Daridorexant to Treat Insomnia in Patients With Mild Cognitive Impairment and Mild to Moderate Alzheimer Disease (DARIDOR-ALZ)

University Hospital Center (CHU)

Status and phase

Enrolling

Phase 4

Conditions

Alzheimer Disease

Insomnia Disorder

Sleep

Treatments

Other: Biomarker assay

Behavioral: Neuropsychological assessment

Procedure: Polysomnography

Procedure: 24-hour Ambulatory Blood Pressure Monitoring (ABPM

Behavioral: Questionnaires on sleep and behavioural problems

Procedure: Actimetrics

Drug: Placebo

Drug: Daridorexant 50 mg

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT05924425

RECHMPL22_0529

Details and patient eligibility

About

DARIDOR-ALZ is a phase IV clinical trial designed to evaluate both the efficacy and safety of daridorexant, a selective dual orexin receptor antagonist that blocks the actions of the orexin neuropeptides at both orexin-1 and orexin-2 receptors, in selected populations of MCI and mild-to-moderate AD patients with insomnia complaints.

Full description

This Phase IV clinical trial is a monocentric, randomized, double-blind, placebo-controlled, 2 way-crossover study (with two periods of one month separated by a washout period range from 5 to 12 days).The study population includes MCI and mild-to-moderate AD patients aged between 60 and 85 years old, with insomnia complaints.

A single-night baseline polysomnography recording will be performed from 11 pm to 7 am at the Montpellier Sleep Unit. After a baseline PSG that assessed TST < 6 hours and WASO > 1 hour, treatment will be assigned using an interactive response technology system.

A randomization list will be generated and will remain confidential until the database is locked. Participants, investigators, and site personnel will be unaware of treatment allocation during the two crossover periods. Patients will be randomized (1:1) to receive daridorexant 50 mg or placebo, without titration, every evening within 30 minutes of going to bed during both treatment periods (Treatment Period A and B) of one-month duration each. Each treatment period will be followed by a one-week (range 5-12 days) washout period at home.

A ten-month open-label (OL) study with daridorexant 50 mg will be proposed to all participants after completing the second treatment period. Based on the experience with another DORA study in patients with mild-to-moderate probable Alzheimer's disease, the investigators would need to recruit 62 patients (including drop-outs).

Enrollment

62 estimated patients

Sex

All

Ages

60 to 85 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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 and sleep diary was below 6 hours, on at least 3 nights per week and for at least 1 month before screening, and
- Insomnia Severity Scale ISI© score ≥ 15
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 biomarker for CSF Aβ42 and neuronal injury (hippocampal and/or temporal atrophy by MRI))
MMSE from 12 to 26
Clinical Dementia Rating CDR from 0.5 to 2
Possible of CNS drugs if stable dose for at least 3 months: anticholinesterase drugs (rivastigmine, donepezil, galantamine) or memantine
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 depression or suicidal ideation/attempt or other psychiatric conditions
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
Psychotropic drugs: antidepressants (SSRI (e.g. fluoxetine, sertraline, paroxetine...), SNRI (e.g. venlafaxine, duloxetine)), neuroleptics (e.g. clozapine, olanzapine, aripiprazole...), and hypnotics (benzodiazepines, zolpidem, zopiclone) or drug for pain (level 2 (e.g. codeine, tramadol), and 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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Crossover Assignment

Masking

Quadruple Blind

62 participants in 2 patient groups, including a placebo group

Daridorexant 50 mg

Experimental group

Description:

Patients will receive daridorexant 50 mg during one month (Period A or Period B). Daridorexant is an orally administered dual orexin type 1 and type 2 (OX1 and OX2) receptor antagonist (DORA) being developed for the treatment of insomnia.

Treatment: