DARIDOREXANT for Major depressive disorder | Insomnia disorder

Inclusion criteria

• {"criterion_text":"- Age Range: 18-99 years old."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- Insomnia disorder confirmed according to DSM-5"}
• {"criterion_text":"- Informed Consent: Ability and willingness to provide written informed consent."}
• {"criterion_text":"- Acceptance of Protocol Requirements: Agreement to adhere to all scheduled visits, treatment plans, and study procedures."}

Exclusion criteria

• {"criterion_text":"- Other Current Psychiatric Disorders: Any current psychiatric disorder other than major depressive disorder (e.g., active psychotic disorders, mania, hypomania, acute schizophrenia, schizoaffective disorder)."}
• {"criterion_text":"- Concomitant Use with Moderate and potent CYP3A4 Inhibitors: Prohibited due to potential drug interaction (refer to protocol section 4.5 for specifics)."}
• {"criterion_text":"- Moderate and severe hepatic Impairment: Any hepatic condition deemed unsafe for daridorexant use."}
• {"criterion_text":"- Relapse or Worsening of the Main Diagnosis: Relapse of depression whose severity precludes continued participation according to the investigator’s judgment."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Excessive Caffeine Intake: Daily consumption of >400 mg of caffeine (e.g., >4 standard cups of coffee)."}
• {"criterion_text":"- High-Risk Alcohol Consumption: Alcohol intake above recommended risk thresholds (i.e., >4 standard drinks/day for men, >2 standard drinks/day for women)."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- Pregnancy or breastfeeding"}
• {"criterion_text":"- Cognitive Impairments: Significant impairments that prevent the comprehension or completion of study questionnaires or procedures."}
• {"criterion_text":"- Hypersensitivity: Known allergy or hypersensitivity to daridorexant or any of its excipients."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- Periodic limb movement index ≥ 15 events/hour (as measured by polysomnography). Restless legs syndrome, circadian rhythm sleep-wake disorders, REM behavior disorder, or narcolepsy."}

Primary endpoints

• {"endpoint_text":"- Improvement in insomnia severity, measured by the Insomnia Severity Index (ISI) at 3 months.","definition_or_measurement_approach":"Measured by the Insomnia Severity Index (ISI) at 3 months."}

Secondary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Overnight polysomnography at 3 months measuring sleep latency, total sleep time, and wake after sleep onset."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Depressive symptoms measured at 3 months by the MADRS and MINI Suicide Module."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Safety evaluated by monitoring for worsening depressive symptoms and emergence of suicidal ideation at baseline and 3 months."}
• {"endpoint_text":"- To compare the side-effect profile of Daridorexant with placebo over the 3-month treatment period.","definition_or_measurement_approach":"Comparison of adverse event / side-effect profiles over the 3-month treatment period (as collected during study visits)."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Quality of life measured by EuroQol (EQ-5D) after treatment at 3 months."}

Spain

Earliest CTIS Part Ii Submission Date

24-03-2026

Latest Decision Or Authorization Date

04-05-2026

Processing Time Days

41

Number Of Sites

3

Number Of Participants

134

Primary sponsor

Full Name

Fundacio Institut D'Investigacio Biomedica De Bellvitge IDIBELL

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

Spain