Daridorexant to treat insomnia in patients with mild cognitive impairment and mild to moderate Alzheimer disease.

Prior treatment

• Use of hypnotics (benzodiazepines, zolpidem, zopiclone) or drug for pain level 3 (morphine and derivatives)
• Forbidden and restricted concomitant medications: • Concomitant CNS-depressant medicinal products • CYP3A4 inhibitors • CYP3A4 inducers
• Participation in another clinical trial or administration of an investigational product

Other illness

• History of diagnosed and characterized psychiatric disorders (DSM-5), cured or stabilized (with or without the same treatment for at least 3 months) and excluding any current characterized psychiatric disorder (DSM-5), the diagnosis of which is established by a psychiatrist trained in geriatric psychiatry
• Moderate and severe liver failure
• PSG baseline evidence of significant/severe sleep-related breathing disorder (defined as >30 apnea/hypopnea episodes per hour)
• Hypersensitivity to the active substance or to any of the excipients listed in the Summary of Product Characteristics (SmPC)
• Failure to obtain written informed consent after a reflection period
• History of narcolepsy and/or cataplexy
• History of drug or alcohol abuse or addiction

Other

• Patients significantly dependent on caregivers
• Treatments interfering with sleep-wake patterns
• Protected population according to articles of the French Public Health Code (e.g. patients under law protection, prisoners, pregnant, parturient or lactating women, and patients under guardianship/curatorship)
• Subjects not covered by public health insurance
• Institutionalized patients
• Analphabetism or subjects unable to read or/and write
• Patients unable to perform the neuropsychological tests
• Patients unable to complete the study instruments (sleep diary)
• Planned longer stay outside the region that prevents compliance with the visit schedule
• Patients who cannot be followed up for at least 2 months

• Age [60-85] years old.
• Outpatients
• Pre-screening: • Complaints of dissatisfaction with sleep quantity or quality, despite adequate opportunity for sleep, at least 3 nights per week and for at least 3 months, and • Total sleep time causes clinically significant distress or impairment in daytime functioning, and • Total sleep time estimated by interview was below 6 hours, on at least 3 nights per week and for at least 1 month before screening
• Baseline PSG (at randomization) assessed TST < 6 hours and WASO > 1 hour
• Diagnosis of MCI and AD patients at an early stage according to the NIA diagnosis criteria (core clinical criteria for MCI, positive CSF Aβ42 and/or positive plasma biomarker, and neuronal injury (hippocampal and/or temporal atrophy by MRI))
• MMSE from 12 to 26
• Clinical Dementia Rating CDR from 0.5 to 2
• Use of CNS-active medications is permitted provided the dose has been stable for at least 3 months, including: anticholinesterase drugs (rivastigmine, donepezil, galantamine) or memantine, antidepressants SSRI (e.g. fluoxetine, sertraline, paroxetine…), SNRI (e.g. venlafaxine, duloxetine), neuroleptics (e.g. clozapine, olanzapine, aripiprazole...) or drug for pain level 2 (codeine, tramadol)