InsomniaPhase 4NCT07555743
Efficacy and Safety of Daridorexant in Patients With Major Depressive Disorder and Insomnia
A Phase 4 study testing Daridorexant 50 mg in people with Insomnia and Major Depressive Disorder, run by Institut d'Investigació Biomèdica de Bellvitge at 1 site in Spain.
Trial summary
The goal of this clinical trial is to evaluate the efficacy and safety of Daridorexant in major depressive disorder (MDD) patients with comorbid insomnia. The main questions to answer are: 1. Does Daridorexant improve the severity of insomnia as measured by the Insomnia Severity Index (ISI)? 2. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Insomnia, Major Depressive Disorder
- What is being tested?
- Daridorexant 50 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 134 participants
- Where
- 1 siteSpain
- Study dates
- Apr 2026to Oct 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age Range: 18-99 years old.
- 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).
- Insomnia disorder confirmed according to DSM-5
- Insomnia Severity: Insomnia Severity Index (ISI) score = o >15.
- Medication Stability defined by :
Show all 10Show fewer
- Stable doses of antidepressants, mood stabilizers, or antipsychotics for at least 1 month prior to baseline (T0).
- Melatonin, Benzodiacepines, sedative antidepressants or sedative antipsychotics use for insomnia should follow a wash out protocol described below.
- Informed Consent: Ability and willingness to provide written informed consent.
- Acceptance of Protocol Requirements: Agreement to adhere to all scheduled visits, treatment plans, and study procedures.
Who cannot join
- Other Current Psychiatric Disorders: Any current psychiatric disorder other than major depressive disorder (e.g., active psychotic disorders, mania, hypomania, acute schizophrenia, schizoaffective disorder).
- 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.
- 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.
- 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).
- Pregnancy or breastfeeding
- Cognitive Impairments: Significant impairments that prevent the comprehension or completion of study questionnaires or procedures.
Show all 15Show fewer
- Hypersensitivity: Known allergy or hypersensitivity to daridorexant or any of its excipients.
- 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).
- Periodic limb movement index ≥ 15 events/hour (as measured by polysomnography). Restless legs syndrome, circadian rhythm sleep-wake disorders, REM behavior disorder, or narcolepsy.
- Concomitant Use with Moderate and potent CYP3A4 Inhibitors: Prohibited due to potential drug interaction (refer to protocol section 4.5 for specifics).
- Moderate and severe hepatic Impairment: Any hepatic condition deemed unsafe for daridorexant use.
- Relapse or Worsening of the Main Diagnosis: Relapse of depression whose severity precludes continued participation according to the investigator's judgment.
- 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.
- Excessive Caffeine Intake: Daily consumption of >400 mg of caffeine (e.g., >4 standard cups of coffee).
- High-Risk Alcohol Consumption: Alcohol intake above recommended risk thresholds in accordance with the guidelines of the Spanish Ministry of Health: i.e., >4 standard drinks/day (>40g/d) for men, >2 standard drinks/day (>20g/d) for women.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Efficacy and Safety of Daridorexant in Patients With Major Depressive Disorder (MDD) and Insomnia: Double-blind, Randomized, Controlled Trial
The goal of this clinical trial is to evaluate the efficacy and safety of Daridorexant in major depressive disorder (MDD) patients with comorbid insomnia. The main questions to answer are:
- Does Daridorexant improve the severity of insomnia as measured by the Insomnia Severity Index (ISI)?
- Does Daridorexant have an impact on depressive symptoms?
Read more
In order to address these questions, researchers will compare Daridorexant with a placebo to evaluate its impact on both insomnia and MDD-related symptoms.
Participants will:
- Receive Daridorexant or placebo for a duration of three months
- Complete a Sleep Diary and other questionnaires assessing sleep and depressive symptoms.
- Undergo polysomnography to obtain objective measurements of sleep parameters.
