Treatment Resistant DepressionPhase 2NCT04634669

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

A Phase 2 study testing AXS-05 (dextromethorphan-bupropion) in people with Treatment Resistant Depression and Major Depressive Disorder, run by Axsome Therapeutics, Inc. at 20 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

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 Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Treatment Resistant Depression, Major Depressive Disorder
What is being tested?: AXS-05 (dextromethorphan-bupropion)
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 181 participants
Where: 20 sitesUnited States
Study dates: 23 Sep 2020to 4 Mar 2022
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

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

Trial locations and contacts

20 sites in 1 country.

City, postcode or hospital

20 sites in 1 country

United States20 sites

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

Other trials in United States

About this study

Official title: 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

Read the 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.

Conditions: Treatment Resistant Depression, Major Depressive Disorder
Being tested: AXS-05 (dextromethorphan-bupropion)
Keywords: AXS-05, Treatment Resistant Depression, TRD, NMDA receptor, Refractory depression, Resistant depression, Depression, Major depression, Dextromethorphan, Bupropion, MDD
Medical subject headings: Depressive Disorder, Treatment-Resistant, Depressive Disorder, Major, Depression

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AXS-05 (dextromethorphan-bupropion)Drug
- Titrated to AXS-05 (45 mg dextromethorphan HBr / 105 mg bupropion HCl) twice daily (up to 15 months)

Study groups in NCT04634669
Study group	Role	What they receive
AXS-05 (dextromethorphan-bupropion)	Experimental	Not described Receives: Drug: AXS-05 (dextromethorphan-bupropion)

What is being measured

The primary outcome is the main question the study is designed to answer.

Incidence of Treatment-emergent AEs (TEAEs) Following Dosing With AXS-05
Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

23 Sep 20204 Mar 2022

First posted18 Nov 2020
Study start23 Sep 2020
Primary completion18 Feb 2022
Study completion4 Mar 2022

Why it stopped: This study was terminated once overall program objectives were met.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Treatment Resistant DepressionStudies of the same condition, open and under way.
More trials run by Axsome Therapeutics, Inc.The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 181 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04634669
Sponsor's protocol ID: AXS-05-TRD-202
Status last verified: Jan 2026
First submitted: 12 Nov 2020
Last updated: 28 Jan 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 4
Biomarker-Guided Antidepressant Selection
Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)
RecruitingPhase 2
ACP-211 Monotherapy for Major Depressive Disorder With Inadequate Antidepressant Response
Major Depressive Disorder (MDD), Depressive Disorder, Treatment-Resistant
Active, not recruiting
CET- REM (Correlating ECT Response to EEG Markers)
ECT, Treatment Resistant Depression
Active, not recruiting
rTMS to Target Neural Connectivity and Rumination in Treatment-Resistant Depression
Depression, Treatment Resistant
Recruiting
A Prospective, Multi-center, Randomized Controlled Blinded Trial Demonstrating the Safety and Effectiveness of VNS Therapy® System as Adjunctive Therapy Versus a No Stimulation Control in Subjects With Treatment-Resistant Depression
Treatment Resistant Depression

All Treatment Resistant Depression trials

Study at a glance

From the registry record, last updated by the sponsor on 28 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-Label Study to Assess the Long-term Safety and Efficacy of AXS-05 in Subjects With Treatment Resistant Depression
ClinicalTrials.gov ID: NCT04634669
Acronym / sponsor ID: AXS-05-TRD-202
Conditions: Treatment Resistant Depression, Major Depressive Disorder
Keywords: AXS-05, Treatment Resistant Depression, TRD, NMDA receptor, Refractory depression, Resistant depression, Depression, Major depression
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: This study was terminated once overall program objectives were met.
Enrolment: 181 participants (actual)
Lead sponsor: Axsome Therapeutics, Inc.Industry (pharma, biotech, devices)
Study start: 23 Sep 2020 (actual)
Primary completion: 18 Feb 2022 (actual)
Study completion: 4 Mar 2022 (actual)
First posted: 18 Nov 2020 (actual)
Results: Posted 28 Jan 2026

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
AXS-05 (dextromethorphan-bupropion)	Experimental	Drug: AXS-05 (dextromethorphan-bupropion)

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AXS-05 (dextromethorphan-bupropion)- Titrated to AXS-05 (45 mg dextromethorphan HBr / 105 mg bupropion HCl) twice daily (up to 15 months)	Drug	AXS-05 (dextromethorphan-bupropion)

Primary outcome

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.

Results and safety

Results posted to the registry on 28 Jan 2026, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
AXS-05	181	11

Primary outcome: 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.. Count of participants. Unit: Participants

Measure	AXS-05 n = 181
Subjects with any TEAEs	112
Subjects with suspected to be drug-related TEAEs	65
Subjects with serious TEAEs	7
Subjects with TEAEs that led to drug withdrawal	16
Subjects with TEAEs that led to withdrawal from study	14
Subjects with TEAEs that resulted in death	0

Adverse events

Group	Serious adverse events	Other adverse events	Deaths
AXS-05	7 of 181 (3.9%)	38 of 181 (21%)	0 of 181

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Axsome Therapeutics WebsiteLink provided by the sponsor.
Individual participant dataSharing planned: No

Related trials for Treatment Resistant Depression

RecruitingPhase 4
Biomarker-Guided Antidepressant Selection
Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)
RecruitingPhase 2
ACP-211 Monotherapy for Major Depressive Disorder With Inadequate Antidepressant Response
Major Depressive Disorder (MDD), Depressive Disorder, Treatment-Resistant
Active, not recruiting
CET- REM (Correlating ECT Response to EEG Markers)
ECT, Treatment Resistant Depression
Active, not recruiting
rTMS to Target Neural Connectivity and Rumination in Treatment-Resistant Depression
Depression, Treatment Resistant
Recruiting
A Prospective, Multi-center, Randomized Controlled Blinded Trial Demonstrating the Safety and Effectiveness of VNS Therapy® System as Adjunctive Therapy Versus a No Stimulation Control in Subjects With Treatment-Resistant Depression
Treatment Resistant Depression

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

20 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing AXS-05 (dextromethorphan-bupropion) in people with Treatment Resistant Depression and Major Depressive Disorder, run by Axsome Therapeutics, Inc. at 20 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 28 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Jan 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04634669.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2026.