Trial Outcomes & Findings for Open-Label Safety Study of AXS-05 in Subjects With TRD (EVOLVE) (NCT NCT04634669)

NCT ID: NCT04634669

Last Updated: 2026-01-28

Results Overview

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 181 participants
• Primary outcome timeframe: 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 posted on: 2026-01-28

Participant Flow

Participant milestones

Measure	AXS-05 AXS-05 tablet, taken twice daily (up to 15 months)
Overall Study STARTED	181
Overall Study COMPLETED	11
Overall Study NOT COMPLETED	170

Reasons for withdrawal

Measure	AXS-05 AXS-05 tablet, taken twice daily (up to 15 months)
Overall Study Study Terminated by Sponsor	95
Overall Study Withdrawal by Subject	20
Overall Study All Other Reasons	55

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	AXS-05 n=181 Participants AXS-05 tablet, taken twice daily (up to 15 months)
Age, Continuous	46.6 years STANDARD_DEVIATION 13.1 • n=158 Participants
Sex: Female, Male Female	113 Participants n=158 Participants
Sex: Female, Male Male	68 Participants n=158 Participants
Race/Ethnicity, Customized White	144 Participants n=158 Participants
Race/Ethnicity, Customized Black or African American	29 Participants n=158 Participants
Race/Ethnicity, Customized Asian	3 Participants n=158 Participants
Race/Ethnicity, Customized Other	3 Participants n=158 Participants
Race/Ethnicity, Customized Multiple	2 Participants n=158 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	AXS-05 n=181 Participants AXS-05 tablet, taken twice daily for up to 15 months
Incidence of Treatment-emergent AEs (TEAEs) Following Dosing With AXS-05 Subjects with any TEAEs	112 Participants
Incidence of Treatment-emergent AEs (TEAEs) Following Dosing With AXS-05 Subjects with suspected to be drug-related TEAEs	65 Participants
Incidence of Treatment-emergent AEs (TEAEs) Following Dosing With AXS-05 Subjects with serious TEAEs	7 Participants
Incidence of Treatment-emergent AEs (TEAEs) Following Dosing With AXS-05 Subjects with TEAEs that led to drug withdrawal	16 Participants
Incidence of Treatment-emergent AEs (TEAEs) Following Dosing With AXS-05 Subjects with TEAEs that led to withdrawal from study	14 Participants
Incidence of Treatment-emergent AEs (TEAEs) Following Dosing With AXS-05 Subjects with TEAEs that resulted in death	0 Participants

Adverse Events

AXS-05

Serious events: 7 serious events

Other events: 38 other events

Deaths: 0 deaths

Serious adverse events

Measure	AXS-05 n=181 participants at risk AXS-05 tablet, taken twice daily for up to 15 months
Endocrine disorders Inappropriate antidiuretic hormone secretion	0.55% 1/181 • Number of events 1 • 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.
Hepatobiliary disorders Cholecystitis	0.55% 1/181 • Number of events 1 • 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.
Infections and infestations COVID-19 pneumonia	0.55% 1/181 • Number of events 1 • 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.
Infections and infestations Coronavirus infection	0.55% 1/181 • Number of events 1 • 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.
Infections and infestations Urinary tract infection	0.55% 1/181 • Number of events 1 • 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.
Injury, poisoning and procedural complications Procedural pain	0.55% 1/181 • Number of events 1 • 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.
Metabolism and nutrition disorders Hyponatraemia	0.55% 1/181 • Number of events 1 • 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.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.55% 1/181 • Number of events 1 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.55% 1/181 • Number of events 1 • 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.
Nervous system disorders Metabolic encephalopathy	0.55% 1/181 • Number of events 1 • 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.
Psychiatric disorders Suicidal ideation	0.55% 1/181 • Number of events 1 • 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.
Reproductive system and breast disorders Ovarian cyst	0.55% 1/181 • Number of events 1 • 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 adverse events

Measure	AXS-05 n=181 participants at risk AXS-05 tablet, taken twice daily for up to 15 months
Infections and infestations Covid-19	8.3% 15/181 • Number of events 15 • 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.
Gastrointestinal disorders Nausea	8.3% 15/181 • Number of events 15 • 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.
Nervous system disorders Headache	6.6% 12/181 • Number of events 15 • 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.

Additional Information

Caroline Streicher, Senior Vice President, Clinical Research

Axsome Therapeutics, Inc

Phone: 212-332-5061

Email: cstreicher@axsome.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place