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Label indication AUVELITY is a combination of dextromethorphan, an uncompetitive N -methyl D -aspartate (NMDA) receptor antagonist and sigma-1 receptor agonist, and bupropion, an aminoketone and CYP450 2D6 inhibitor, indicated for the treatment of major depressive disorder (MDD) in adults ( 1.1 ) the treatment of agitation associated with dementia due to Alzheimer’s disease ( 1.2 ) Limitations of Use: AUVELITY is not indicated as an… FDA label
Also known as AXS-05 (dextromethorphan-bupropion), Dextromethorphan-Bupropion, Auvelity, DXM-BUP
AXS-05 · 12 trials · 13 indications
The Cohen-Mansfield Agitation Inventory (CMAI) is a 29-item caregiver-rated questionnaire that assesses the frequency of agitation-related and disruptive behaviors in subjects with dementia. The scale contains 29 behaviors or items organized into four subscales: physically aggressive, physically non-aggressive, verbally aggressive, and verbally non-aggressive. The CMAI is administered by interviewing the caregiver and asking him or her to rate the frequency with which the subject manifests each behavior using a seven-point scale: 1=never (better outcome), 7=several times an hour (worse outcome). The CMAI total score is the sum of the scores for all of the items in the CMAI. CMAI total scores range from a minimum of 29 (better outcome) to a maximum of 203 (worse outcome).
Incidence of treatment-emergent adverse events following dosing with AXS-05
Types and rates of adverse events
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.
The MADRS is used to assess depressive symptomatology during the previous week. Subjects are rated on 10 items to assess feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating and lack of interest. Each item is scored on a 7-point scale. A score of 0 indicates the absence of symptoms, and a score of 6 indicates symptoms of maximum severity.
Smoking intensity refers to the number of cigarettes smoked per day.
A biochemical marker of smoking intensity.
Change from baseline (Day 1) to endpoint (Day 14) in task-evoked blood oxygen level-dependent (BOLD) signal within striatal regions of interest during the Effort Expenditure for Rewards Task (EEfRT), as measured by functional magnetic resonance imaging (fMRI).
Assessed by clinician-rated scales.
The primary objective of the study was to assess the effect of AXS-05 versus bupropion as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) for change in severity of depressive symptoms. 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.
The Cohen-Mansfield Agitation Inventory (CMAI) is a 29-item caregiver-rated questionnaire that assesses the frequency of agitation-related and disruptive behaviors in subjects with dementia. The scale contains 29 behaviors or items organized into four subscales: physically aggressive, physically non-aggressive, verbally aggressive, and verbally non-aggressive. The CMAI is administered by interviewing the caregiver and asking him or her to rate the frequency with which the subject manifests each behavior using a seven-point scale: 1=never (better outcome), 7=several times an hour (worse outcome). The CMAI total score is the sum of the scores for all of the items in the CMAI. CMAI total scores range from a minimum of 29 (better outcome) to a maximum of 203 (worse outcome).
| Arm | Type | Description |
|---|---|---|
| AXS-05 | EXPERIMENTAL | Up to 12 weeks |
| Bupropion | EXPERIMENTAL | Up to 12 weeks |
| Placebo | PLACEBO_COMPARATOR | Up to 12 weeks |
| AXS-05 (dextromethorphan-bupropion) | EXPERIMENTAL | * Up to 52 weeks in the open-label segment; * Up to 24 weeks in the randomized double-blind segment (if applicable) |
| Bupropion SR | ACTIVE_COMPARATOR | Participants will receive Bupropion SR (Bupropion Sustained Release) for 4 weeks and will be instructed to take 1 tablet two times per day, at least 8 hours apart and 1 hour prior to a meal, and 2 hours after a meal. |
| Single group, open-label treatment arm | EXPERIMENTAL | All participants who meet eligibility criteria and provide informed consent will be assigned to receive daily oral dextromethorphan-bupropion (DXM/BUP) extended release tablets in an open-label manner for a 14-day treatment period. No randomization or masking will be applied, and all participants and researchers will be aware of the study treatment allocation. |
| Name | Type | Description |
|---|---|---|
| AXS-05 (dextromethorphan-bupropion) | DRUG | AXS-05 tablets, taken twice daily for 12 weeks. |
| Bupropion | DRUG | Bupropion tablets, taken twice daily for 12 weeks. |
| Placebo | DRUG | Placebo tablets, taken twice daily for 12 weeks. |
| AXS-05 | DRUG | AXS-05 tablets, taken twice daily |
| AXS-05 (dextromethorphan and bupropion) oral tablets | DRUG | Oral tablets, taken twice daily for up to 12 months. |
| Bupropion SR | DRUG | Bupropion Sustained Release: Take 1 tablet two times per day, at least 8 hours apart and 1 hour prior to a meal, and 2 hours after a meal. |
| Dextromethorphan-Bupropion | DRUG | The generic name of the study drug is dextromethorphan-bupropion (150 mg), which is an oral, extended-release tablet comprised of 45 mg dextromethorphan HBr and 105 mg bupropion HCl. The brand name of this study drug is Auvelity. Eligible participants that provide written informed consent will be assigned to a single-arm, open-label treatment group, for a treatment period of 14 days. Participants in this treatment group will be asked to take one oral dextromethorphan-bupropion extended-release tablet once daily for Days 1-3 of the treatment period. Participants will then be asked to increase their dose to one oral dextromethorphan-bupropion extended-release tablet twice daily, for Days 4-14 of the treatment period. |
Inclusion Criteria: * Male or female, aged 18 to 65 (inclusive) Exclusion Criteria: * Unable to comply with study procedures. * Medically inappropriate for study participation in the opinion of the investigator.
AXS-05 is an investigational oral small molecule therapy being developed by Axsome Therapeutics for central nervous system conditions. Its development programs cover agitation in patients with dementia of the Alzheimer's type, major depressive disorder, treatment resistant depression, and smoking cessation. It is a Phase 3 candidate and has received FDA Breakthrough Therapy and Priority Review designations.
AXS-05 is being studied for the treatment of agitation in patients with dementia of the Alzheimer's type. Three completed Phase 3 trials have evaluated it in this population, including NCT05557409, NCT04947553, and NCT04797715, which enrolled adults aged 65 and older in the United States, Canada, and Puerto Rico.
AXS-05 targets the NMDA receptor. It is an oral small molecule combination of dextromethorphan and bupropion, and the NMDA receptor is the molecular target described for the asset. Its clinical program spans Alzheimer's disease agitation, major depressive disorder, treatment resistant depression, and smoking cessation.
AXS-05 is developed by Axsome Therapeutics, Inc., which trades on the Nasdaq under the ticker AXSM. Axsome is the sponsor of the Phase 3 clinical program evaluating the candidate across Alzheimer's disease agitation, depression, treatment resistant depression, and smoking cessation.
AXS-05 is in Phase 3 clinical development. It is an investigational therapy and has not been established as approved. Four Phase 3 trials are recorded, all randomized, double blind, and placebo controlled, with a combined enrollment of 1,408 participants. One trial is currently recruiting and the other three are completed.
AXS-05 has been evaluated in four Phase 3 trials. NCT07766655, the SUMMIT study of NMDA and sigma-1 in smoking cessation, is recruiting 705 participants. NCT05557409, NCT04947553, and NCT04797715 studied Alzheimer's disease agitation and are completed, enrolling 408, 456, and 178 participants respectively.