A Clinical Trial of Adjunctive and Monotherapy PRAX-114 in Participants With Major Depressive Disorder

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of 10, 20, 40 and 60 mg oral PRAX-114 compared to placebo in the treatment of adults with MDD. The study will enroll participants on adjunctive treatment who had an inadequate response to their current antidepressant treatment and participants not currently being treated with pharmacotherapy for MDD. A sub-study to investigate the pharmacokinetics (PK) of PRAX-114 and metabolites when dosed in the evening in participants with MDD will be conducted in a subset of participants at selected research sites with serial PK sampling capabilities.

Official Title
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A Phase 2 Double-blind, Placebo-Controlled, Dose-Ranging Clinical Trial to Evaluate the Efficacy and Safety of PRAX-114 in Adjunctive and Monotherapy Treatment of Participants With Major Depressive Disorder and Inadequate Response to Antidepressant Treatment

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: 10 mg PRAX-114
* Drug: 20 mg PRAX-114
* Drug: 40 mg PRAX-114
* Drug: 60 mg PRAX-114
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recurrent MDD diagnosis with a current episode duration of at least 12 weeks and no more than 24 months. HAM-D17 total score of ≥20 at Screening and Baseline Body mass index (BMI) between 18 and 38 kg/m2 (inclusive). Adjunctive treatment participants only: Inadequate response to treatment in the current MDD episode, defined as <50% reduction in depression severity in response to at least 1 and no more than 2 antidepressant trials at an adequate dose and duration in the current MDE as specified in the ATRQ. Adjunctive treatment participants only: Stable regimen of antidepressant treatment for at least 8 weeks prior to Baseline, with no clinically meaningful change (defined as no increase in dose and no decrease in dose ≥25% for tolerability) during that period. Exclusion Criteria: Lifetime history of seizures, including febrile seizures. Neurodegenerative disorder (eg, Alzheimer's disease, Parkinson's disease, multiple sclerosis, or Huntington's disease). 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. Any current psychiatric disorder (other than MDD). Lifetime history of treatment resistant depression. Received electroconvulsive therapy (ECT) or vagus nerve stimulation (VNS) within the last year or transcranial magnetic stimulation (TMS) within the last 6 months prior to Screening. 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: PRAX-114 (10 mg)<br>10 mg PRAX-114 once daily | Drug: 10 mg PRAX-114<br>* Once daily oral treatment<br>|
| Experimental: PRAX-114 (20 mg)<br>20 mg PRAX-114 once daily | Drug: 20 mg PRAX-114<br>* Once daily oral treatment<br>|
| Experimental: PRAX-114 (40 mg)<br>40 mg PRAX-114 once daily | Drug: 40 mg PRAX-114<br>* Once daily oral treatment<br>|
| Experimental: PRAX-114 (60 mg)<br>60 mg PRAX-114 once daily | Drug: 60 mg PRAX-114<br>* Once daily oral treatment<br>|
| Placebo Comparator: Placebo<br>Placebo once daily | Drug: Placebo<br>* Once daily oral treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in HAM-D17 total score at Day 15 | The HAM-D17 is a depression rating scale consisting of 17 items; 9 items are scored on a 5-point scale (ranging from 0 to 4), and 8 items are scored on a 3-point scale (ranging from 0 to 2). The total score of the 17 items ranges from 0 to 52 with higher scores indicating greater depression. Therefore, a decrease in the total score or on individual item scores indicates improvement. | 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in HAM-D17 total score at Day 29 | The HAM-D17 is a depression rating scale consisting of 17 items; 9 items are scored on a 5-point scale (ranging from 0 to 4), and 8 items are scored on a 3-point scale (ranging from 0 to 2). The total score of the 17 items ranges from 0 to 52 with higher scores indicating greater depression. Therefore, a decrease in the total score or on individual item scores indicates improvement. | 29 days | 
| Change from baseline in HAM-D17 total score at all other time points | The HAM-D17 is a depression rating scale consisting of 17 items; 9 items are scored on a 5-point scale (ranging from 0 to 4), and 8 items are scored on a 3-point scale (ranging from 0 to 2). The total score of the 17 items ranges from 0 to 52 with higher scores indicating greater depression. Therefore, a decrease in the total score or on individual item scores indicates improvement. | 4 days, 8 days, 22 days, 36 days, and 43 days | 
| Change from baseline in Clinical Global Impression-Severity (CGI-S) score at Day 15 and all other time points | 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). | 4 days, 8 days, 15 days, 22 days, 29 days, 36 days, and 43 days | 
| Clinical Global Impression-Improvement (CGI-I) score at Day 15 and all other time points | 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). | 4 days, 8 days, 15 days, 22 days, 29 days, 36 days, and 43 days | 
| HAM-D17 response (reduction from baseline score of ≥50%) at Day 15, Day 29, and all other time points | The HAM-D17 is a depression rating scale consisting of 17 items; 9 items are scored on a 5-point scale (ranging from 0 to 4), and 8 items are scored on a 3-point scale (ranging from 0 to 2). The total score of the 17 items ranges from 0 to 52 with higher scores indicating greater depression. Therefore, a decrease in the total score or on individual item scores indicates improvement. | 4 days, 8 days, 15 days, 22 days, 29 days, 36 days, and 43 days | 
| HAM-D17 remission (total score of ≤7) at Day 15, Day 29, and all other time points | The HAM-D17 is a depression rating scale consisting of 17 items; 9 items are scored on a 5-point scale (ranging from 0 to 4), and 8 items are scored on a 3-point scale (ranging from 0 to 2). The total score of the 17 items ranges from 0 to 52 with higher scores indicating greater depression. Therefore, a decrease in the total score or on individual item scores indicates improvement. | 4 days, 8 days, 15 days, 22 days, 29 days, 36 days, and 43 days | 
| Change from baseline in the Symptoms of Depression Questionnaire (SDQ) total and sub-scale scores at Day 15 and all other time points | The SDQ is a 44-item, self-report scale assessing the severity of symptoms across several subtypes of depression. Items are scored on a 7-point scale (ranging from 1 to 6). The SDQ total score is the sum of all 44 item scores and ranges from 44 to 264 with higher scores indicating worse symptoms. | 4 days, 8 days, 15 days, 22 days, 29 days, 36 days, and 43 days | 
| Patient Global Impression-Improvement (PGI-I) score at 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). | 4 days, 8 days, 15 days, 22 days, 29 days, 36 days, and 43 days | 
| Change from baseline in the Work and Social Adjustment Scale (WSAS) at Day 15 and all other time points | The WSAS assesses the degree to which mental health problems interfere with day-to-day functioning in 5 domains: work, social leisure activities, private leisure activities, home- management, and personal relationships. The WSAS total score is the sum of the 5 item scores and ranges from 0 to 40, with higher scores indicating poorer adjustment. | 4 days, 8 days, 15 days, 22 days, 29 days, 36 days, and 43 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mood Disorders, Depressive Disorder, Depression, Depressive Disorder, Unipolar, Depressive Symptoms, Agents, GABA, Receptors, GABA-A, Allosteric Regulation