What Is Daridorexant?
Daridorexant is an FDA-approved medication for insomnia. Insomnia, or trouble sleeping, is a common condition affecting about 1 in 10 adults, where individuals are not satisfied with how long or how well they sleep. This condition has been linked to various health issues, including depression, heart disease, and memory problems. Daridorexant is an orally administered drug, typically taken once daily at bedtime. Clinical trials have investigated daridorexant for its potential to help people with sleep difficulties, including those with insomnia disorder. The medication is generally taken within 30 minutes of going to bed, ensuring 8-9 hours before planned wake time. Daridorexant has been studied in a total of 31 trials involving 9,276 participants. The first trial began on 2018-06-04, and the latest is expected to conclude on 2026-04-29. While the specific biological mechanism of how daridorexant works is not detailed in the provided trial descriptions, it is studied as an active treatment to improve sleep quality and duration.
Uses and Conditions Under Study
Daridorexant is primarily studied for various sleep-related conditions. The most common focus is insomnia disorder, a condition characterized by difficulty falling or staying asleep, or poor quality sleep. Daridorexant aims to improve sleep in these individuals, and it has been investigated in 17 trials across Insomnia Disorder, Insomnia, Insomnia Chronic, and general Sleep studies. One trial description notes its use in smokers with insomnia, highlighting its potential role in managing sleep disturbances associated with tobacco use and withdrawal, which is a major risk factor for relapse.
Beyond primary insomnia, daridorexant is also being explored for its effects on other neurological and mental health conditions. This includes Post Traumatic Stress Disorder (PTSD), where sleep disturbances are a common symptom. It is also under investigation for Major Depressive Disorder, Emotional Processing, and Learning, with a total of 5 trials exploring these areas. These studies aim to understand if improving sleep with daridorexant could have broader benefits on mood, cognitive function, and the processing of emotions.
Furthermore, daridorexant is studied in healthy volunteers. These 8 trials in healthy individuals are typically conducted to understand how the drug is absorbed, distributed, metabolized, and excreted by the body (pharmacokinetics) and to assess its safety profile before or alongside studies in patient populations. This helps researchers determine appropriate dosing and potential side effects.
Dosing
Daridorexant is administered orally, typically as a tablet or capsule. The most frequently studied dose for insomnia is 50 mg, taken once daily at bedtime. Trial descriptions specify that this dose should be taken within 30 minutes of going to bed, ensuring at least 8 to 9 hours before planned wake time. This regimen has been studied for durations such as 12 weeks (3 months) and up to 1 year.
Beyond the 50 mg dose, several other strengths of daridorexant have been investigated in clinical trials. These include 10 mg, 25 mg, and 200 mg. These varying dosages are often explored in studies to determine the optimal effective dose, to understand dose-response relationships, or to assess safety and tolerability across a range of exposures. Some trials also involve daridorexant in combination with other medications, such as midazolam, warfarin, famotidine, or efavirenz, to study potential drug interactions. There is no information provided regarding pediatric dosing; all described dosages appear to be for adult use.
Side Effects
In clinical trials, the most common side effect reported by patients taking Daridorexant was nasopharyngitis (common cold symptoms). Across three trials involving 1779 patients in the drug arm, 7.7% of patients taking Daridorexant experienced nasopharyngitis, compared to 7.0% of patients taking a placebo.
Other side effects observed in clinical trials included:
- Headache: 5.6% of patients taking Daridorexant experienced headache, compared to 4.0% on placebo (across three trials with 1237 patients in the drug arm).
- Fatigue: 5.0% of patients taking Daridorexant experienced fatigue, compared to 0.0% on placebo (in one trial with 60 patients in the drug arm).
- Dry mouth: 5.0% of patients taking Daridorexant experienced dry mouth, compared to 3.4% on placebo (in one trial with 60 patients in the drug arm).
Clinical Trial Results
Daridorexant for Insomnia Disorder
Two major studies (NCT03545191 and NCT03575104) evaluated the effectiveness of Daridorexant for insomnia. Results showed improvements in sleep onset, sleep maintenance, total sleep time, and daytime sleepiness.
In one study (NCT03545191), patients taking Daridorexant 50 mg experienced:
- Faster sleep onset (Latency to Persistent Sleep, LPS): After one month, patients fell asleep an average of 31.20 minutes faster, compared to 19.85 minutes faster for those on placebo. After three months, this improved to 34.80 minutes faster, compared to 23.13 minutes faster for placebo.
- More total sleep time (Subjective Total Sleep Time, sTST): After one month, patients slept an average of 43.62 minutes more per night, compared to 21.56 minutes more for those on placebo. After three months, this increased to 57.67 minutes more, compared to 37.90 minutes more for placebo.
- Less waking during the night (Wake After Sleep Onset, WASO): After one month, patients spent 28.98 minutes less time awake after initially falling asleep, compared to 6.20 minutes less for those on placebo. After three months, this was 29.41 minutes less, compared to 11.11 minutes less for placebo.
- Reduced daytime sleepiness (IDSIQ Sleepiness Domain Score): Scores improved by 3.77 points after one month and 5.70 points after three months, compared to improvements of 2.02 points and 3.79 points for placebo, respectively (lower scores indicate less sleepiness).
Another study (NCT03575104) with Daridorexant 25 mg showed similar benefits:
- Faster sleep onset: After one month, patients fell asleep an average of 26.46 minutes faster, compared to 20.01 minutes faster for those on placebo. After three months, this was 28.91 minutes faster, compared to 19.89 minutes faster for placebo.