Read the detailed description
Insomnia is an extensively studied condition, yet its interactions with major depressive disorder (MDD) remain insufficiently understood. This study aims to evaluate the efficacy and safety of Daridorexant in MDD patients with comorbid insomnia. The primary objective is to determine whether Daridorexant improves the severity of insomnia, as measured by the Insomnia Severity Index (ISI), while assessing its impact on depressive symptoms will be considered the secondary objective. A prospective, double-blind, randomized, multicenter, placebo-controlled trial will be conducted in major depressive disorder outpatient clinic of the psychiatry department. Eligible patients will be randomized to Daridorexant versus placebo. Neither participants nor investigators will be aware of the treatment allocation. Standardized procedures for blinding and emergency unblinding will be implemented across all centers. The main outcome will be the improvement of Insomnia Severity Index (ISI) but additionally total sleep time, wake after sleep onset time, sleep latency and sleep efficiency will be measured. Data collection will include the Pittsburgh Sleep Quality Index (PSQI), depressive symptoms measured by the Montgomery-Åsberg Depression Rating Scale (MADRS), suicidal thoughts measured by the MINI-Neuropsychiatry Scale, quality of life measured by EuroQol, Dysfunctional Beliefs and Attitudes about Sleep (DBAS) and Polysomnography at baseline and 3 months. The study aims to demonstrate improvements in patient's subjective experience of insomnia, and additionally objective quantifiable improvements of objective sleep measurements via polysomnography, without an associated increase in depressive symptoms.
- Conditions
- Insomnia, Major Depressive Disorder
- Being tested
- Daridorexant 50 mg, Placebo
- Keywords
- Daridorexant, Clinical Trial, Insomnia, Major depressive disorder, Polysomnography, Insomnia Severity Index
- Medical subject headings
- Sleep Initiation and Maintenance Disorders, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Daridorexant 50 mgDrug
oral taking of Daridorexant 50mg/daily at bedtime, within 30 minutes of going to bed and at least 8-9 hours before planned wake time. Treatment duration: 12 weeks (3 months).
PlaceboDrug
Orally, once daily at bedtime, within 30 minutes of going to bed and at least 8-9 hours before planned wake time.
| Study group | Role | What they receive |
|---|---|---|
| Daridorexant 50mg | Experimental | Oral taking of Daridorexant, 50 mg/day for 3 months Receives: Drug: Daridorexant 50 mg |
| Placebo | Placebo comparator | Oral taking of placebo for 3 months Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insomnia Severity Index (ISI)
The Insomnia Severity Index is a widely used, self-reported questionnaire designed to assess the nature, severity, and impact of insomnia symptoms.
Each item is rated on a 5-point Likert scale from 0 to 4. The total score ranges from 0 to 28, with higher scores indicating greater insomnia severity.
According to the results insomnia will be classified as follows: 0-7: absence of clinical insomnia; 8-14: subclinical insomnia; 15-21: clinical insomnia; 22-28: severe insomnia.
Measured: ISI will be administered to all patients at baseline, and at months 1 and 3.
Secondary outcomes (18)
Sleep Efficiency (polysomnography)
•Sleep Efficiency (%): Total Sleep Time (minutes) / time in bed (minutes).
Measured: Polysomnography will be performed at baseline and at month 3.
Total Sleep Time (Polysomnography)
Total Sleep Time (TST): measured in minutes.
Measured: PSG will be performed at baseline and at month 3.
Wake After Sleep Onset (polysomnography)
Total number of minutes that a patient is awake after having initially fallen asleep.
Measured: Polysomnography will be performed at baseline and at month 3.
Arousal Index (polysomnography)
Number of arousals per hour of sleep.
Measured: Polysomnography will be performed at baseline and at month 3.
Cumulative time spent under 90% oxygen saturation (polysomnography)
[time under 90% oxygen saturation (min) / total sleep time (min)] · 100 (%)
Measured: Polysomnography will be performed at baseline and at month 3.
