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

Sponsor

Praxis Precision Medicines (Industry)

Overall Status

Completed

CT.gov ID

NCT04969510

Collaborator

(none)

110

Enrollment

Locations

Arms

13.3

Actual Duration (Months)

4.6

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: 10 mg PRAX-114 Drug: 20 mg PRAX-114 Drug: 40 mg PRAX-114 Drug: 60 mg PRAX-114 Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

110 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jun 24, 2021

Actual Primary Completion Date :

Jul 15, 2022

Actual Study Completion Date :

Aug 2, 2022

Arms and Interventions

Arm	Intervention/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
Placebo Comparator: Placebo Placebo once daily	Drug: Placebo Once daily oral treatment

Outcome Measures

Primary Outcome Measures

Change from baseline in HAM-D17 total score at Day 15 [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 Outcome Measures

Change from baseline in HAM-D17 total score at Day 29 [29 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.
Change from baseline in HAM-D17 total score at all other time points [4 days, 8 days, 22 days, 36 days, and 43 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.
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]
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).
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]
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).
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]
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.
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]
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.
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]
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.
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]
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).
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]
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.

Other Outcome Measures

Incidence and severity of Adverse Events (AE) [43 days]
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.
Incidence of AEs by preferred term [43 days]
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).
Incidence of Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicidal ideation or behavior [43 days]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Praxis Research Site	Lafayette	California	United States	94549
2	Praxis Research Site	Lemon Grove	California	United States	91945
3	Praxis Research Site	Oceanside	California	United States	92056
4	Praxis Research Site	Redlands	California	United States	92374
5	Praxis Research Site	Jacksonville	Florida	United States	32256
6	Praxis Research Site	Orange City	Florida	United States	32763
7	Praxis Research Site	Orlando	Florida	United States	32801
8	Praxis Research Site	Atlanta	Georgia	United States	30331
9	Praxis Research Site	Decatur	Georgia	United States	30030
10	Praxis Research Site	Gaithersburg	Maryland	United States	20877
11	Praxis Research Site	Boston	Massachusetts	United States	02131
12	Praxis Research Site	Worcester	Massachusetts	United States	01655
13	Praxis Research Site	O'Fallon	Missouri	United States	63368
14	Praxis Research Site	Las Vegas	Nevada	United States	89102
15	Praxis Research Site	Cedarhurst	New York	United States	11516
16	Praxis Research Site	Rochester	New York	United States	14618
17	Praxis Research Site	Dayton	Ohio	United States	45417
18	Praxis Research Site	Allentown	Pennsylvania	United States	18104
19	Praxis Research Site	Media	Pennsylvania	United States	19063
20	Praxis Research Site	Memphis	Tennessee	United States	38119
21	Praxis Research Site	Austin	Texas	United States	78737
22	Praxis Research Site	Charlottesville	Virginia	United States	22903
23	Praxis Research Site	Everett	Washington	United States	98201
24	Praxis Research Site	Noble Park	Victoria	Australia	3174