A Study of the Effect of Daridorexant on Nighttime Body Posture, the Noise Level Required to Wake up, and the Ability to Remember Words Previously Presented

Study Overview
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Brief Summary
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A Study of the Effect of Daridorexant on Nighttime Body Posture, the Noise Level Required to Wake up, and the Ability to Remember Words Previously Presented

Official Title
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Single-center, Randomized, Double-blind, Single-dose, 3-way Crossover Study to Compare the Effects of Daridorexant and Placebo on Postural Stability, the Auditory Awakening Threshold, and Cognitive Function in the Middle-of-the-night Following Evening Administration to Healthy Adult and Elderly Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Daridorexant 25 mg
* Drug: Daridorexant 50 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent in a language understandable to the subject prior to any study-mandated procedure. Male and female subjects aged 18 years or older at Screening (18 subjects must be 65 years or older). Woman of childbearing potential (WoCBP) who has a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day 1 pre-dose. She must agree to use consistently and correctly (from Screening, during the entire study, and for at least 5-7 days after last study treatment administration) an acceptable method of contraception with a failure rate of less than 1% per year, be sexually inactive, or have a vasectomized partner. If a hormonal contraceptive is used, it must be initiated 1 month before first treatment administration. Woman of non-childbearing potential, i.e., postmenopausal (defined as 12 consecutive months with no menses without an alternative medical cause, confirmed by a follicle-stimulating hormone [FSH] test), with previous bilateral salpingectomy, bilateral-oophorectomy or hysterectomy, or with premature ovarian failure (confirmed by a specialist), XY genotype, Turner syndrome, or uterine agenesis. Body mass index (BMI) of 18.0 to 35.0 kg/m2 (inclusive) at Screening. Ability to communicate well with the investigator, in a language understandable to the subject, and to understand and comply with the study requirements. Exclusion Criteria: Known hypersensitivity to daridorexant, or treatments of the same class, or any of its excipients. Any known factor or disease (e.g., unstable medical condition, significant medical disorder, or acute illness) that might interfere with subject's safety, study conduct, or interpretation of the results, such as History of narcolepsy. Shift work within 2 weeks prior to Screening, or planned shift work during the study. Travel across 3 or more time zones within 1 week prior to Screening, or planned travel across 3 or more time zones during the study. Previous (i.e., within 2 weeks prior to first study treatment administration) and ongoing treatment with any prescribed central nervous system (CNS)-active medications, and/or diuretics that would affect nighttime rest, and/or moderate to strong cytochromes P450(CYP)3A4 inhibitors or inducers.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Daridorexant 25 mg<br>Subjects will receive a daridorexant 25 mg tablet for oral administration. | Drug: Daridorexant 25 mg<br>* A single-dose of daridorexant 25 mg will be administered in the evening 30 minutes prior to bedtime.<br>* Other names: Quviviq;|
| Experimental: Daridorexant 50 mg<br>Subjects will receive a daridorexant 50 mg tablet for oral administration. | Drug: Daridorexant 50 mg<br>* A single-dose of daridorexant 50 mg will be administered in the evening 30 minutes prior to bedtime.<br>* Other names: Quviviq;|
| Placebo Comparator: Placebo<br>Subjects will receive a daridorexant-matching placebo tablet for oral administration. | Drug: Placebo<br>* A single-dose of placebo matching daridorexant will be administered in the evening 30 minutes prior to bedtime.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment difference in postural stability (daridorexant and placebo) | Postural stability in the MOTN (at 4 h post-dose) evaluated by body sway. Body sway will be assessed approximately 5 min after awakening, with the subject standing comfortably, with eyes closed, using a body sway meter (string attached to the waist). Body movements over 2 min are integrated and expressed as mm sway. | Approximately 4 hours post-dose on Day 2 of the treatment period (daridorexant and placebo). Total duration: 12 hours. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment difference in auditory awakening threshold (daridorexant and placebo) | The auditory awakening threshold will be assessed at 4 h post dose by applying a 1000 Hz tone, starting at a noise level of 35 dB, increasing in steps of 5 dB until either the subject is awake, or the maximum noise level (100 dB) is reached. The tone will be delivered via a calibrated loudspeaker for 3 s with a 15 s interval between the different noise levels. The subjects must confirm awakening by verbally saying I'm awake or similar response, e.g., waving a hand. If a subject does not respond after receiving the initial 100 dB tone, additional 100 dB stimuli will be applied in 15 s intervals for up to 2 min. The outcome measure is the noise level (dB) at which subjects indicate that they are awake. If a subject remains asleep, he/she will be physically awakened by a technician. If a subject will not awaken to any of the tones presented, the maximum 100 dB tone will be recorded as the auditory awakening threshold. | Approximately 4 hours post-dose on Day 2 of the treatment period (daridorexant and placebo). Total duration: 12 hours. | 
| Treatment difference in the timed up and go test (daridorexant and placebo) |  | Approximately 4 hours post-dose on Day 2 of the treatment period (daridorexant and placebo). Total duration: 12 hours. | 
| Treatment difference in the visual verbal learning test (daridorexant and placebo) |  | Approximately 4 hours post-dose on Day 2 of the treatment period (daridorexant and placebo). Total duration: 12 hours. |