Periodic Leg Movement Index (Polysomnography)
number of leg movements per hour of sleep.
Measured: Polysomngraphy will be performed at baseline and at month 3.
Apnea-Hypopnea Index (polysomnography)
number of apneas and hypopneas per hour of sleep.
Measured: Polysomnography will be performed at baseline and at month 3.
Pittsburg Sleep Quality Index (PSQI)
Each item is rated on a 4-point Likert scale from 0 to 3. The total score varies between 0 and 21, with higher scores indicating greater difficulties with sleep.
Measured: PSQI will be administered to all patients at baseline, and at months 1 and 3.
Dysfunctional Beliefs and Attitudes about Sleep (DBAS)
Each item is rated on a 5-point Likert scale from 1 to 5. The total score ranges from 30 to 150, with lower scores indicating a greater presence of dysfunctional beliefs and attitudes about sleep.
Measured: The DBAS will be administered to all patients at baseline, and at months 1 and 3.
Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ)
The IDSIQ is a patient-reported outcome measure assessing daytime functioning impairments associated with insomnia. It comprises 14 items, each rated on a 0-10 scale. Items are summed to obtain a total score (range: 0-140).
Interpretation:
Higher scores indicate greater daytime impairment related to insomnia.
Measured: The IDSIQ will be administered daily to all patients from baseline through month 3.
Montgomery-Åsberg Depression Rating Scale (MADRS)
The assessment should be based on a clinical interview that ranges from general questions about symptoms to more detailed questions that allow for a precise evaluation of severity. The evaluator must decide whether the assessment corresponds to the responses defined at the levels of the scale (0, 2, 4, 6) or to those between them (1, 3, 5). The total score ranges from 0 to 60.
Interpretation: No depression (0-6); mild (7-19); moderate (20-34); severe (35-60).
Measured: MADRS will be administered to all patients at baseline, and at months 1 and 3.
Suicidal Scale of the Mini-International Neuropsychiatric Interview (MINI)
Only the suicide item of the MINI will be administered.
Each item is scored dichotomously (Yes/No). Points are assigned to "Yes" responses and summed to yield a total score:
Wish to be dead: 1 point Self-harm desire: 2 points Suicidal ideation: 6 points Suicide plan: 10 points Suicide attempt (past month): 10 points Lifetime suicide attempt: 4 points
Total score range: 0-33
Risk categories:
0: No risk 1-5: Low risk 6-9: Moderate risk
≥10: High risk
Measured: Will be administered to all patients at baseline and at months 1 and 3.
EuroQol-5D-5L
The EQ-5D-5L comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), each rated on ordered levels.
Each item is rated on a 5-point Likert scale from 1 to 5. The total score ranges from 5 to 25, with higher scores indicating poorer health status. The instrument also includes a visual analogue scale, where pacients rate their overall health from 0 (worst imaginable health) to 100 (best imaginable health).
Measured: Will be administered at baseline and at month 3.
Sleep onset (Sleep diary)
Time in minutes between attempting to fall asleep and the onset of sleep.
Measured: The sleep diary will be administered at baseline and at months 1 and 3, for seven consecutive days prior to each visit.
Sleep latency (Sleep diary)
Time interval between attempting to initiate sleep (lights-off) and the onset of sleep, as measured in minutes.
Measured: The sleep diary will be administered at baseline and at months 1 and 3, for seven consecutive days prior to each visit.
Wakefulness after sleep onset (sleep diary)
Total duration of time spent awake after initial sleep onset and before final awakening, as measured in minutes.
Measured: The sleep diary will be administered at baseline and at months 1 and 3, for seven consecutive days prior to each visit.
Total sleep time (sleep diary)
Total Sleep Time (TST): measured in minutes.
Measured: The sleep diary will be administered at baseline and at months 1 and 3, for seven consecutive days prior to each visit.
Total time spent in bed (sleep diary)
Time spent by the patient at bed, as measured in minutes.
