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

NCT06029426 | Completed Phase 3 DMC FDA Drug

• 2 other identifiers: NMRA-335140-301KOASTAL-1
• Study Type: interventional
• Target: 383
• Locations: 1 country
• Sites: 64

Brief Summary

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).

Conditions

Major Depressive Disorder

Keywords

Major Depressive Disorder; NMRA-335140; Placebo-controlled; Double-blind; Navacaprant; NMRA335140; NMRA 335140

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Change from Baseline to Week 6 assessed in the Snaith-Hamilton Pleasure Scale (SHAPS) total score

  Baseline and up to Week 6

Study Arms (2)

NMRA-335140 80 milligrams (mg) once daily (QD)

EXPERIMENTAL

Participants will receive a NMRA-335140 tablet at a dose of 80 mg once daily (QD)

Drug: NMRA-335140

Placebo

PLACEBO COMPARATOR

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

Interventions

NMRA-335140 DRUG

Participants will receive NMRA-335140 at a dose of 80 mg QD, orally

Also known as: BTRX 335140, CYM-53093, Navacaprant

NMRA-335140 80 milligrams (mg) once daily (QD)

Placebo DRUG

Placebo will be administered orally

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%.

You may not qualify if:

• 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: 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.

Sponsors & Collaborators

• Neumora Therapeutics, Inc.: lead

Study Sites (64)

Neumora Investigator Site

Huntsville, Alabama, 35801, United States

Location

Neumora Investigator Site

Phoenix, Arizona, 85012, United States

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Neumora Investigator Site

Bentonville, Arkansas, 72712, United States

Location

Neumora Investigator Site-1

Little Rock, Arkansas, 72211, United States

Location

Neumora Investigator Site

Little Rock, Arkansas, 72211, United States

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Neumora Investigator Site

Rogers, Arkansas, 72758, United States

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Neumora Investigator Site

Bellflower, California, 90706, United States

Location

Neumora Investigator Site

Garden Grove, California, 92845, United States

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Neumora Investigator Site

Glendale, California, 91206, United States

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Neumora Investigator Site

Imperial, California, 92251, United States

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Neumora Investigator Site

Lafayette, California, 94549, United States

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Neumora Investigator Site

Long Beach, California, 90807, United States

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Neumora Investigator Site

Los Angeles, California, 90015, United States

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Neumora Investigator Site

Oceanside, California, 92056, United States

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Neumora Investigator Site

Orange, California, 92868, United States

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Neumora Investigator Site

Riverside, California, 92506, United States

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Neumora Investigator Site

San Jose, California, 95124, United States

Location

Neumora Investigator Site #1

Sherman Oaks, California, 91403, United States

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Neumora Investigator Site

Sherman Oaks, California, 91403, United States

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Neumora Investigator Site

Temecula, California, 92591, United States

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Neumora Investigator Site

Torrance, California, 90504, United States

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Neumora Investigator Site

Colorado Springs, Colorado, 80910, United States

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Neumora Investigator Site

Gainesville, Florida, 32607, United States

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Neumora Investigator Site

Hallandale, Florida, 33009, United States

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Neumora Investigator Site

Jacksonville, Florida, 32256, United States

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Neumora Investigator Site

Lauderhill, Florida, 33319, United States

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Neumora Investigator Site

Maitland, Florida, 32751, United States

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Neumora Investigator Site

Miami, Florida, 33122, United States

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Neumora Investigator Site

Miami, Florida, 33125, United States

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Neumora Investigator Site

Miami, Florida, 33183, United States

Location

Neumora Investigator Site

Miami Lakes, Florida, 33016, United States

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Neumora Investigator Site

Orlando, Florida, 32801, United States

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Neumora Investigator Site

Tampa, Florida, 33607, United States

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Neumora Investigator Site

Marietta, Georgia, 30060, United States

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Neumora Investigator Site

Chicago, Illinois, 60634, United States

Location

Neumora Investigator Site

Evanston, Illinois, 60201, United States

Location

Neumora Investigator Site

Warrenville, Illinois, 60555, United States

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Neumora Investigator Site

Boston, Massachusetts, 02116, United States

Location

Neumora Investigator Site

Methuen, Massachusetts, 01844, United States

Location

Neumora Investigator Site

Watertown, Massachusetts, 02472, United States

Location

Neumora Investigator Site

Bloomfield Hills, Michigan, 48302, United States

Location

Neumora Investigator Site

Flowood, Mississippi, 39232, United States

Location

Neumora Investigator Site

Saint Charles, Missouri, 63304, United States

Location

Neumora Investigator Site

Las Vegas, Nevada, 89102, United States

Location

Neumora Investigator Site

Brooklyn, New York, 11224, United States

Location

Neumora Investigator Site

Cedarhurst, New York, 11516, United States

Location

Neumora Investigator Site

New York, New York, 10036, United States

Location

Neumora Investigator Site

Staten Island, New York, 10314, United States

Location

Neumora Investigator Site

Cleveland, Ohio, 44106, United States

Location

Neumora Investigator Site

Columbus, Ohio, 43210, United States

Location

Neumora Investigator Site

Dayton, Ohio, 45417, United States

Location

Neumora Investigator Site

Garfield Heights, Ohio, 44125, United States

Location

Neumora Investigator Site

Allentown, Pennsylvania, 18104, United States

Location

Neumora Investigator Site

Media, Pennsylvania, 19063, United States

Location

Neumora Investigator Site

Plymouth Meeting, Pennsylvania, 19462, United States

Location

Neumora Investigator Site

Memphis, Tennessee, 38119, United States

Location

Neumora Investigator Site

Austin, Texas, 78737, United States

Location

Neumora Investigator Site

Dallas, Texas, 75235, United States

Location

Neumora Investigator Site

Houston, Texas, 77030, United States

Location

Neumora Investigator Site

Houston, Texas, 77090, United States

Location

Neumora Investigator Site

Wichita Falls, Texas, 76309, United States

Location

Neumora Investigator Site

Charlottesville, Virginia, 22903, United States

Location

Neumora Investigator Site

Bellevue, Washington, 98007, United States

Location

Neumora Investigator Site

Everett, Washington, 98201, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

BTRX-335140

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Sponsor will also be blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2023
• First Posted: September 8, 2023
• Study Start: September 20, 2023
• Primary Completion: December 3, 2024
• Study Completion: January 15, 2025
• Last Updated: November 26, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (64)