- More total sleep time: After one month, patients slept an average of 43.77 minutes more per night, compared to 27.64 minutes more for those on placebo. After three months, this increased to 56.18 minutes more, compared to 37.12 minutes more for placebo.
- Less waking during the night: After one month, patients spent 24.19 minutes less time awake after initially falling asleep, compared to 12.57 minutes less for those on placebo. After three months, this was 24.25 minutes less, compared to 14.00 minutes less for placebo.
Daridorexant for Insomnia and Nocturia
A study (NCT05597020) in patients with insomnia and frequent nighttime urination (nocturia) showed that Daridorexant 50 mg improved sleep and slightly reduced nocturnal voids. After four weeks, patients taking Daridorexant 50 mg slept an average of 56.6 minutes more per night, compared to 35.7 minutes more for those on placebo. They also experienced 1.6 fewer nocturnal voids on average, compared to 1.3 fewer for those on placebo.
Daridorexant for Delirium Prevention
A study (NCT06630390) investigating Daridorexant to prevent delirium after heart surgery reported that 5 participants in the Daridorexant arm experienced delirium, compared to 5 to 6 participants in the placebo arm. Sleep disturbance was reported by 5 participants in the Daridorexant arm and 5 to 6 participants in the placebo arm.
Currently Recruiting Trials
Daridorexant is currently being investigated in several clinical trials, exploring its potential benefits for various conditions beyond its approved use. These studies aim to gather more information about its effects, safety, and how it compares to other treatments.
- One Phase 4 study, NCT07136415, sponsored by Brigham and Women's Hospital, is comparing daridorexant with digital therapy (Cognitive Behavioral Therapy for Insomnia) and trazodone for insomnia symptoms in peri- and post-menopausal women. This trial seeks to enroll 1000 participants to understand the comparative effectiveness and safety of these three approaches.
- The Douglas Mental Health University Institute is sponsoring a Phase 2 study, NCT07213349, investigating daridorexant 50 mg for Alzheimer's disease prevention. This study aims to enroll 240 participants who do not currently have Alzheimer's disease dementia, to see if the medication can support brain health by clearing proteins linked to the disease.
- A Phase 2 pilot trial, NCT07217912, from the University of Rochester, is evaluating daridorexant for preventing postoperative delirium after heart surgery. This study is recruiting 80 participants to gather preliminary data for a larger future trial.
- At the University of Oxford, a Phase 4 study, NCT07267559, is examining how daridorexant affects human behavior and brain function, specifically focusing on learning, cognitive functioning, and emotional processing. This trial is open to 62 participants.
- Idorsia Pharmaceuticals Ltd. is conducting a registry study, NCT06498128, to collect information on pregnancy, neonatal, and infant outcomes in women exposed to QUVIVIQ® (daridorexant) during pregnancy. This registry aims to include 785 participants to compare outcomes with women not exposed to the medication.
- For patients with mild cognitive impairment and mild to moderate Alzheimer's disease who also experience insomnia, the University Hospital, Montpellier, is sponsoring a Phase 4 study, NCT05924425. This trial is evaluating the efficacy and safety of daridorexant 50 mg in 62 participants.
- Finally, daridorexant is also being investigated as Intervention C in a Phase 2 adaptive platform trial for Post Traumatic Stress Disorder (PTSD), sponsored by the Global Coalition for Adaptive Research. The specific arm for daridorexant, NCT05948540, aims to enroll 200 participants to assess its safety and efficacy in individuals with PTSD. This intervention is part of a larger master protocol, NCT05422612, which evaluates multiple potential treatments for PTSD.
Where to Participate
Clinical trials for daridorexant are currently recruiting participants across a wide geographical area, with studies active in 17 cities across 15 states. This broad reach helps ensure diverse participation in research efforts.
Some of the locations with active studies include:
- Williamsville, New York
- Fort Thomas, Kentucky
- Bethesda, Maryland
- Miami, Florida
- San Antonio, Texas
- Atlanta, Georgia
- Fort Belvoir, Virginia
- Joint Base Lewis McChord, Washington
- Tripler AMC, Hawaii
- Rochester, New York
Eligibility criteria for these trials generally welcome a wide range of individuals, including healthy volunteers and children. Participants typically range in age from 15 to 90 years, and studies are open to all genders.
Development Timeline
The journey of daridorexant in clinical research began on June 4, 2018, marking the start of its extensive development. Since then, a total of 31 clinical trials have been initiated, enrolling over 9,276 participants to investigate its potential across various health conditions.
Idorsia Pharmaceuticals Ltd. has been a primary driver of this research, sponsoring 15 of these trials. Other institutions and organizations, such as the Global Coalition for Adaptive Research and the University of Rochester, have also contributed significantly to the research landscape.
Early investigations initially explored conditions like Irritable Bowel Syndrome with Constipation (IBS-C) and hyperphosphatemia. Over time, the research pipeline for daridorexant expanded considerably. It moved through different phases of development, including 9 Phase 1 trials, 7 Phase 2 trials, and 5 Phase 3 trials, before progressing to 6 Phase 4 studies that continue to gather real-world data.
The focus broadened to include a wide array of conditions such as insomnia, Post Traumatic Stress Disorder (PTSD), sleep disorders, emotional processing, and cognitive functioning. More recent studies are exploring its role in menopausal insomnia, postoperative delirium, and even as a potential preventive measure for Alzheimer's disease, demonstrating the ongoing commitment to understanding the full therapeutic scope of daridorexant.