Measured: The sleep diary will be administered at baseline and at months 1 and 3, for seven consecutive days prior to each visit.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2026
- Study startApr 2026 (estimated)
- Primary completionApr 2027 (estimated)
- Study completionOct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (22)Papers the sponsor has linked to this study.
- Other trials for InsomniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 134 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Institut d'Investigació Biomèdica de Bellvitge
- Sponsor type
- University, hospital or other
- Collaborators
- Idorsia Pharmaceuticals Ltd., Hospital Universitari de Bellvitge
- Responsible party
- Principal investigator, Sara Lakis Granell, Institut d'Investigació Biomèdica de Bellvitge
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07555743
- Sponsor's protocol ID
- SEDA
- Status last verified
- Apr 2026
- First submitted
- 9 Apr 2026
- Last updated
- 29 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Personal data will not be transferred in this trial and will be anonymized.
Publications
Xu G, Li X, Xu C, Xie G, Liang J. Effect of insomnia in the major depressive disorder. BMC Neurol. 2022 Sep 10;22(1):341. doi: 10.1186/s12883-022-02869-x.
PubMed 36088310Watson NF, Benca RM, Krystal AD, McCall WV, Neubauer DN. Alliance for Sleep Clinical Practice Guideline on Switching or Deprescribing Hypnotic Medications for Insomnia. J Clin Med. 2023 Mar 25;12(7):2493. doi: 10.3390/jcm12072493.
PubMed 37048577GBD 2019 Diseases and Injuries Collaborators. Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020 Oct 17;396(10258):1204-1222. doi: 10.1016/S0140-6736(20)30925-9.
PubMed 33069326Ugurlu M. Orexin Receptor Antagonists as Adjunct Drugs for the Treatment of Depression: A Mini Meta-Analysis. Noro Psikiyatr Ars. 2023 Jun 19;61(1):77-84. doi: 10.29399/npa.28383. eCollection 2024.
PubMed 38496221Scott MM, Marcus JN, Pettersen A, Birnbaum SG, Mochizuki T, Scammell TE, Nestler EJ, Elmquist JK, Lutter M. Hcrtr1 and 2 signaling differentially regulates depression-like behaviors. Behav Brain Res. 2011 Sep 23;222(2):289-94. doi: 10.1016/j.bbr.2011.02.044. Epub 2011 Mar 4.
PubMed 21377495Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, Niederehe G, Thase ME, Lavori PW, Lebowitz BD, McGrath PJ, Rosenbaum JF, Sackeim HA, Kupfer DJ, Luther J, Fava M. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006 Nov;163(11):1905-17. doi: 10.1176/ajp.2006.163.11.1905.
PubMed 17074942Palagini L, Brugnoli R, Dell' Osso BM, Di Nicola M, Maina G, Martinotti G, Maruani J, Mauries S, Serafini G, Mencacci C, Liguori C, Ferini-Strambi L, Geoffroy PA, Balestrieri M. Clinical practice guidelines for switching or deprescribing hypnotic medications for chronic insomnia: Results of European neuropsychopharmacology and sleep expert's consensus group. Sleep Med. 2025 Apr;128:117-126. doi: 10.1016/j.sleep.2025.01.033. Epub 2025 Jan 31.
PubMed 39923608Palagini L, Miniati M, Marazziti D, Riemann D, Geoffroy PA, Gemignani A. Effects of Approved Pharmacological Interventions for Insomnia on Mood Disorders: A Systematic Review. Clin Neuropsychiatry. 2024 Oct;21(5):385-402. doi: 10.36131/cnfioritieditore20240504.
PubMed 39540072Palagini L, Alfi G, Gurrieri R, Annuzzi E, Caruso V, Gambini M, Grenno G, Trivella M, Presta S, Miniati M, Pini S, Perugi G, Gemignani A. Early experience with the new DORA daridorexant in patients with insomnia disorder and comorbid mental disturbances: Results of a naturalistic study with 3 months follow-up. J Sleep Res. 2024 Dec;33(6):e14196. doi: 10.1111/jsr.14196. Epub 2024 Mar 24.
