Daridorexant for PTSD

Recruiting at 10 trial locations

Overseen By Please visit the website:

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Global Coalition for Adaptive Research

Must not be taking: Daridorexant

Disqualifiers: Narcolepsy, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called daridorexant to determine its effectiveness in helping people with PTSD (post-traumatic stress disorder). The goal is to assess the safety and efficacy of daridorexant in reducing PTSD symptoms. Participants will receive either the medication or a placebo (a pill with no active ingredients) to compare outcomes. People with PTSD who have never used daridorexant and have no history of narcolepsy might be suitable candidates for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Do I have to stop taking my current medications for this trial?

The trial information does not specify if you need to stop taking your current medications. Please refer to the Master Protocol (NCT05422612) for more details.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please refer to the Master Protocol (NCT05422612) for more details or consult with the trial coordinators.

Is there any evidence suggesting that daridorexant is likely to be safe for humans?

Research shows that daridorexant, a medication approved for treating insomnia, has been studied for its safety in people. In past studies on insomnia, most participants tolerated daridorexant well. The side effects were usually mild or moderate, with some experiencing headaches or drowsiness.

Specific safety information for daridorexant in people with PTSD is not yet available, but its approval for another condition provides insight into its safety profile. This suggests that while some side effects might occur, they are likely manageable and not severe for most individuals.

Prospective trial participants might find this information reassuring. However, discussing any concerns with the trial team is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Daridorexant is unique because it targets the orexin system, which is different from most current PTSD treatments that primarily focus on serotonin or norepinephrine pathways. This approach could offer new hope for patients by potentially reducing hyperarousal and sleep disturbances, common symptoms in PTSD, with a different mechanism of action. Researchers are excited about daridorexant because it could provide an alternative for those who don't respond well to existing medications like SSRIs or SNRIs, offering a fresh avenue for managing symptoms more effectively.

What evidence suggests that daridorexant might be an effective treatment for PTSD?

Research has shown that daridorexant can improve sleep, offering promise for treating PTSD. An early report found that patients taking daridorexant experienced better sleep, which may help alleviate PTSD symptoms. This trial will compare daridorexant to a placebo to assess its effectiveness in enhancing sleep and potentially reducing PTSD symptoms. The medication is already approved for treating sleep problems in adults, demonstrating its efficacy for sleep issues. Animal studies suggest that daridorexant might also reduce fear and stress, common in PTSD. These findings indicate that daridorexant could benefit people with PTSD by improving sleep and reducing stress. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for individuals with PTSD who meet the criteria outlined in the Master Protocol (NCT05422612). People cannot participate if they have a history of narcolepsy or previous treatment with daridorexant.

Inclusion Criteria

No additional inclusion criteria beyond the inclusion criteria specified in the Master Protocol (NCT05422612)

Exclusion Criteria

History of narcolepsy

I have never been treated with daridorexant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive either daridorexant or placebo for the treatment of PTSD

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Daridorexant

Trial Overview

The study is testing Daridorexant, a potential medication for PTSD, against a placebo. Participants will be randomly assigned to receive either Daridorexant or an inactive substance without knowing which one they are getting.

How Is the Trial Designed?

Group I: Intervention C Daridorexant Experimental Treatment 1 Intervention

Group II: Intervention C Placebo Placebo Group 1 Intervention

Daridorexant is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Quviviq for:

• Insomnia

Approved in European Union as Quviviq for:

• Insomnia

Approved in Canada as Quviviq for:

• Insomnia

Who Is Running the Clinical Trial?

Global Coalition for Adaptive Research

Lead Sponsor

Trials

7

Recruited

22,600+

PPD DEVELOPMENT, LP

Industry Sponsor

Trials

167

Recruited

38,000+

David Simmons

PPD DEVELOPMENT, LP

Chief Executive Officer since 2012

BSc in Applied Science from Georgia Institute of Technology

Martina Flammer

PPD DEVELOPMENT, LP

Chief Medical Officer since 2024

MD

Citeline

Industry Sponsor

Trials

5

Recruited

1,600+

PPD Development, LP

Industry Sponsor

U.S. Army Medical Research and Development Command

Collaborator

Trials

296

Recruited

249,000+

PPD

Industry Sponsor

Trials

162

Recruited

36,600+

Dr. Austin Smith

PPD

Chief Medical Officer since 2020

Doctor of Medicine from the Royal College of Surgeons in Ireland

David Simmons

PPD

Chief Executive Officer since 2012

Bachelor’s degree in Applied Mathematics and Industrial Management from Carnegie Mellon University

Berry Consultants

Collaborator

Trials

16

Recruited

58,200+

Idorsia Pharmaceuticals Ltd.

Industry Sponsor

Trials

124

Recruited

36,400+

Antonio Olivieri

Idorsia Pharmaceuticals Ltd.

