Study evaluating the efficacy and safety of daridorexant in patients with major depressive disorder and insomnia.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacio Institut D'Investigacio Biomedica De Bellvitge IDIBELL

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Decision date (initial)

2026-05-04

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy

To evaluate the efficacy of Daridorexant in improving insomnia assessed with the ISI in MDD patients at 3 months.

Secondary objectives 5

1. To evaluate the efficacy of Daridorexant compared to placebo in improving insomnia measured by overnight polysomnography measurements at three months, including sleep latency, total sleep time, and wake time after sleep onset.
2. To evaluate the efficacy of Daridorexant compared to placebo in improving both depressive symptoms in MDD patients at 3 months measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) and the MINI Scale.
3. To evaluate the safety of daridorexant compared to placebo in patients with major depressive disorder (MDD) and comorbid insomnia by monitoring for exacerbation of depressive symptoms and the emergence of suicidal ideation at baseline and three months.
4. To compare the side effect profile of daridorexant to placebo over a three -month period.
5. To evaluate the efficacy of Daridorexant compared to placebo in improving quality of life measured by EuroQuol in MDD patients after treatment of insomnia at 3 months.

Conditions and MedDRA coding

Patients with major depressive episode and moderate to severe insomnia disorder

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Age Range: 18-99 years old.
2. Patients with a current major depressive episode according to DSM-5, in a stable phase (defined as at least 4 weeks without significant changes in antidepressant treatment and no psychiatric hospitalizations in the previous 8 weeks) and with moderate or greater severity, as indicated by a total score of ≥ 20 on the Montgomery–Åsberg Depression Rating Scale (MADRS).
3. Insomnia disorder confirmed according to DSM-5
4. Informed Consent: Ability and willingness to provide written informed consent.
5. Acceptance of Protocol Requirements: Agreement to adhere to all scheduled visits, treatment plans, and study procedures.

Exclusion criteria 15

1. Other Current Psychiatric Disorders: Any current psychiatric disorder other than major depressive disorder (e.g., active psychotic disorders, mania, hypomania, acute schizophrenia, schizoaffective disorder).
2. Use of Non-Permitted Sleep Medications: Concurrent use of melatonin, benzodiazepines, sedative antidepressants or sedative antipsychotics use for insomnia not allowed by the protocol and unwillingness to follow the slow-taper schedule constitutes an exclusion criterion.
3. No concurrent sleep medications at least 30 days prior to baseline. Exclusion criteria if the patient has withdrawal symptoms and/or sleep disturbances measured by BWSQ prior to baseline.
4. Uncontrolled Severe Medical Conditions: Any condition that could interfere with study procedures, safety, or outcome measures (e.g., unstable cardiovascular, respiratory, neurological, or endocrine disorders).
5. Pregnancy or breastfeeding
6. Cognitive Impairments: Significant impairments that prevent the comprehension or completion of study questionnaires or procedures.
7. Hypersensitivity: Known allergy or hypersensitivity to daridorexant or any of its excipients.
8. Specific Sleep Disorders: Sleep apnea or hypopnea index ≥ 15 events/hour (based on American Academy of Sleep Medicine criteria) or any event associated with oxygen saturation < 80% (as measured by polysomnography).
9. Periodic limb movement index ≥ 15 events/hour (as measured by polysomnography). Restless legs syndrome, circadian rhythm sleep-wake disorders, REM behavior disorder, or narcolepsy.
10. Concomitant Use with Moderate and potent CYP3A4 Inhibitors: Prohibited due to potential drug interaction (refer to protocol section 4.5 for specifics).
11. Moderate and severe hepatic Impairment: Any hepatic condition deemed unsafe for daridorexant use.
12. Relapse or Worsening of the Main Diagnosis: Relapse of depression whose severity precludes continued participation according to the investigator’s judgment.
13. Substance Use Disorder: History of substance use disorder without sustained remission. Exception: past sedative abuse may be permissible if remission criteria are clearly met, as determined by the investigator.
14. Excessive Caffeine Intake: Daily consumption of >400 mg of caffeine (e.g., >4 standard cups of coffee).
15. High-Risk Alcohol Consumption: Alcohol intake above recommended risk thresholds (i.e., >4 standard drinks/day for men, >2 standard drinks/day for women).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Improvement in insomnia severity, measured by the Insomnia Severity Index (ISI) at 3 months.

Secondary endpoints 5

1. To evaluate the efficacy of Daridorexant compared with placebo in improving insomnia as measured by overnight polysomnography at 3 months, including sleep latency, total sleep time, wake after sleep onset.
2. To evaluate the efficacy of Daridorexant compared with placebo in improving depressive symptoms in patients with Major Depressive Disorder (MDD) at 3 months, measured by Montgomery–Åsberg Depression Rating Scale (MADRS), MINI Suicide Module.
3. To evaluate the safety of Daridorexant compared with placebo by monitoring worsening of depressive symptoms, emergence of suicidal ideation at baseline and at 3 months.
4. To compare the side-effect profile of Daridorexant with placebo over the 3-month treatment period.
5. To evaluate the efficacy of Daridorexant compared with placebo in improving quality of life, measured by the EuroQol (EQ-5D) after insomnia treatment at 3 months.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacio Institut D'Investigacio Biomedica De Bellvitge IDIBELL

Sponsor organisation

Fundacio Institut D'Investigacio Biomedica De Bellvitge IDIBELL

Address

Avinguda De La Gran Via De L'hospitalet 199

City

L'Hospitalet De Llobregat

Postcode

08908

Country

Spain

Scientific contact point

Organisation

Fundacio Institut D'Investigacio Biomedica De Bellvitge IDIBELL

Contact name

UICEC

Public contact point

Organisation

Fundacio Institut D'Investigacio Biomedica De Bellvitge IDIBELL

Contact name

UICEC

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 16 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications