Daridorexant for PTSD
Recruiting in Palo Alto (17 mi)
+6 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Waitlist Available
Sponsor: Global Coalition for Adaptive Research
Prior Safety Data
Approved in 3 Jurisdictions
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.
12345What 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.
678910Eligibility 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.
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Intervention C DaridorexantExperimental Treatment1 Intervention
Group II: Intervention C PlaceboPlacebo Group1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Advanced Discovery ResearchAtlanta, GA
Upstate Clinical Research Associates, LLCWilliamsville, NY
Homestead Associates in Research, Inc.Miami, FL
Advanced Discovery ResearchDecatur, GA
More Trial Locations
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Who Is Running the Clinical Trial?
Global Coalition for Adaptive ResearchLead Sponsor
PPD DEVELOPMENT, LPIndustry Sponsor
CitelineIndustry Sponsor
U.S. Army Medical Research and Development CommandCollaborator
PPDIndustry Sponsor
Berry ConsultantsCollaborator
Idorsia Pharmaceuticals Ltd.Industry Sponsor
Cambridge Cognition LtdIndustry Sponsor
CitelineCollaborator
References
Quetiapine for treatment of refractory symptoms of combat-related post-traumatic stress disorder. [2017]To assess the effects of adjunctive quetiapine for treatment of refractory symptoms of combat-related post-traumatic stress disorder (PTSD), charts of Vietnam veterans with war-connected PTSD who had been prescribed quetiapine were reviewed. Only patients with symptoms that had not responded to adequate therapy with two or more psychotropic medications prior to quetiapine treatment were analyzed. Addition of quetiapine to ongoing therapy resulted in further symptomatic improvements in DSM-IV PTSD criterion B (re-experiencing) for 35%, criterion C (avoidance/numbing) for 28%, and criterion D (arousal) for 65% of study subjects. Low doses of quetiapine (mean = 155 +/- 130 mg) were associated with minimal side effects. These results, although retrospective, suggest that augmentative quetiapine may benefit some refractory symptoms of PTSD in combat veterans.
Quetiapine as an adjunctive treatment for post-traumatic stress disorder: an 8-week open-label study. [2022]This study evaluated the effectiveness of quetiapine for subjects with post-traumatic stress disorder (PTSD) who were already on a stable dose of a selective serotonin reuptake inhibitor (SSRI) but had significant PTSD symptoms. Fifteen subjects were enrolled in an 8-week open-label trial for PTSD in which quetiapine was added to an SSRI. Subjects were on a stable dose of the SSRI for at least 6 weeks before study entry and had a Clincian-Administered PTSD Scale (CAPS) score of greater than or equal to 50 at study baseline. The mean age of subjects was 49 years (eight men and seven women). The average duration of PTSD was 29 years, one-third of subjects had combat-related PTSD, and two-thirds had noncombat PTSD. The mean dose prescribed in the study was 216 mg per day. The initial median CAPS score was 80, indicating severe PTSD. The addition of a modest dose of quetiapine provided significant relief from PTSD symptoms with a 42% overall improvement in PTSD symptoms based on the CAPS and significant improvement along each dimension of symptoms: re-experiencing (Z=-3.24, P=0.0012), hyperarousal (Z=-3.30, P=0.001) and avoidance (Z=-2.13, P=0.03). Subjects rated themselves as 45% improved on average on the Davidson Trauma Scale and reported a 44% decrease in their level of disability and impairment as reflected by the Sheehan Disability Scale. Subjects with PTSD who had significant PTSD symptoms when on an SSRI benefited from the addition of quetiapine. Patients improved significantly on all three clusters of PTSD symptoms: re-experiencing, hyperarousal and avoidance.