PubMed 38522432Na HJ, Jeon N, Staatz CE, Han N, Baek IH. Clinical safety and narcolepsy-like symptoms of dual orexin receptor antagonists in patients with insomnia: a systematic review and meta-analysis. Sleep. 2024 Feb 8;47(2):zsad293. doi: 10.1093/sleep/zsad293.
PubMed 37950346Morin CM, Stone J, Trinkle D, Mercer J, Remsberg S. Dysfunctional beliefs and attitudes about sleep among older adults with and without insomnia complaints. Psychol Aging. 1993 Sep;8(3):463-7. doi: 10.1037//0882-7974.8.3.463.
PubMed 8216967Mignot E, Mayleben D, Fietze I, Leger D, Zammit G, Bassetti CLA, Pain S, Kinter DS, Roth T; investigators. Safety and efficacy of daridorexant in patients with insomnia disorder: results from two multicentre, randomised, double-blind, placebo-controlled, phase 3 trials. Lancet Neurol. 2022 Feb;21(2):125-139. doi: 10.1016/S1474-4422(21)00436-1.
PubMed 35065036Meshkat S, Kwan ATH, Le GH, Wong S, Teopiz KM, Wang L, Rosenblat JD, Rhee TG, Cao B, McIntyre RS. Efficacy of orexin antagonists for the management of major depressive disorder: A systematic review of randomized clinical trials. J Affect Disord. 2025 Mar 1;372:409-419. doi: 10.1016/j.jad.2024.12.008. Epub 2024 Dec 4.
PubMed 39638064McCall WV, Blocker JN, D'Agostino R Jr, Kimball J, Boggs N, Lasater B, Haskett R, Krystal A, McDonald WM, Rosenquist PB. Treatment of insomnia in depressed insomniacs: effects on health-related quality of life, objective and self-reported sleep, and depression. J Clin Sleep Med. 2010 Aug 15;6(4):322-9.
PubMed 20726279Lin HT, Lai CH, Perng HJ, Chung CH, Wang CC, Chen WL, Chien WC. Insomnia as an independent predictor of suicide attempts: a nationwide population-based retrospective cohort study. BMC Psychiatry. 2018 May 2;18(1):117. doi: 10.1186/s12888-018-1702-2.
PubMed 29716570
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Daridorexant in Patients With Major Depressive Disorder (MDD) and Insomnia: Double-blind, Randomized, Controlled Trial
- ClinicalTrials.gov ID
- NCT07555743
- Acronym / sponsor ID
- SEDA
- Conditions
- Insomnia, Major Depressive Disorder
- Keywords
- Daridorexant, Clinical Trial, Insomnia, Major depressive disorder, Polysomnography, Insomnia Severity Index
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 134 participants (estimated)
- Lead sponsor
- Institut d'Investigació Biomèdica de BellvitgeUniversity, hospital or other
- Collaborators
- Idorsia Pharmaceuticals Ltd., Hospital Universitari de Bellvitge
- Study start
- Apr 2026 (estimated)
- Primary completion
- Apr 2027 (estimated)
- Study completion
- Oct 2028 (estimated)
- First posted
- 29 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to evaluate the efficacy and safety of Daridorexant in major depressive disorder (MDD) patients with comorbid insomnia. The main questions to answer are:
- Does Daridorexant improve the severity of insomnia as measured by the Insomnia Severity Index (ISI)?
- Does Daridorexant have an impact on depressive symptoms?
In order to address these questions, researchers will compare Daridorexant with a placebo to evaluate its impact on both insomnia and MDD-related symptoms.
Participants will:
- Receive Daridorexant or placebo for a duration of three months
- Complete a Sleep Diary and other questionnaires assessing sleep and depressive symptoms.
