Clinical trial NCT04969510: A Clinical Trial of Adjunctive and Monotherapy PRAX-114 in Participants With Major Depressive Disorder
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Major Depressive Disorder
Keywords: Mood Disorders
Depressive Disorder
Depression
Depressive Disorder, Unipolar
Depressive Symptoms
Agents, GABA
Receptors, GABA-A
Allosteric Regulation
Lead sponsor: Praxis Precision Medicines
Sponsor class: INDUSTRY
First posted: 2021-07-20
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change from baseline in HAM-D17 total score at Day 15
timeFrame: 15 days
Secondary outcomes:
measure: Change from baseline in HAM-D17 total score at Day 29
timeFrame: 29 days
measure: Change from baseline in HAM-D17 total score at all other time points
timeFrame: 4 days, 8 days, 22 days, 36 days, and 43 days
measure: Change from baseline in Clinical Global Impression-Severity (CGI-S) score at Day 15 and all other time points
timeFrame: 4 days, 8 days, 15 days, 22 days, 29 days, 36 days, and 43 days
measure: Clinical Global Impression-Improvement (CGI-I) score at Day 15 and all other time points
timeFrame: 4 days, 8 days, 15 days, 22 days, 29 days, 36 days, and 43 days
measure: HAM-D17 response (reduction from baseline score of ≥50%) at Day 15, Day 29, and all other time points
timeFrame: 4 days, 8 days, 15 days, 22 days, 29 days, 36 days, and 43 days
measure: HAM-D17 remission (total score of ≤7) at Day 15, Day 29, and all other time points
timeFrame: 4 days, 8 days, 15 days, 22 days, 29 days, 36 days, and 43 days
measure: Change from baseline in the Symptoms of Depression Questionnaire (SDQ) total and sub-scale scores at Day 15 and all other time points
timeFrame: 4 days, 8 days, 15 days, 22 days, 29 days, 36 days, and 43 days
measure: Patient Global Impression-Improvement (PGI-I) score at Day 15 and all other time points
timeFrame: 4 days, 8 days, 15 days, 22 days, 29 days, 36 days, and 43 days
measure: Change from baseline in the Work and Social Adjustment Scale (WSAS) at Day 15 and all other time points
timeFrame: 4 days, 8 days, 15 days, 22 days, 29 days, 36 days, and 43 days
Other outcomes:
measure: Incidence and severity of Adverse Events (AE)
timeFrame: 43 days
measure: Incidence of AEs by preferred term
timeFrame: 43 days
measure: Incidence of Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicidal ideation or behavior
timeFrame: 43 days
Locations:
city: Lafayette
country: United States
facility: Praxis Research Site
state: California
city: Lemon Grove
country: United States
facility: Praxis Research Site
state: California
city: Oceanside
country: United States
facility: Praxis Research Site
state: California
city: Redlands
country: United States
facility: Praxis Research Site
state: California
city: Jacksonville
country: United States
facility: Praxis Research Site
state: Florida
city: Orange City
country: United States
facility: Praxis Research Site
state: Florida
city: Orlando
country: United States
facility: Praxis Research Site
state: Florida
city: Atlanta
country: United States
facility: Praxis Research Site
state: Georgia
city: Decatur
country: United States
facility: Praxis Research Site
state: Georgia
city: Gaithersburg
country: United States
facility: Praxis Research Site
state: Maryland
city: Boston
country: United States
facility: Praxis Research Site
state: Massachusetts
city: Worcester
country: United States
facility: Praxis Research Site
state: Massachusetts
city: O'Fallon
country: United States
facility: Praxis Research Site
state: Missouri
city: Las Vegas
country: United States
facility: Praxis Research Site
state: Nevada
city: Cedarhurst
country: United States
facility: Praxis Research Site
state: New York
city: Rochester
country: United States
facility: Praxis Research Site
state: New York
city: Dayton
country: United States
facility: Praxis Research Site
state: Ohio
city: Allentown
country: United States
facility: Praxis Research Site
state: Pennsylvania
city: Media
country: United States
facility: Praxis Research Site
state: Pennsylvania
city: Memphis
country: United States
facility: Praxis Research Site
state: Tennessee
city: Austin
country: United States
facility: Praxis Research Site
state: Texas
city: Charlottesville
country: United States
facility: Praxis Research Site
state: Virginia
city: Everett
country: United States
facility: Praxis Research Site
state: Washington
city: Noble Park
country: Australia
facility: Praxis Research Site
state: Victoria
Study officials:
affiliation: Praxis Precision Mediciines
name: Executive Director Clinical Development
role: STUDY_DIRECTOR
References: