Daridorexant for PTSD

Recruiting at 6 trial locations

Overseen By Please visit the website:

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Global Coalition for Adaptive Research

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: 0

200 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase 2 randomized, double-blinded, placebo-controlled study that will evaluate multiple potential pharmacotherapeutic interventions for PTSD utilizing an adaptive platform trial design. Intervention C - Daridorexant will assess the safety and efficacy of daridorexant in participants with PTSD. Please see NCT05422612 for information on the S-21-02 Master Protocol.

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.

What data supports the idea that Daridorexant for PTSD is an effective treatment?

The available research does not provide specific data on Daridorexant for PTSD. Instead, it discusses other drugs like quetiapine and nefazodone, which have shown improvements in PTSD symptoms. For example, quetiapine, when added to existing treatments, resulted in significant symptom relief, with a 42% overall improvement in PTSD symptoms. Nefazodone also showed clinical improvement with a 43% response rate. However, there is no direct evidence from the provided information about Daridorexant's effectiveness for PTSD. ^{1 2 3 4 5}

What safety data exists for Daridorexant in treating PTSD?

The provided research does not contain specific safety data for Daridorexant (also known as Quviviq, Nemorexant, ACT-541468, Daridorexant hydrochloride) in the treatment of PTSD. The studies focus on drug-drug interactions and adverse reactions related to other medications, but do not mention Daridorexant or its safety profile. ^{6 7 8 9 10}

Is the drug Daridorexant a promising treatment for PTSD?

The information provided does not include any studies or data about Daridorexant for treating PTSD, so we cannot determine if it is a promising treatment based on this information. ^{1 2 4 11 12}

Eligibility Criteria

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.

Treatment Details

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.

Participant Groups

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+

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+

Findings from Research

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]

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]

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 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]

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 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 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]

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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Quetiapine for treatment of refractory symptoms of combat-related post-traumatic stress disorder. [2017]

2. England pubmed.ncbi.nlm.nih.gov

Quetiapine as an adjunctive treatment for post-traumatic stress disorder: an 8-week open-label study. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Quetiapine treatment in patients with posttraumatic stress disorder: an open trial of adjunctive therapy. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Treatment of posttraumatic stress disorder with nefazodone. [2019]

5. Switzerland 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. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Spontaneous Reports of Serious Adverse Drug Reactions Resulting From Drug-Drug Interactions: An Analysis From the French Pharmacovigilance Database. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Acute fluvoxamine poisoning. [2017]

8. United States pubmed.ncbi.nlm.nih.gov

Pharmacovigilance of psychoactive medications in a Mexican psychiatric hospital. [2011]

9. United States pubmed.ncbi.nlm.nih.gov

Cutaneous adverse reactions to psychotropic drugs: data from a multicenter surveillance program. [2009]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Identifying and Characterizing Serious Adverse Drug Reactions Associated With Drug-Drug Interactions in a Spontaneous Reporting Database. [2021]

11. Korea (South) pubmed.ncbi.nlm.nih.gov

Quetiapine Treatment for Post-traumatic Stress Disorder: A Systematic Review of the Literature. [2023]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Treatment of Post-Traumatic Stress Disorder Nightmares at a Veterans Affairs Medical Center. [2020]