- Undergo polysomnography to obtain objective measurements of sleep parameters.
Detailed description
Insomnia is an extensively studied condition, yet its interactions with major depressive disorder (MDD) remain insufficiently understood. This study aims to evaluate the efficacy and safety of Daridorexant in MDD patients with comorbid insomnia. The primary objective is to determine whether Daridorexant improves the severity of insomnia, as measured by the Insomnia Severity Index (ISI), while assessing its impact on depressive symptoms will be considered the secondary objective. A prospective, double-blind, randomized, multicenter, placebo-controlled trial will be conducted in major depressive disorder outpatient clinic of the psychiatry department. Eligible patients will be randomized to Daridorexant versus placebo. Neither participants nor investigators will be aware of the treatment allocation. Standardized procedures for blinding and emergency unblinding will be implemented across all centers. The main outcome will be the improvement of Insomnia Severity Index (ISI) but additionally total sleep time, wake after sleep onset time, sleep latency and sleep efficiency will be measured. Data collection will include the Pittsburgh Sleep Quality Index (PSQI), depressive symptoms measured by the Montgomery-Åsberg Depression Rating Scale (MADRS), suicidal thoughts measured by the MINI-Neuropsychiatry Scale, quality of life measured by EuroQol, Dysfunctional Beliefs and Attitudes about Sleep (DBAS) and Polysomnography at baseline and 3 months. The study aims to demonstrate improvements in patient's subjective experience of insomnia, and additionally objective quantifiable improvements of objective sleep measurements via polysomnography, without an associated increase in depressive symptoms.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Daridorexant 50mg | Experimental | Drug: Daridorexant 50 mgOral taking of Daridorexant, 50 mg/day for 3 months |
| Placebo | Placebo comparator | Drug: PlaceboOral taking of placebo for 3 months |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Age Range: 18-99 years old.
- 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
- Insomnia disorder confirmed according to DSM-5
- Informed Consent: Ability and willingness to provide written informed consent.
- Acceptance of Protocol Requirements: Agreement to adhere to all scheduled visits, treatment plans, and study procedures.
Key exclusion criteria (15 listed)
- Other Current Psychiatric Disorders: Any current psychiatric disorder other than major depressive disorder (e.g., active psychotic disorders, mania, hypomania, acute schizophrenia, schizoaffective disorder).
- 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.
- 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.
- 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).
- Pregnancy or breastfeeding
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Daridorexant 50 mgoral taking of Daridorexant 50mg/daily at bedtime, within 30 minutes of going to bed and at least 8-9 hours before planned wake time. Treatment duration: 12 weeks (3 months). | Drug | Daridorexant 50mg |
| PlaceboOrally, once daily at bedtime, within 30 minutes of going to bed and at least 8-9 hours before planned wake time. | Drug | Placebo |
Primary outcome
Insomnia Severity Index (ISI)
Time frame: ISI will be administered to all patients at baseline, and at months 1 and 3.
The Insomnia Severity Index is a widely used, self-reported questionnaire designed to assess the nature, severity, and impact of insomnia symptoms. Each item is rated on a 5-point Likert scale from 0 to 4. The total score ranges from 0 to 28, with higher scores indicating greater insomnia severity. According to the results insomnia will be classified as follows: 0-7: absence of clinical insomnia; 8-14: subclinical insomnia; 15-21: clinical insomnia; 22-28: severe insomnia.
18 secondary outcomes
Sleep Efficiency (polysomnography)
Time frame: Polysomnography will be performed at baseline and at month 3.
Total Sleep Time (Polysomnography)
Time frame: PSG will be performed at baseline and at month 3.
Wake After Sleep Onset (polysomnography)
Time frame: Polysomnography will be performed at baseline and at month 3.
Arousal Index (polysomnography)
Time frame: Polysomnography will be performed at baseline and at month 3.
Cumulative time spent under 90% oxygen saturation (polysomnography)
Time frame: Polysomnography will be performed at baseline and at month 3.
