drugset / Trial / NCT07555743
Efficacy and Safety of Daridorexant in Patients With Major Depressive Disorder and Insomnia
Phase 4
Not yet recruiting
134 enrolled
Bellvitge Biomedical Research Institute
Hospital Universitari de Bellvitge · collabIdorsia Pharmaceuticals Ltd. · collab
RandomizedParallel-groupTriple-blindTreatment
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. 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.
Timeline
- Start
- 2026-04
- Primary completion
- 2027-04
- Completion
- 2028-10
Publications
- Background 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.
- Background Watson 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 GBD 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 Ugurlu 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 Scott 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 Rush 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 Palagini 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 Palagini 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 Palagini 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 Na 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 Morin 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 Mignot 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.
- Background Meshkat 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.
- Background McCall 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.
- Background Lin 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.
- Background Hintze JP, Edinger JD. Hypnotic Discontinuation in Chronic Insomnia. Sleep Med Clin. 2020 Jun;15(2):147-154. doi: 10.1016/j.jsmc.2020.02.003.
- Background Heerlein K, Perugi G, Otte C, Frodl T, Degraeve G, Hagedoorn W, Oliveira-Maia AJ, Perez Sola V, Rathod S, Rosso G, Sierra P, Malynn S, Morrens J, Verrijcken C, Gonzalez B, Young AH. Real-world evidence from a European cohort study of patients with treatment resistant depression: Treatment patterns and clinical outcomes. J Affect Disord. 2021 Jul 1;290:334-344. doi: 10.1016/j.jad.2021.03.073. Epub 2021 Apr 1.
- Background Guerrera CS, Boccaccio FM, Varrasi S, Platania GA, Coco M, Pirrone C, Castellano S, Caraci F, Ferri R, Lanza G. A narrative review on insomnia and hypersomnolence within Major Depressive Disorder and bipolar disorder: A proposal for a novel psychometric protocol. Neurosci Biobehav Rev. 2024 Mar;158:105575. doi: 10.1016/j.neubiorev.2024.105575. Epub 2024 Feb 6.
- Background Greenberg PE, Fournier AA, Sisitsky T, Simes M, Berman R, Koenigsberg SH, Kessler RC. The Economic Burden of Adults with Major Depressive Disorder in the United States (2010 and 2018). Pharmacoeconomics. 2021 Jun;39(6):653-665. doi: 10.1007/s40273-021-01019-4. Epub 2021 May 5.
- Background Grafe LA, Eacret D, Dobkin J, Bhatnagar S. Reduced Orexin System Function Contributes to Resilience to Repeated Social Stress. eNeuro. 2018 Apr 16;5(2):ENEURO.0273-17.2018. doi: 10.1523/ENEURO.0273-17.2018. eCollection 2018 Mar-Apr.
- Background Fagan H, Jones E, Baldwin DS. Orexin Receptor Antagonists in the Treatment of Depression: A Leading Article Summarising Pre-clinical and Clinical Studies. CNS Drugs. 2023 Jan;37(1):1-12. doi: 10.1007/s40263-022-00974-6. Epub 2022 Nov 27.
- Background Baimel C, Borgland SL. Hypocretin modulation of drug-induced synaptic plasticity. Prog Brain Res. 2012;198:123-31. doi: 10.1016/B978-0-444-59489-1.00008-2.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Daridorexant | Small molecule | 50 mg | Oral |