Open-Label Safety Study of AXS-05 in Subjects With TRD (EVOLVE)

January 12, 2026 updated by: Axsome Therapeutics, Inc.

An Open-Label Study to Assess the Long-term Safety and Efficacy of AXS-05 in Subjects With Treatment Resistant Depression

This study is a multi-center, open-label trial to evaluate the long-term safety and efficacy of AXS-05 in subjects with major depressive disorder with prior treatment failures

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Eligible subjects must have either completed Study AXS-05-TRD-201 immediately prior to enrollment in this study or meet the DSM-5 criteria for major depressive disorder (MDD) without psychotic features.

Study Type

Interventional

Enrollment (Actual)

181

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72209
        • Clinical Research Site
    • California
      • Redlands, California, United States, 92374
        • Clinical Research Site
      • Sherman Oaks, California, United States, 91403
        • Clinical Research Site
      • Upland, California, United States, 91786
        • Clinical Research Site
    • Florida
      • Miami, Florida, United States, 33122
        • Clinical Research Site
      • Miami Lakes, Florida, United States, 33016
        • Clinical Research Site
      • Orlando, Florida, United States, 32081
        • Clinical Research Site
    • Illinois
      • Chicago, Illinois, United States, 60634
        • Clinical Research Site
    • Massachusetts
      • Boston, Massachusetts, United States, 02131
        • Clinical Research Site
    • New Jersey
      • Berlin, New Jersey, United States, 08009
        • Clinical Research Site
    • New York
      • Rochester, New York, United States, 14618
        • Clinical Research Site
      • Staten Island, New York, United States, 10312
        • Clinical Research Site
    • North Carolina
      • Hickory, North Carolina, United States, 28601
        • Clinical Research Site
      • Raleigh, North Carolina, United States, 27609
        • Clinical Research Site
    • Ohio
      • Cincinnati, Ohio, United States, 45215
        • Clinical Research Site
      • Middleburg Heights, Ohio, United States, 44130
        • Clinical Research Site
    • Pennsylvania
      • Media, Pennsylvania, United States, 19063
        • Clinical Research Site
    • Texas
      • Dallas, Texas, United States, 75243
        • Clinical Research Site
      • Friendswood, Texas, United States, 77546
        • Clinical Research Site
    • Washington
      • Everett, Washington, United States, 98201
        • Clinical Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

  • Completed Study AXS-05-TRD-201 OR currently meets the DSM-5 criteria for MDD without psychotic features and with prior antidepressant treatment failure
  • Agree to use adequate method of contraception for the duration of the study
  • Additional criteria may apply

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: AXS-05 (dextromethorphan-bupropion)
Drug: AXS-05 (dextromethorphan-bupropion)
- Titrated to AXS-05 (45 mg dextromethorphan HBr / 105 mg bupropion HCl) twice daily (up to 15 months)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of Treatment-emergent AEs (TEAEs) Following Dosing With AXS-05
Time Frame: Duration of participation was up to 15 months. TEAEs were defined as any AE with an onset date in the interval between the first study treatment dosing date and 7 days after the last study treatment dosing date.
Duration of participation was up to 15 months. TEAEs were defined as any AE with an onset date in the interval between the first study treatment dosing date and 7 days after the last study treatment dosing date.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Montgomery-Åsberg Depression Rating Scale (MADRS)
Time Frame: Up to 15 months
The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.
Up to 15 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Axsome Therapeutics, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 23, 2020

Primary Completion (Actual)

February 18, 2022

Study Completion (Actual)

March 4, 2022

Study Registration Dates

First Submitted

November 12, 2020

First Submitted That Met QC Criteria

November 12, 2020

First Posted (Actual)

November 18, 2020

Study Record Updates

Last Update Posted (Actual)

January 28, 2026

Last Update Submitted That Met QC Criteria

January 12, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AXS-05-TRD-202

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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