Study to Evaluate the Effects of Oral NMRA 335140 Versus Placebo in Participants With Major Depressive Disorder

Study Overview
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Brief Summary
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This is a randomized, double blind, placebo controlled, multi-center study to evaluate the effects of NMRA 335140 (formerly BTRX 335140) on symptoms of depression in participants with Major Depressive Disorder (MDD). The study design consists of a Screening Period (up to 28 days), and a 6-week Treatment Period (during which participants will receive either NMRA 335140 or placebo). At the completion of the 6-week Treatment Period, participants who complete the study, provide informed consent, and meet the eligibility criteria may enter an extension study (NMRA 335140 501).

Official Title
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A Phase 3, Randomized, Double Blind, Placebo Controlled Study to Evaluate the Effects of Oral NMRA 335140 Versus Placebo in Participants With Major Depressive Disorder

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: NMRA 335140
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key inclusion criteria: Have a primary Diagnostic and Statistical Manual of Mental Disorders Fifth Edition Text Revised (DSM-5-TR) diagnosis of MDD without psychotic features confirmed by Structured Clinical Interview for DSM 5 Disorders, Clinical Trials Version (SCID 5 CT) at screening (this may be a first or recurrent episode). Participant's current major depressive episode must be confirmed by independent assessment. The symptoms of the current MDD episode have been present for more than 4 weeks prior to the Screening Visit, but no longer than 12 months prior to the Screening Visit. Have a MADRS total score of 25 or higher at Screening and Baseline. A change in MADRS total score between Screening and Baseline of ≤20%. Key exclusion criteria: Have failed 2 or more courses of antidepressant treatment at sufficient doses for at least 6 to 8 weeks for the current MDD episode. Currently or in the past year have been diagnosed with a personality disorder per the DSM-5-TR or in the past 3 years have been diagnosed with any of the following DSM-5-TR disorders: personality disorder, anorexia nervosa, bulimia nervosa, or binge eating disorder. Participants with comorbid generalized anxiety disorder, social anxiety disorder, simple phobias, or panic disorder for whom MDD is considered the primary diagnosis are not excluded. Have a lifetime diagnosis of bipolar 1 or 2, schizophrenia, schizoaffective, schizophreniform, obsessive compulsive disorder, or posttraumatic stress disorder (PTSD). Have moderate to severe substance or alcohol use disorder, per DSM-5-TR criteria, within the 12 months prior to screening (excluding nicotine). Are actively suicidal (e.g., any suicide attempts within the past 12 months) or are at serious suicidal risk as indicated by any current suicidal intent, including a plan, as assessed by the Columbia Suicide Severity Rating Scale (C SSRS) (score of YES on suicidal ideation Item 4 or 5 within 3 months prior to Visit 1 [screening]) and/or based on clinical evaluation by the Investigator; or are homicidal, in the opinion of the Investigator. Participants who are currently hospitalized for MDD symptoms or suicidality are not allowed into the study. If there is a recent history (within 3 months of screening) of hospitalization due to MDD symptoms, the participant should be discussed with the Medical monitor for eligibility.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NMRA-335140 80 milligrams (mg) once daily (QD)<br>Participants will receive a NMRA- 335140 tablet at a dose of 80 mg once daily (QD) | Drug: NMRA 335140<br>* Participants will receive NMRA-335140 at a dose of 80 mg QD, orally<br>* Other names: Navacaprant;|
| Placebo Comparator: Placebo<br>Placebo participants will receive matching placebo tablet orally, once daily. Participants who complete the study may be eligible to participate in a separate 52-week open-label long term study. | Drug: Placebo<br>* Placebo will be administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline to Week 6 in the Montgomery Asberg Depression Rating Scale (MADRS) total score | The MADRS is a 10-item, clinician-rated scale that evaluates the participant's depressive symptomatology during the past week. Participants are rated on items assessing feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty in concentration, and lack of interest. Each item will be scored on a 7-point scale with a score of 0 reflecting no symptoms and a score of 6 reflecting symptoms of maximum severity. Thus, scores in the MADRS range from 0 to 60, with increasing scores indicating increasing severity. | Baseline and up to Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline to Week 6 assessed in the Snaith-Hamilton Pleasure Scale (SHAPS) total score | The SHAPS is a 14 item participant-reported instrument which measures anhedonia. It has been shown to be valid and reliable in normal and clinical samples, with adequate construct validity, satisfactory test-retest reliability and high internal consistency. The scale will be completed by the participant and reviewed by site personnel qualified to oversee completeness. Each of the 14 items has a set of 4 responses, 2 of which endorse agreement (Definitely Agree, Agree) and 2 of which endorse disagreement (Disagree, Strongly Disagree). A total score can be derived by summing the response items, where those answered with strongly agree will be coded as a 1, while a strongly disagree response will be coded as 4. Therefore, scores on the SHAPS can range from 14 to 56, with higher scores corresponding to higher levels of anhedonia. | Baseline and up to Week 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Major Depressive Disorder, NMRA-335140, Placebo-controlled, Double-blind, Navacaprant