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

Major Depressive Disorder Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04969510
• Other study ID #: PRAX-114-214
• Status: Completed
• Phase: Phase 2
• Start date: June 24, 2021
• Est. completion date: August 2, 2022

Study information

• Verified date: August 2022
• Source: Praxis Precision Medicines
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 110
• Est. completion date: August 2, 2022
• Est. primary completion date: July 15, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Disease
• Major Depressive Disorder

Intervention

Drug:
• 10 mg PRAX-114
Once daily oral treatment
• 20 mg PRAX-114
Once daily oral treatment
• 40 mg PRAX-114
Once daily oral treatment
• 60 mg PRAX-114
Once daily oral treatment
• Placebo
Once daily oral treatment

Locations

Country	Name	City	State
Australia	Praxis Research Site	Noble Park	Victoria
United States	Praxis Research Site	Allentown	Pennsylvania
United States	Praxis Research Site	Atlanta	Georgia
United States	Praxis Research Site	Austin	Texas
United States	Praxis Research Site	Boston	Massachusetts
United States	Praxis Research Site	Cedarhurst	New York
United States	Praxis Research Site	Charlottesville	Virginia
United States	Praxis Research Site	Dayton	Ohio
United States	Praxis Research Site	Decatur	Georgia
United States	Praxis Research Site	Everett	Washington
United States	Praxis Research Site	Gaithersburg	Maryland
United States	Praxis Research Site	Jacksonville	Florida
United States	Praxis Research Site	Lafayette	California
United States	Praxis Research Site	Las Vegas	Nevada
United States	Praxis Research Site	Lemon Grove	California
United States	Praxis Research Site	Media	Pennsylvania
United States	Praxis Research Site	Memphis	Tennessee
United States	Praxis Research Site	O'Fallon	Missouri
United States	Praxis Research Site	Oceanside	California
United States	Praxis Research Site	Orange City	Florida
United States	Praxis Research Site	Orlando	Florida
United States	Praxis Research Site	Redlands	California
United States	Praxis Research Site	Rochester	New York
United States	Praxis Research Site	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Praxis Precision Medicines

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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