Depression, Major Depressive Disorder
Conditions
Keywords
Depressive Disorder, Depressive Disorder, Major, Bupropion, Dextromethorphan, MDD, Dopamine Reuptake Inhibitor, AXS-05, NMDA Receptor Antagonist, Central Nervous System, CNS, Sigma-1 Receptor Agonist, Nicotinic Acetylcholine Receptor Antagonist, Norepinephrine Reuptake Inhibitor, Glutamate Modulator, Axsome Therapeutics, GEMINI, Serotonin Reuptake Inhibitor
Brief summary
A Phase 3, randomized, double-blind, placebo-controlled, multicenter trial of AXS-05 in patients with major depressive disorder (MDD).
Detailed description
This study will evaluate AXS-05 in a randomized, double-blind, placebo-controlled study in patients with MDD. Eligible patients will be randomized in a 1:1 ratio to treatment with AXS-05 or placebo for 6 weeks.
Interventions
DRUGAXS-05
Oral AXS-05 tablets, taken daily for 6 weeks.
DRUGPlacebo
Placebo to match oral AXS-05 tablets, taken daily for 6 weeks.
Sponsors
Axsome Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Age 18 - 65 * Currently meets DSM-5 criteria for MDD * Body Mass Index between 18 and 40 kg/m\^2, inclusive Key
Exclusion criteria
* Suicide risk * History of treatment resistance in current depressive episode * History of electroconvulsive therapy, vagus nerve stimulation, transcranial magnetic stimulation or any experimental central nervous system treatment during the current episode or in the past 6 months * Pregnant, breastfeeding, or planning to become pregnant or breastfeed during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in MADRS Total Score From Baseline to Week 6 | 6 weeks | The primary objective of the study was to evaluate the efficacy of AXS-05 as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) for change in severity of depressive symptoms from baseline to Week 6. The MADRS is a 10-item scale and items are scored between 0-6 points. For each item, a score of 0 indicates the absence of symptoms, and a score of 6 indicates symptoms of maximum severity. A maximum total score is 60 points. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AXS-05 AXS-05 (bupropion and dextromethorphan) oral tablets
AXS-05: Oral AXS-05 tablets, taken daily for 6 weeks. | 163 |
| Placebo Placebo oral tablets to match AXS-05
Placebo: Placebo to match oral AXS-05 tablets, taken daily for 6 weeks. | 164 |
| Total | 327 |
Baseline characteristics
| Characteristic | Placebo | Total | AXS-05 |
|---|---|---|---|
| Age, Continuous | 41.1 years STANDARD_DEVIATION 13.78 | 41.6 years STANDARD_DEVIATION 13.25 | 42.1 years STANDARD_DEVIATION 12.71 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 17 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 55 Participants | 116 Participants | 61 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) White | 92 Participants | 180 Participants | 88 Participants |
| Sex: Female, Male Female | 117 Participants | 215 Participants | 98 Participants |
| Sex: Female, Male Male | 47 Participants | 112 Participants | 65 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 162 | 0 / 164 |
| other Total, other adverse events | 100 / 162 | 74 / 164 |
| serious Total, serious adverse events | 1 / 162 | 0 / 164 |
Outcome results
Primary
Change in MADRS Total Score From Baseline to Week 6
The primary objective of the study was to evaluate the efficacy of AXS-05 as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) for change in severity of depressive symptoms from baseline to Week 6. The MADRS is a 10-item scale and items are scored between 0-6 points. For each item, a score of 0 indicates the absence of symptoms, and a score of 6 indicates symptoms of maximum severity. A maximum total score is 60 points.
Time frame: 6 weeks
Population: modified Intent-to-Treat (mITT) Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AXS-05 | Change in MADRS Total Score From Baseline to Week 6 | 15.91 score on a scale | Standard Error 0.921 |
| Placebo | Change in MADRS Total Score From Baseline to Week 6 | 12.04 score on a scale | Standard Error 0.862 |
p-value: 0.002Mixed Models Analysis