Periodic Leg Movement Index (Polysomnography)
Time frame: Polysomngraphy will be performed at baseline and at month 3.
Apnea-Hypopnea Index (polysomnography)
Time frame: Polysomnography will be performed at baseline and at month 3.
Pittsburg Sleep Quality Index (PSQI)
Time frame: PSQI will be administered to all patients at baseline, and at months 1 and 3.
Dysfunctional Beliefs and Attitudes about Sleep (DBAS)
Time frame: The DBAS will be administered to all patients at baseline, and at months 1 and 3.
Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ)
Time frame: The IDSIQ will be administered daily to all patients from baseline through month 3.
Montgomery-Åsberg Depression Rating Scale (MADRS)
Time frame: MADRS will be administered to all patients at baseline, and at months 1 and 3.
Suicidal Scale of the Mini-International Neuropsychiatric Interview (MINI)
Time frame: Will be administered to all patients at baseline and at months 1 and 3.
EuroQol-5D-5L
Time frame: Will be administered at baseline and at month 3.
Sleep onset (Sleep diary)
Time frame: The sleep diary will be administered at baseline and at months 1 and 3, for seven consecutive days prior to each visit.
Sleep latency (Sleep diary)
Time frame: The sleep diary will be administered at baseline and at months 1 and 3, for seven consecutive days prior to each visit.
Wakefulness after sleep onset (sleep diary)
Time frame: The sleep diary will be administered at baseline and at months 1 and 3, for seven consecutive days prior to each visit.
Total sleep time (sleep diary)
Time frame: The sleep diary will be administered at baseline and at months 1 and 3, for seven consecutive days prior to each visit.
Total time spent in bed (sleep diary)
Time frame: The sleep diary will be administered at baseline and at months 1 and 3, for seven consecutive days prior to each visit.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2026.
- Background: PubMed 36088310Xu G, Li X, Xu C, Xie G, Liang J. Effect of insomnia in the major depressive disorder. BMC Neurol. 2022 Sep 10;22(1):341. doi: 10.1186/s12883-022-02869-x.
- Background: PubMed 37048577Watson NF, Benca RM, Krystal AD, McCall WV, Neubauer DN. Alliance for Sleep Clinical Practice Guideline on Switching or Deprescribing Hypnotic Medications for Insomnia. J Clin Med. 2023 Mar 25;12(7):2493. doi: 10.3390/jcm12072493.
- Background: PubMed 33069326GBD 2019 Diseases and Injuries Collaborators. Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020 Oct 17;396(10258):1204-1222. doi: 10.1016/S0140-6736(20)30925-9.
- Background: PubMed 38496221Ugurlu M. Orexin Receptor Antagonists as Adjunct Drugs for the Treatment of Depression: A Mini Meta-Analysis. Noro Psikiyatr Ars. 2023 Jun 19;61(1):77-84. doi: 10.29399/npa.28383. eCollection 2024.
- Background: PubMed 21377495Scott MM, Marcus JN, Pettersen A, Birnbaum SG, Mochizuki T, Scammell TE, Nestler EJ, Elmquist JK, Lutter M. Hcrtr1 and 2 signaling differentially regulates depression-like behaviors. Behav Brain Res. 2011 Sep 23;222(2):289-94. doi: 10.1016/j.bbr.2011.02.044. Epub 2011 Mar 4.
- Background: PubMed 17074942Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, Niederehe G, Thase ME, Lavori PW, Lebowitz BD, McGrath PJ, Rosenbaum JF, Sackeim HA, Kupfer DJ, Luther J, Fava M. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006 Nov;163(11):1905-17. doi: 10.1176/ajp.2006.163.11.1905.
