Safety and Efficacy of NYX-783 in Subjects With Post-Traumatic Stress Disorder

Study Overview
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Brief Summary
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To evaluate the safety, tolerability, and response profile of NYX-783 in a Post-Traumatic Stress Disorder population.

Detailed Description
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The study will be a 10 to 12-week study, including a 1 to 3-week screening Period, followed by a double-blind, randomized, placebo-controlled, parallel-group Treatment Period, and a 1-week follow-up Period. Subjects eligible for the study will be randomized to receive either NYX-783 (4-weeks) or placebo (4 or 8-weeks).

Official Title
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A Study to Evaluate the Safety and Efficacy of NYX-783 in Subjects With Post-Traumatic Stress Disorder

Conditions
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Post-Traumatic Stress Disorder

Intervention / Treatment
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* Drug: Placebo oral capsule
* Drug: NYX-783


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A primary diagnosis of PTSD [Post Traumatic Stress Disorder, according to DSM-5 (Diagnostic and Statistical Manual of Mental Disorders)] with the primary traumatic event occurring ≥12 months prior to screening. PCL-5 (PTSD Checklist for DSM-5) ≥38 at screening. CAPS-5 (Clinician-Administered PTSD Scale for DSM-5) total score ≥30 at screening. Exclusion Criteria: Complex PTSD. Trauma focused psychotherapies. Primary traumatic event occurred prior to 2001. Primary traumatic event was followed by further major traumatic life episodes. Other psychiatric disorders that is the primary focus of treatment or followed/worsened since exposure to the trauma (except for major depressive disorder or anxiety disorders that followed exposure to the trauma or an anxiety disorder that showed a worsening after trauma) Current use of medications with primarily central nervous system activities Other clinically significant medical histories that may interfere with completing the study.

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
Interventional Model Description: Subjects will be randomized to receive placebo or NYX-783.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo oral capsule<br>* Matching placebo capsules.<br>|
| Experimental: NYX-783 Low Dose (10 mg QD)<br> | Drug: NYX-783<br>* NYX-783 is a small molecule that modulates the N-methyl-D-aspartate receptor (NMDAR).<br>|
| Experimental: NYX-783 High Dose (50 mg QD)<br> | Drug: NYX-783<br>* NYX-783 is a small molecule that modulates the N-methyl-D-aspartate receptor (NMDAR).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CAPS-5 [Clinician-Administered PTSD Scale for DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition)] Total Score and Subscores | CAPS-5 [Clinician Administered PTSD Scale for DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition)] is a structured interview for diagnosis and assessment of PTSD. The assessor combines information about frequency and intensity of an item into a severity rating (0-4). CAPS-5 total symptom severity score is calculated by summing severity scores for the 20 DSM-5 PTSD symptoms. CAPS-5 symptom cluster severity scores are calculated by summing the individual item severity scores for symptoms corresponding to a given DSM-5 cluster: intrusions (items 1-5, minimum score 0, maximum score 20), avoidance (items 6-7, minimum score 0, maximum score 8), negative alterations in cognitions and mood (items 8-14, minimum score 0, maximum score 28), and alterations in arousal and reactivity (items 15-20, minimum score 0, maximum score 24). CAPS-5 Total Scores range from 0 to 80. A higher score corresponds to more severe PTSD. | Change from baseline to week 4 (Stage 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PCL-5 (PTSD-Checklist for DSM-5) | Assess the effect of NYX-783 compared to placebo in changes of symptoms as measured by PCL-5. The PCL-5 ranges from 0 to 80; a higher score corresponds to more severe PTSD. | Change from baseline to week 4 (Stage 1) | 
| PSQI (Pittsburgh Sleep Quality Index) Global Score | Assess the effects of NYX-783 compared to placebo in changes in sleep quality as measure by the PSQI Global Score. The PSQI is a questionnaire to assess sleep quality and disturbances. In scoring the PSQI, seven component scores are derived, each scored 0 (no difficulty) to 3 (severe difficulty). The component scores are summed to produce a global score (range 0 to 21). Higher scores indicate worse sleep quality. A score >5 indicates significant sleep disturbance. | Change from baseline to week 4 (Stage 1) | 
| PSQI-A (Pittsburgh Sleep Quality Index-Addendum) Global Score | Assess the effects of NYX-783 compared to placebo in changes in sleep quality as measure by the PSQI-A Global Score. The PSQI-A score ranges from 0-21; lower scores represent less disruptive behavior. | Change from baseline to week 4 (Stage 1) | 
| BAC (Brief Assessment of Cognition) Symbol Coding | Assess the effect of NYX-783 compared to placebo in changes in cognitive function as measured by the BAC Symbol Coding. BAC symbol coding score is a count which ranges from 0 to 110; higher scores represent higher function. | Change from baseline to week 4 (Stage 1) | 
| CGI-S (Clinical Global Impression - Severity) | Assess the effect of NYX-783 compared to placebo in the change in global clinical severity of PTSD symptoms as measured by the CGI-S. The Clinical Global Impressions-Severity (CGI-S) score ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill subjects). | Change from baseline to week 4 (Stage 1) | 
| HADS-A (Hospital Anxiety and Depression Scale) | The HADS is a self-assessment tool consisting of two subscales, one for anxiety (HADS-A) and one for depression (HADS-D). Scores for items in each subscale of the HADS are summed to produce an anxiety score (HADS-A) or a Depression score (HADS-D), or can be added to produce a total score (HADS-T). Each item is rated on a 4-point scale (ranging from 0 = no not at all, to 3 = yes definitely), for a total score ranging from 0-42 and sub scores for anxiety or depression ranging from 0-21 for each subscale. Higher scores represent more severe anxiety or depression. HADS-A is presented here. | From baseline to week 4 (Stage 1) |