Daridorexant to Treat Insomnia in Patients With Mild Cognitive Impairment and Mild to Moderate Alzheimer Disease

Inclusion criteria

• 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).
• For a male subject who is not sterilized and is sexually active with a female partner of childbearing potential, no contraceptive methods are needed
• Non inclusion criteria :
• Patients significantly dependent on caregivers
• 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
• History of narcolepsy and/or cataplexy
• History of drug or alcohol abuse or addiction
• 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)
• Treatments interfering with sleep-wake patterns
• Use of hypnotics (benzodiazepines, zolpidem, zopiclone) or drug for pain level 3 (morphine and derivatives)
• Hypersensitivity to the active substance or to any of the excipients listed in the Summary of Product Characteristics (SmPC)
• 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
• 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
• Failure to obtain written informed consent after a reflection period