- Background: PubMed 39923608Palagini L, Brugnoli R, Dell' Osso BM, Di Nicola M, Maina G, Martinotti G, Maruani J, Mauries S, Serafini G, Mencacci C, Liguori C, Ferini-Strambi L, Geoffroy PA, Balestrieri M. Clinical practice guidelines for switching or deprescribing hypnotic medications for chronic insomnia: Results of European neuropsychopharmacology and sleep expert's consensus group. Sleep Med. 2025 Apr;128:117-126. doi: 10.1016/j.sleep.2025.01.033. Epub 2025 Jan 31.
- Background: PubMed 39540072Palagini L, Miniati M, Marazziti D, Riemann D, Geoffroy PA, Gemignani A. Effects of Approved Pharmacological Interventions for Insomnia on Mood Disorders: A Systematic Review. Clin Neuropsychiatry. 2024 Oct;21(5):385-402. doi: 10.36131/cnfioritieditore20240504.
- Background: PubMed 38522432Palagini L, Alfi G, Gurrieri R, Annuzzi E, Caruso V, Gambini M, Grenno G, Trivella M, Presta S, Miniati M, Pini S, Perugi G, Gemignani A. Early experience with the new DORA daridorexant in patients with insomnia disorder and comorbid mental disturbances: Results of a naturalistic study with 3 months follow-up. J Sleep Res. 2024 Dec;33(6):e14196. doi: 10.1111/jsr.14196. Epub 2024 Mar 24.
- Background: PubMed 37950346Na HJ, Jeon N, Staatz CE, Han N, Baek IH. Clinical safety and narcolepsy-like symptoms of dual orexin receptor antagonists in patients with insomnia: a systematic review and meta-analysis. Sleep. 2024 Feb 8;47(2):zsad293. doi: 10.1093/sleep/zsad293.
- Background: PubMed 8216967Morin CM, Stone J, Trinkle D, Mercer J, Remsberg S. Dysfunctional beliefs and attitudes about sleep among older adults with and without insomnia complaints. Psychol Aging. 1993 Sep;8(3):463-7. doi: 10.1037//0882-7974.8.3.463.
- Background: PubMed 35065036Mignot E, Mayleben D, Fietze I, Leger D, Zammit G, Bassetti CLA, Pain S, Kinter DS, Roth T; investigators. Safety and efficacy of daridorexant in patients with insomnia disorder: results from two multicentre, randomised, double-blind, placebo-controlled, phase 3 trials. Lancet Neurol. 2022 Feb;21(2):125-139. doi: 10.1016/S1474-4422(21)00436-1.
- Individual participant dataSharing planned: No. Personal data will not be transferred in this trial and will be anonymized.
Related trials for Insomnia
Recruiting
Addressing Nocturia in Older Women Utilizing Behavioral Sleep Intervention and Brief Mindfulness
Nocturia, Insomnia
Not yet recruiting
A Transdiagnostic Sleep Health Intervention for Veterans With PTSD
Stress Disorders, Post-Traumatic, Sleep Initiation and Maintenance Disorders
Recruiting
Effect of Cyclic Sighing Breathing Exercise on CRBD, Pain, and Sleep Quality in Patients Undergoing TUR
Transurethral Resection of Bladder Tumor, Transurethral Resection of the Prostate (TURP)
Recruiting
Evaluation of Cognitive Behavioral Therapy for Insomnia (CBT-I) in Individuals With Mild Traumatic Brain Injury (mTBI)
Sleep Architecture, Mild Traumatic Brain Injury
RecruitingPhase 3
A Trial to See if Daridorexant Can Help Adults and Elderly People With Insomnia Sleep Better During the Night and Function Better During the Day
Insomia Disorder
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Daridorexant 50 mg in people with Insomnia and Major Depressive Disorder, run by Institut d'Investigació Biomèdica de Bellvitge at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 29 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sara Lakis Granell, MD (+34 932 60 79 22, slakis@bellvitgehospital.cat), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Insomnia Severity Index (ISI) (time frame: ISI will be administered to all patients at baseline, and at months 1 and 3.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07555743, which also lists 22 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2026.