Quetiapine treatment in patients with posttraumatic stress disorder: an open trial of adjunctive therapy. [2019]In this 6-week, open-label trial, combat veterans meeting DSM-IV criteria for posttraumatic stress disorder (PTSD) were treated with the atypical antipsychotic quetiapine. The starting dose was 25 mg at bedtime with subsequent titration based on tolerability and clinical response. Primary outcome was measured using the Clinician Administered PTSD Scale (CAPS). Secondary assessments of efficacy included the Positive and Negative Symptom Scale (PANSS), the Hamilton Rating Scale for Depression, and the Clinical Global Impression Scale. Safety and tolerability evaluations included neurologic ratings, vital signs, and assessment of treatment-emergent side effects. Eighteen of 20 patients enrolled in the study completed 6 weeks of open-label treatment. The dose range of quetiapine was 25 to 300 mg daily, with an average of 100+/-70 mg/d. There was significant improvement in CAPS scores, from 89.8+/-15.7 to 67.5+/-21.0 (t=4.863, df=18,
Treatment of posttraumatic stress disorder with nefazodone. [2019]Selective serotonin reuptake inhibitors are useful in the treatment of posttraumatic stress disorder (PTSD), but have a number of side-effects which limit their acceptability. A newer serotonergic compound, nefazodone, has a different side-effect profile, thus making it a potentially promising compound to study. Seventeen private practice patients with PTSD were treated with nefazodone up to 600 mg/day for a maximum total treatment period of 12 weeks. All subjects were civilians, and were monitored for efficacy and side-effects at weeks 1, 2, 4, 6, 8 and 12. Nefazodone was associated with statistically significant improvement in mean scores on all six rating scales used to assess change from baseline in PTSD symptoms. Additionally, statistically significant improvement from baseline were seen for the intrusive, avoidant/numbing, and hyperarousal clusters on a global PTSD scale. Early improvements in nightmares and general sleep disturbance were observed. Overall, there was a 43% response rate at endpoint, or 60% in treatment completers, by observer rating. Side-effects (assessed on the Medication Effects Scale) were generally benign. Nefazodone was associated with clinical improvement in this population, and now needs to be studied in double-blind, placebo controlled, protocols.
Effectiveness, Acceptability and Safety of Pharmaceutical Management for Combat-Related PTSD in Adults Based on Systematic Review of Twenty-Two Randomized Controlled Trials. [2022]Objective: This study assessed the efficacy, acceptability, and safety of pharmaceutical management for combat-related post-traumatic stress disorder (PTSD) to provide a clinical decision-making basis for clinicians. Method: A comprehensive search was conducted using Ovid MEDLINE, Ovid EMBASE, Cochrane Library, Scopus, ScienceDirect, and Web of Science for randomized controlled trails (RCTs), which reported pharmaceutical management and placobo for adults with combat-related PTSD, that were published until April 21, 2021. The effectiveness, acceptability, and adverse events (AEs), were designed as interested outcomes. The change in total symptoms of combat-related PTSD according to the clinician rating scale was defined as primary outcome, and the others were defined as secondary outcomes. Results: Twenty-two RCTs with 1,221 patients were involved. Compared with placebo, overall active comparators had statistical differences for all outcomes, including the change in total symptoms of combat-related PTSD [SMD = -0.36, 95%CI (-0.62,-0.09)], depression [SMD = -0.28, 95%CI (-0.45,-0.10)], anxiety [SMD = -0.44, 95%CI (-0.64,-0.23)], re-experience [SMD = -0.33, 95%CI (-0.52,-0.13)], avoidance [SMD = -0.24, 95%CI (-0.43,-0.05)], and hyper-arousal [SMD = -0.26, 95%CI (-0.48,-0.03)]. Compared with the placebo, in terms of acceptability, overall active comparators did not significantly decrease all-cause discontinuance rates [RR = 0.97, 95%CI (0.78,1.20)], and the significance decreased due to AEs [RR = 2.42, 95%CI (1.41,4.13)]. Nevertheless, overall there was no statistically significant difference for overall AEs, including somnolence, sedation, dizziness, paresthesia, anxiety, blurred vision, generalized anxiety disorder, and sleep disturbance. All funnel plots were symmetrical and no publication bias was found. Conclusion: Active drugs, especially amitriptyline, imipramine, and quetiapine, had a positive effect on the improvement of combat-related PTSD symptoms. Despite there being no significant increase in the AEs of the active drugs, the fact that the discontinuation rates of these drugs, including risperidone, imipramine, and topiramate, were increased deserves attention. Furthermore, as active drugs were effective across ethnic groups and battlefields, active drug regimens were revealed to be more appropriate for treating people with symptoms of extreme severe PTSD (≥80) or PTSD that is at least 8 weeks old. In addition, current evidence was from adults under 60 years of age and male combat-related PTSD. Whether this evidence can be extended to other populations of combat-related PTSD needs to be confirmed by subsequent high-quality, large-sample studies.
