A Clinical Trial of PRAX-114 in Participants With Post-Traumatic Stress Disorder

Study Overview
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Brief Summary
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This trial is comprised of a 4-week randomized, double-blind, placebo-controlled treatment period followed by an optional 8-week open-label extension (OLE) period. This trial will evaluate the efficacy and safety of oral PRAX-114 flexibly dosed at 40 to 60 mg for 4 weeks compared to placebo in adults with PTSD. The OLE period consisting of treatment with 40 mg PRAX-114 for 8 weeks will provide additional efficacy and safety data.

Official Title
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A Phase 2, Randomized, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of PRAX-114 in Participants With Post-Traumatic Stress Disorder

Conditions
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Post-traumatic Stress Disorder, Post Traumatic Stress Disorder, Stress Disorder, Stress Disorders, Post-Traumatic, Trauma and Stressor Related Disorders, Mental Disorder

Intervention / Treatment
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* Drug: 60 mg PRAX-114 or 40 mg PRAX-114
* Drug: Placebo
* Drug: 40 mg PRAX-114


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: DSM-5 diagnosis of PTSD with duration >6 months, as confirmed by psychiatric evaluation. CAPS-5 total score ≥30 at Screening and Baseline. Body mass index (BMI) of 18 to 38 kg/m2. Exclusion Criteria: Experienced the index traumatic event before age 16. Has an active legal, worker's compensation, or disability claim for PTSD. Lifetime history of bipolar disorder, a psychotic disorder (eg, schizophrenia or schizoaffective disorder), or obsessive-compulsive disorder or a history of a psychotic mood episode in last 2 years. HAM-D17 score of >18 at Screening or Baseline. Any current psychiatric disorder (other than PTSD). Lifetime history of seizures, including febrile seizures. Daily consumption of more than 2 standard alcohol-containing beverages for males or more than 1 standard alcohol-containing beverages for females.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Double-blind PRAX-114<br>Double-blind period - 40 or 60 mg PRAX-114 once daily in the evening | Drug: 60 mg PRAX-114 or 40 mg PRAX-114<br>* Once daily oral treatment for 4 weeks<br>|
| Placebo Comparator: Double-blind Placebo<br>Double-blind period - placebo once daily in the evening | Drug: Placebo<br>* Once daily oral treatment for 4 weeks<br>|
| Experimental: Open-label Extension PRAX-114<br>Open-label extension period - 40 mg PRAX-114 once daily in the evening | Drug: 40 mg PRAX-114<br>* Once daily oral treatment for 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total score at Day 29 | The CAPS-5 is a clinician-rated PTSD rating scale consisting of 30 items; the total score is calculated as the sum of 20 items assessing the 20 DSM-5 PTSD symptoms. These symptom items are scored on a 5-point scale from 0 (absent) to 4 (extreme/incapacitating). The total score of the 20 items ranges from 0 to 80 with higher scores indicating more severe PTSD symptoms. Therefore, a decrease in the total score indicates symptom improvement. | 29 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the CAPS-5 total score at Day 15 and 43 | The CAPS-5 is a clinician-rated PTSD rating scale consisting of 30 items; the total score is calculated as the sum of 20 items assessing the 20 DSM-5 PTSD symptoms. These symptom items are scored on a 5-point scale from 0 (absent) to 4 (extreme/incapacitating). The total score of the 20 items ranges from 0 to 80 with higher scores indicating more severe PTSD symptoms. Therefore, a decrease in the total score indicates symptom improvement. | 15 days and 43 days | 
| Change from baseline in Clinical Global Impression-Severity (CGI-S) score at Day 29, Day 15, and Day 43 | The CGI-S assesses the clinician's impression of the participant's current depression symptoms. The clinician should use his/her total clinical experience with this patient population and rate the current severity of the participant's mental illness on a 7-point scale from 1 (Normal, not at all ill) to 7 (Among the most extremely ill patients). | 15 days, 29 days, and 43 days | 
| Change from baseline in Clinical Global Impression-Improvement (CGI-I) score at Day 29, Day 15, and Day 43 | The CGI-I assesses the participant's improvement (or worsening). The clinician is required to assess the participant's condition relative to Baseline (Day 1) on a 7-point scale from 1 (Very much improved) to 7 (Very much worse). | 15 days, 29 days, and 43 days | 
| Change from baseline in the CAPS-5 symptom cluster scores at Day 29, Day 15, and Day 43 | The CAPS-5 is a clinician-rated PTSD rating scale consisting of 30 items; 20 of these items assess the 20 DSM-5 PTSD symptoms. Symptom cluster scores are calculated as the sum of the individual item severity scores for symptoms contained in a given DSM-5 cluster. These symptom items are scored on a 5-point scale from 0 (absent) to 4 (extreme/incapacitating). Cluster score ranges vary by symptom cluster. Higher scores indicate more severe PTSD symptoms. Therefore, a decrease in the cluster score indicates symptom improvement. | 15 days, 29 days, and 43 days | 
| Change from baseline in the PTSD Checklist for DSM-5 (PCL-5) at Day 29, Day 15, and all other timepoints | The PCL-5 is a patient-reported PTSD rating scale consisting of 20 items; these items assess the 20 DSM-5 PTSD symptoms. These symptom items are scored on a 5-point scale from 0 (not at all) to 4 (extremely). The total score of the 20 items ranges from 0 to 80 with higher scores indicating more severe PTSD symptoms. Therefore, a decrease in the total score indicates symptom improvement. | 8 days, 15 days, 22 days, 29 days, 35 days, and 43 days | 
| Change from baseline in the Sheehan Disability Scale (SDS) at Day 29, Day 15, and Day 43 | The SDS is a patient-reported measure of disability. The SDS is a composite of 3 items designed to measure the extent to which 3 major domains in the patient's life are functionally impaired by psychiatric or medical symptoms: work, social life/leisure activities, and family life/home responsibilities. Each domain is rated on an 11-point scale from 0 (not at all) to 10 (extremely). The total score is calculated as the sum of the domain scores and ranges from 0 to 30. Higher scores indicate greater disability. Therefore, a decrease in the total score or on individual domains indicates less disability. | 15 days, 29 days, 43 days | 
| Patient Global Impression-Improvement (PGI-I) score at Day 29, Day 15 and all other time points | The PGI-I scale is a global self-assessment used to rate the response of a participant's condition to therapy or intervention. It consists of 1 question that asks the participant to rate their current condition compared to how it was prior to beginning treatment on a scale of 1 (very much better) to 7 (very much worse). | 8 days, 15 days, 22 days, 29 days, 35 days, and 43 days | 
| Change from baseline in the Insomnia Severity Index (ISI) at Day 29, Day 15, and all other timepoints | The ISI is a patient-reported measure of insomnia consisting of 7 items assessing the nature, severity, and impact of insomnia. These items are scored on a 5-point scale from 0 (no problem) to 4 (very severe problem). The total score ranges from 0 to 28 with higher scores indicating more severe insomnia. Therefore, a decrease in the total score indicates symptom improvement. | 8 days, 15 days, 22 days, 29 days, 35 days, and 43 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Agents, GABA, Receptors, GABA-A, Allosteric Regulation, PRAX-114