Chief Medical Officer since 2024

Not specified

André C. Muller

Idorsia Pharmaceuticals Ltd.

Chief Executive Officer

Not specified

Cambridge Cognition Ltd

Industry Sponsor

Trials

17

Recruited

4,700+

Citeline

Collaborator

Trials

5

Recruited

1,600+

Published Research Related to This Trial

Quetiapine has shown effectiveness in reducing various PTSD symptoms, including re-experiencing, avoidance, hyperarousal, and insomnia, based on a systematic review of 10 studies involving 894 participants.

Despite its promising efficacy, quetiapine's use in PTSD treatment cannot be fully recommended yet due to the reliance on less rigorous study designs like open-label trials and case series, with sedation being a common side effect leading to discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quetiapine Treatment for Post-traumatic Stress Disorder: A Systematic Review of the Literature. Crapanzano, C., Damiani, S., Casolaro, I., et al.[2023]

A study of 4,027 adverse drug reaction reports from the French Pharmacovigilance system revealed that 3,303 were serious and often involved multiple drugs, with 36% of cases linked to at least three medications.

Antithrombotic agents were implicated in 34% of serious drug-drug interaction-related adverse reactions, with hemorrhages being the most common type of serious adverse effect, highlighting the need for careful monitoring of drug combinations, especially in older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spontaneous Reports of Serious Adverse Drug Reactions Resulting From Drug-Drug Interactions: An Analysis From the French Pharmacovigilance Database. Létinier, L., Ferreira, A., Marceron, A., et al.[2021]

In a review of Vietnam veterans with combat-related PTSD who had not responded to previous treatments, adding quetiapine led to significant improvements in PTSD symptoms: 35% in re-experiencing, 28% in avoidance/numbing, and 65% in arousal.

Quetiapine was administered at low doses (average 155 mg) and was associated with minimal side effects, suggesting it may be a safe adjunctive treatment for refractory PTSD symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quetiapine for treatment of refractory symptoms of combat-related post-traumatic stress disorder. Sokolski, KN., Denson, TF., Lee, RT., et al.[2017]

A study of 327 patients at a Veterans Affairs Hospital found that medications like risperidone, clonidine, and terazosin were effective in reducing PTSD nightmares, with risperidone showing success in 77% of trials.

The findings suggest that risperidone, clonidine, terazosin, and olanzapine should be further investigated in controlled trials for their potential as effective treatments specifically for PTSD nightmares.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Post-Traumatic Stress Disorder Nightmares at a Veterans Affairs Medical Center. Detweiler, MB., Pagadala, B., Candelario, J., et al.[2020]

In a study of 299 cases of fluvoxamine overdose, the acute toxicity was generally mild, with severe symptoms being rare, especially when doses were below 1000 mg.

Common symptoms included drowsiness, tremor, and nausea, while serious complications like seizures were only observed at doses over 1500 mg, indicating that fluvoxamine has a relatively safe profile in acute overdose situations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute fluvoxamine poisoning. Garnier, R., Azoyan, P., Chataigner, D., et al.[2017]

In a study of 17 patients with PTSD treated with nefazodone for up to 12 weeks, significant improvements were observed in PTSD symptoms across all six rating scales, indicating its potential efficacy as a treatment.

Nefazodone demonstrated a 43% response rate overall, with side effects being generally mild, suggesting it may be a safer alternative to traditional selective serotonin reuptake inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of posttraumatic stress disorder with nefazodone. Davidson, JR., Weisler, RH., Malik, ML., et al.[2019]

Pharmaceutical treatments, particularly amitriptyline, imipramine, and quetiapine, significantly improve symptoms of combat-related PTSD compared to placebo, with a moderate effect size across various PTSD symptoms.

While there was no significant increase in overall adverse events from these medications, higher discontinuation rates due to adverse effects were noted, indicating the need for careful monitoring in patients, especially those with severe PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness, Acceptability and Safety of Pharmaceutical Management for Combat-Related PTSD in Adults Based on Systematic Review of Twenty-Two Randomized Controlled Trials. Yan, JZ., Liu, JL., Li, XZ., et al.[2022]

In a 6-week open-label trial involving 20 combat veterans with PTSD, quetiapine significantly reduced PTSD symptoms, as measured by the Clinician Administered PTSD Scale (CAPS), with scores improving from 89.8 to 67.5.

The treatment was well tolerated, with no serious adverse events reported, suggesting that quetiapine may be a safe option for patients who have not responded adequately to other medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quetiapine treatment in patients with posttraumatic stress disorder: an open trial of adjunctive therapy. Hamner, MB., Deitsch, SE., Brodrick, PS., et al.[2019]

In a 4-month study involving 112 hospitalized psychiatric patients, only 5 adverse reactions to psychoactive medications were reported, indicating a low prevalence of 4.46% among patients receiving an average of 5.3 psychiatric medications.

