4 pm
12. Use of traditional Chinese medicine as prophylaxis or treatment of sleep disturbance
within 4 weeks prior to Visit 1 and during the treatment phase.
13. Treatment with another investigational drug within 3 months prior to Visit 1, previous
treatment with daridorexant or other orexin receptor antagonists (i.e. lemborexant,
YZJ-1139) or previous randomization in any trial involving daridorexant
14. Known hypersensitivity or contraindication to drugs of the same class as the study
treatment or to any excipients of the study drug formulation.
15. Not able or willing to stop treatment with moderate or strong cytochrome P450 (CYP)3A4
inhibitors, or treatment with moderate or strong CYP3A4 inducers, within at least 1
week prior to Visit 3, until the end of treatment (the end of the run-out period).
16. Not able or willing to stop consumption of grapefruit, Seville (bitter) oranges or
juices from those fruits within at least 1 week prior to Visit 3, and until the end of
treatment (the end of placebo run-out period).
17. A prolonged QTc interval calculated using Fridericia's formula (QTcF) interval (QTcF
greater than 450 ms). If the QTcF is greater than 450 ms on the first single 12-lead
ECG, 2 additional 12-lead ECGs will be performed (at least after 30 min) and the mean
of the 3 QTcF values will be calculated. (QTcF alculation formula seen in 11.5
Appendix)
18. Periodic limb movement disorder with arousal index (PLMAI)
≥ 15/h (assessed on the 1st PSG night), restless legs syndrome, circadian rhythm
disorder, rapid eye movement (REM) behavior disorder, or narcolepsy.
19. Apnea/hypopnea index ≥ 15/h according to American Academy of Sleep Medicine criteria
or event associated with blood oxygen saturation level by pulse oximetry (SpO2) < 80%,
as assessed on the 1st PSG night
20. A history of moderate to severe hepatic impairment (eg, Child-Pugh Class B or C).
(details in 11.6 Appendix)
21. Sleep diary completed less than 70% between Visit 3 to Visit 4, or at least 3 days out
of the 7 days immediately preceding the first PSG of visit 4.
22. Subjects who took placebo tablets less than 80% of days in from Visit 3 to Visit 4.
Criteria assessed at Visit 1, Visit 2, Visit 3, Visit 4 and Visit 5
23. Any of the following conditions related to suicidality:
- Any suicidal ideation with intent, with or without a plan, at screening, i.e.,
answering "Yes" to questions 4 or 5 on the suicidal ideation section of the
lifetime (Visit 1) and visit (Visit 2, Visit 3, Visit 4, Visit 5) version of the
Columbia Suicide Severity Rating Scale© (C-SSRS©).
- History of suicide attempt on the suicidal behavioral section of the lifetime
version of the C-SSRS© (Visit 1).
24. Coronavirus Disease 2019 (COVID-19) positive subjects, supported by Antigen test or
Nucleic acid detection.
25. For female subjects: pregnant, lactating or planning to become pregnant during
projected duration of the study.
26. Positive urine drug test or presence of alcohol in exhaled breath as detected by
breathalyzer test.
27. Unstable medical condition, significant medical disorder or acute illness, ECG,
hematology or biochemistry test, thyroid function or coagulation test results within 1
month prior to the screening visit, which, in the opinion of the investigator, could
affect the subject's safety or interfere with the study assessments.