Spontaneous Reports of Serious Adverse Drug Reactions Resulting From Drug-Drug Interactions: An Analysis From the French Pharmacovigilance Database. [2021]Few data are available on the clinical impact of drug-drug interactions (DDIs). Most of the studies are limited to the analysis of exposure to potential DDI or the targeted impact of the combination of a few drugs or therapeutic classes. The analysis of adverse drug reaction (ADR) reports could be a mean to study generally the adverse effects identified due to a DDI. Our objective was to describe the characteristics of ADRs resulting from DDIs reported to the French Pharmacovigilance system and to identify the drugs most often implicated in these ADRs. Considering all ADR reports from January 01, 2012, to December 31, 2016, we identified all cases of ADR resulting from a DDI (DDI-ADRs). We then described these in terms of patients' characteristics, ADR seriousness, drugs involved (two or more per case), and ADR type. Of the 4,027 reports relating to DDI-ADRs, 3,303 were related to serious ADRs. Patients with serious DDI-ADRs had a median age of 76 years (interquartile range: 63-84); 53% were male. Of all serious DDI-ADRs, 11% were life-threatening and 8% fatal. In 36% of cases, the DDI causing the ADR involved at least three drugs. Overall, 8,424 different drugs were mentioned in the 3,303 serious DDI-ADRs considered. Altogether, drugs from the "antithrombotic agents" subgroup were incriminated in 34% of serious DDI-ADRs. Antidepressants were the second most represented therapeutic/pharmacological subgroup (5% of serious DDI-ADRs). Among the 3,843 ADR types reported in the 3,303 serious DDI-ADRs considered, the most frequently represented were hemorrhage (40% clinical hemorrhage; 6% biological hemorrhage), renal failure (8%), pharmacokinetic alteration (5%), and cardiac arrhythmias (4%). Hemorrhagic accidents are still an important part of serious ADRs resulting from DDIs reported in France. The other clinical consequences of DDIs seem less well identified by pharmacovigilance. Moreover, more than one-third of serious DDI-ADRs involved at least three drugs.
Acute fluvoxamine poisoning. [2017]A total of 221 cases of deliberate acute overdose with fluvoxamine reported to the Paris Poison Centre, and 78 cases collected by the International Drug Safety Department of Duphar BV were analysed. Other agents, mainly benzodiazepines, neuroleptics, other antidepressants and alcohol, were also taken in 77% of the cases. The acute toxicity that could be attributed to fluvoxamine alone was rarely severe. The symptoms observed were always benign when the dose of fluvoxamine was below 1000 mg and included drowsiness, tremor, nausea, vomiting, abdominal pain, bradycardia and/or anticholinergic effects (dry mouth, mydriasis, sinus tachycardia, urinary retention). Seizures occurred in a few cases after high doses (generally > 1500 mg). Cardiotoxicity was not a serious problem; sinus bradycardia was noted with doses of less than 1000 mg, but was always moderate and required no treatment. Conduction abnormalities were rare.
Pharmacovigilance of psychoactive medications in a Mexican psychiatric hospital. [2011]Pharmacovigilance is the permanent collection and assessment of the safety data of drugs in the interest of precise knowledge of the safety profile. We monitored notifications of suspected adverse reactions (AR) produced by psychoactive medications (ARPM) in a Psychiatry Hospital, during a 4-month period. Yellow cards for adverse reaction reporting were distributed to the medical personal at the Hospital Psiquiátrico Villa Ocaranza, Pachuca Hidalgo, Mexico. For each notification, the ARPM was analyzed in order to verify causality. One hundred twelve hospitalized patients entered the study (44 male and 68 female). The mean +/- SD age of the patients was 46 +/- 4.5 years. The major diagnoses found were: schizophrenia (35.7%), severe mental retardation (17 %), moderate mental retardation (MMR)/epilepsy (12.5%), MMR (8.03%), and others (26.7%). During the study there were 721 therapeutic regimens prescribed to patients on psychiatric service. Patients were receiving an average of 5.3 +/- 1.1 (range 4 to 8) psychiatric medications. The psychiatrists reported only 5 ARPMs in five patients (prevalence: 4.46%). Among the drugs involved were neuroleptics (47.8%), antiepileptic (39.1%), and others (13.04%). The organs and systems affected by the ARs were the central nervous system, skin, endocrinological and gastrointestinal. A causal association between the medication and the AR were classified as probable in three cases, as possible in one case, as doubtful in one case and as definite in no case.
Cutaneous adverse reactions to psychotropic drugs: data from a multicenter surveillance program. [2009]Cutaneous adverse drug reactions (CADRs) in psychiatric pharmacotherapy are common, potentially harmful, and among the most frequent types of adverse events. To date, most of the data regarding CADRs to psychotropic medications are anecdotal, and systematic studies are lacking, particularly with respect to modern "second-generation" drugs.
