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

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

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.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Placebo; Drug: 10 mg PRAX-114; Drug: 20 mg PRAX-114; Drug: 40 mg PRAX-114; Drug: 60 mg PRAX-114

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Noble Park, Victoria, Australia, 3174
      • Praxis Research Site
• United States
  • California
    • Lafayette, California, United States, 94549
      • Praxis Research Site
    • Lemon Grove, California, United States, 91945
      • Praxis Research Site
    • Oceanside, California, United States, 92056
      • Praxis Research Site
    • Redlands, California, United States, 92374
      • Praxis Research Site
  • Florida
    • Jacksonville, Florida, United States, 32256
      • Praxis Research Site
    • Orange City, Florida, United States, 32763
      • Praxis Research Site
    • Orlando, Florida, United States, 32801
      • Praxis Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • Praxis Research Site
    • Decatur, Georgia, United States, 30030
      • Praxis Research Site
  • Maryland
    • Gaithersburg, Maryland, United States, 20877
      • Praxis Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Praxis Research Site
    • Worcester, Massachusetts, United States, 01655
      • Praxis Research Site
  • Missouri
    • O'Fallon, Missouri, United States, 63368
      • Praxis Research Site
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • Praxis Research Site
  • New York
    • Cedarhurst, New York, United States, 11516
      • Praxis Research Site
    • Rochester, New York, United States, 14618
      • Praxis Research Site
  • Ohio
    • Dayton, Ohio, United States, 45417
      • Praxis Research Site
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18104
      • Praxis Research Site
    • Media, Pennsylvania, United States, 19063
      • Praxis Research Site
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Praxis Research Site
  • Texas
    • Austin, Texas, United States, 78737
      • Praxis Research Site
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Praxis Research Site
  • Washington
    • Everett, Washington, United States, 98201
      • Praxis Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Recurrent MDD diagnosis with a current episode duration of at least 12 weeks and no more than 24 months.
2. HAM-D17 total score of ≥20 at Screening and Baseline
3. Body mass index (BMI) between 18 and 38 kg/m2 (inclusive).
4. 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.
5. 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:

1. Lifetime history of seizures, including febrile seizures.
2. Neurodegenerative disorder (eg, Alzheimer's disease, Parkinson's disease, multiple sclerosis, or Huntington's disease).
3. 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.
4. Any current psychiatric disorder (other than MDD).
5. Lifetime history of treatment resistant depression.
6. 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.
7. Daily consumption of more than 2 standard alcohol-containing beverages for males or more than 1 standard alcohol-containing beverages for females.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo once daily	Drug: Placebo; Once daily oral treatment
Experimental: PRAX-114 (10 mg); 10 mg PRAX-114 once daily	Drug: 10 mg PRAX-114; Once daily oral treatment
Experimental: PRAX-114 (20 mg); 20 mg PRAX-114 once daily	Drug: 20 mg PRAX-114; Once daily oral treatment
Experimental: PRAX-114 (40 mg); 40 mg PRAX-114 once daily	Drug: 40 mg PRAX-114; Once daily oral treatment
Experimental: PRAX-114 (60 mg); 60 mg PRAX-114 once daily	Drug: 60 mg PRAX-114; Once daily oral treatment

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of Adverse Events (AE)	An AE is any untoward medical occurrence in a clinical trial participant, temporally associated with the use of study drug, whether or not considered related to the study drug.	43 days
Incidence of AEs by preferred term	The incidence of AEs will be reported by preferred term, including any terms related to clinically significant changes in body temperature, pulse rate, respiratory rate, blood pressure (systolic and diastolic), clinical laboratory measures (chemistry, hematology, urinalysis, and coagulation), and electrocardiogram parameters (heart rate, PR, QRS, QT, and corrected QT intervals).	43 days
Incidence of Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicidal ideation or behavior	The C-SSRS is composed of 5 yes/no questions addressing suicidal behavior and 5 yes/no questions addressing suicidal ideation, with sub-questions assessing the severity. Incidence is measured as the number of "yes" answers indicating the presence of suicidal ideation or behavior.	43 days

Collaborators and Investigators

• Sponsor: Praxis Precision Medicines
• Investigators: Study Director: Executive Director Clinical Development, Praxis Precision Mediciines

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2021
• Primary Completion (Actual): July 15, 2022
• Study Completion (Actual): August 2, 2022

Study Registration Dates

• First Submitted: July 8, 2021
• First Submitted That Met QC Criteria: July 8, 2021
• First Posted (Actual): July 20, 2021

Study Record Updates

• Last Update Posted (Actual): August 19, 2022
• Last Update Submitted That Met QC Criteria: August 18, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Depression; Mood Disorders; Depressive Disorder; Depressive Symptoms; Agents, GABA; Receptors, GABA-A; Allosteric Regulation; Depressive Disorder, Unipolar
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Mood Disorders; Depression; Depressive Disorder; Disease; Depressive Disorder, Major; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Pramoxine
• Other Study ID Numbers: PRAX-114-214

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No