The majority of reported adverse reactions were linked to neuroleptics and antiepileptic drugs, with the central nervous system being the most affected organ system, highlighting the need for ongoing monitoring of medication safety in psychiatric care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacovigilance of psychoactive medications in a Mexican psychiatric hospital. Ortiz, MI., Ponce-Monter, HA., Fernández-Martínez, E., et al.[2011]

In a study of 208,401 psychiatric inpatients, cutaneous adverse drug reactions (CADRs) were found in 0.1% of cases, with a notable risk associated with mood-stabilizing antiepileptic drugs, particularly lamotrigine and carbamazepine.

Modern second-generation antidepressants, such as selective serotonin reuptake inhibitors, showed a significantly lower incidence of CADRs compared to older tricyclic and tetracyclic antidepressants, indicating a safer profile for these newer medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cutaneous adverse reactions to psychotropic drugs: data from a multicenter surveillance program. Lange-Asschenfeldt, C., Grohmann, R., Lange-Asschenfeldt, B., et al.[2009]

In a study of 15 subjects with PTSD who were already on a stable SSRI dose, the addition of quetiapine for 8 weeks led to a significant 42% overall improvement in PTSD symptoms, as measured by the Clinician-Administered PTSD Scale (CAPS).

Participants experienced notable reductions in all three symptom clusters of PTSD: re-experiencing, hyperarousal, and avoidance, indicating that quetiapine can effectively enhance treatment outcomes for patients with persistent PTSD symptoms despite SSRI therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quetiapine as an adjunctive treatment for post-traumatic stress disorder: an 8-week open-label study. Ahearn, EP., Mussey, M., Johnson, C., et al.[2022]

Out of 2,195 serious adverse drug reaction (ADR) reports analyzed, 381 (17.4%) were linked to actual drug-drug interactions (DDIs), indicating that about one-third of patients with potential DDIs experienced serious ADRs.

Warfarin was frequently involved in these interactions, with the most common serious ADRs being gastrointestinal or cerebral hemorrhagic events, particularly with combinations like proton pump inhibitors/warfarin and platelet aggregation inhibitors/warfarin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identifying and Characterizing Serious Adverse Drug Reactions Associated With Drug-Drug Interactions in a Spontaneous Reporting Database. Magro, L., Arzenton, E., Leone, R., et al.[2021]

Citations

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clinicaltrials.gov

clinicaltrials.gov/study/NCT05948540

Department of Defense PTSD Adaptive Platform Trial

This is a Phase 2 randomized, double-blinded, placebo-controlled study that will evaluate multiple potential pharmacotherapeutic interventions for PTSD ...

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11946062/

A Preliminary Report on the Effects of Daridorexant in Patients ...

Results. All sleep outcomes significantly improved throughout treatment, which was generally safe and well tolerated, with mild and transient ...

3.

idorsia.us

idorsia.us/dam/jcr:03e8cbdd-be00-4b12-970d-6e025c5f4942/2023-dod-ptsd-study_final.pdf

Media Release May 10, 2023

This clinical trial will include. QUVIVIQ® (daridorexant) CIV, a medicine approved by the FDA for the treatment of adults with difficulty ...

4.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/nda/2022/214985Orig1s000IntegratedR.pdf

214985Orig1s000 - accessdata.fda.gov

PTSD post-traumatic stress disorder. PXR pregnane X receptor. QD once daily. REM rapid eye movement. SAD single-ascending dose. SAE serious ...

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sciencedirect.com

sciencedirect.com/science/article/pii/S2772408524001212

Anxiolytic-like effects of the dual orexin receptor antagonist ...

We conclude that daridorexant rather attenuated and did not intensify fear/stress responses in rats. It was effective in models that simulate endophenotypes ...

6.

withpower.com

withpower.com/trial/phase-2-stress-disorders-traumatic-6-2023-25971

Daridorexant for PTSD · Recruiting Participants for Phase ...

The provided research does not contain specific safety data for Daridorexant (also known as Quviviq, Nemorexant, ACT-541468, Daridorexant hydrochloride) in ...

7.

clinicaltrialsarena.com

clinicaltrialsarena.com/news/idorsia-pharmaceuticals-ptsd-quviviq/

Idorsia joins platform trial recruiting US veterans with PTSD

The study will investigate Quviviq alongside two FDA-approved drugs for the treatment for depression fluoxetine and vilazodone hydrochloride.

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12244194/

Anxiolytic-like effects of the dual orexin receptor antagonist ...

We conclude that daridorexant rather attenuated and did not intensify fear/stress responses in rats. It was effective in models that simulate endophenotypes ...

9.

en.wikipedia.org

en.wikipedia.org/wiki/Daridorexant

Daridorexant

"Safety and efficacy of daridorexant in patients with insomnia disorder: results from two multicentre, randomised, double-blind, placebo-controlled, phase 3 ...