Identifying and Characterizing Serious Adverse Drug Reactions Associated With Drug-Drug Interactions in a Spontaneous Reporting Database. [2021]Background: Drug-drug interactions (DDIs) are an important cause of adverse drug reactions (ADRs). In literature most of studies focus only on potential DDIs, while detailed data on serious ADRs associated with DDIs are limited. Our aim is to identify and characterize serious ADRs caused by DDIs using a spontaneous reporting database. Methods: All serious ADR reports, not related to vaccines and with a "definite", "probable" or "possible" causality assessment, inserted into the National Pharmacovigilance database from Veneto Region (January 1, 2015 to May 31, 2020) were analyzed. A list of drug pairs was created by selecting the reports containing at least two suspected or concomitant drugs. We verified which drug pairs potentially interacted according to the online version of DRUGDEX® system. For each potential DDI we controlled whether the ADR description in the report corresponded to the interaction effect as described in Micromedex. A detailed characterization of all serious reports containing an occurring DDI was performed. Results: In the study period a total of 31,604 reports of suspected ADRs from the Veneto Region were identified, of which 2,195 serious reports (6.9% of all ADR reports) containing at least two suspected or concomitant drugs were analyzed. We identified 1,208 ADR reports with at least one potential DDI (55.0% of 2,195) and 381 reports (17.4% of 2,195 reports) with an occurring ADR associated with a DDI. The median age of patients and the number of contraindicated or major DDIs were significantly higher in reports with an occurring DDI. Warfarin was the most frequently reported interacting drug and the most common ADRs were gastrointestinal or cerebral hemorrhagic events. The proton pump inhibitors/warfarin, followed by platelet aggregation inhibitors/warfarin were the drug-drug combinations most frequently involved in ADRs caused by DDIs. The highest proportion of fatal reports was observed with platelet aggregation inhibitors/warfarin and antidepressants/warfarin. Conclusion: Our findings showed that about one-third of patients exposed to a potential DDI actually experienced a serious ADR. Furthermore, our study confirms that a spontaneous reporting database could be a valuable resource for identifying and characterizing ADRs caused by DDIs and the drugs leading to serious ADRs and deaths.
Quetiapine Treatment for Post-traumatic Stress Disorder: A Systematic Review of the Literature. [2023]Paroxetine and Sertraline are the only medications approved in posttraumatic stress disorder (PTSD). However, about 60% of traumatized patients fail to show an adequate clinical response. Second generation antipsychotics are recommended as second-line monotherapy or third-line augmentation strategies and quetiapine appears as one of the most used and promising agents. Up to date, no reviews assessed the efficacy of quetiapine in the treatment of PTSD. We aimed to assess the effectiveness and general safety of quetiapine on PTSD. A systematic review was conducted following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and Cochrane guidelines, selecting studies that evaluated the efficacy of quetiapine on global or specific PTSD symptomatology. Ten studies (n = 894) were considered eligible for qualitative synthesis: one case report, one case series, one prospective cohort study, 3 open-label trials, 3 retrospective studies, one randomized controlled trial. Quetiapine was effective on global PTSD symptomatology assessed in 6 studies as well as on re-experiencing (4/4 studies), avoidance (4/3 studies) and hyperarousal (4/4 studies), flashbacks (2/2 studies), depressive (4/4 studies), anxiety (1/1 studies), psychotic (3/3 studies), insomnia (4/5 studies), nightmares (3/3 studies) specific symptoms and PTSD domains. Sedation was among the most frequently observed adverse effects and the main cause of drug discontinuation. Preliminary findings support the efficacy of quetiapine in ameliorating symptoms relative to PTSD and its overall safety. However, quetiapine use in PTSD cannot be recommended yet as studies mainly rely on open-label, retrospective studies or case series.
Treatment of Post-Traumatic Stress Disorder Nightmares at a Veterans Affairs Medical Center. [2020]The effectiveness of medications for PTSD in general has been well studied, but the effectiveness of medicatio.ns prescribed specifically for post-traumatic stress disorder (PTSD) nightmares is less well known. This retrospective chart review examined the efficacy of various medications used in actual treatment of PTSD nightmares at one Veteran Affairs Hospital. Records at the Salem, VA Veterans Affairs Medical Center (VAMC) were examined from 2009 to 2013 to check for the efficacy of actual treatments used in comparis.on with treatments suggested in three main review articles. The final sample consisted of 327 patients and 478 separate medication trials involving 21 individual medications plus 13 different medication combinations. The three most frequently utilized medications were prazosin (107 trials), risperidone (81 trials), and quetiapine (72 trials). Five medications had 20 or more trials with successful results (partial to full nightmare cessation) in >50% of trials: risperidone (77%, 1.0-6.0 mg), clonidine (63%, 0.1-2.0 mg), quetiapine (50%, 12.5-800.0 mg), mirtazapine (50%; 7.5-30.0 mg), and terazosin (64%, 50.0-300.0 mg). Notably, olanzapine (2.5-10.0) was successful (full remission) in all five prescription trials in five separate patients. Based on the clinical results, the use of risperidone, clonidine, terazosin, and olanzapine warrants additional investigation in clinically controlled trials as medications prescribed specifically for PTSD nightmares.