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
Overview
- Phase
- Phase 2
- Intervention
- 60 mg PRAX-114
- Conditions
- Major Depressive Disorder
- Sponsor
- Praxis Precision Medicines
- Enrollment
- 110
- Locations
- 1
- Primary Endpoint
- Change from baseline in HAM-D17 total score at Day 15
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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.
Arms & Interventions
PRAX-114 (60 mg)
60 mg PRAX-114 once daily
Intervention: 60 mg PRAX-114
PRAX-114 (10 mg)
10 mg PRAX-114 once daily
Intervention: 10 mg PRAX-114
PRAX-114 (20 mg)
20 mg PRAX-114 once daily
Intervention: 20 mg PRAX-114
PRAX-114 (40 mg)
40 mg PRAX-114 once daily
Intervention: 40 mg PRAX-114
Placebo
Placebo once daily
Intervention: Placebo
Outcomes
Primary Outcomes
Change from baseline in HAM-D17 total score at Day 15
Time Frame: 15 days
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.
Secondary Outcomes
- Change from baseline in Clinical Global Impression-Severity (CGI-S) score at Day 15 and all other time points(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(4 days, 8 days, 15 days, 22 days, 29 days, 36 days, and 43 days)
- Change from baseline in HAM-D17 total score at Day 29(29 days)
- Change from baseline in HAM-D17 total score at all other time points(4 days, 8 days, 22 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(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(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(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(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(4 days, 8 days, 15 days, 22 days, 29 days, 36 days, and 43 days)