COMET Phase 3 Study

COMET was a Phase 3, multicenter, open-label US study. Patients with MDD were treated with AUVELITY twice daily in a 12-month study.
The study enrolled both patients completing a prior AUVELITY study and newly enrolled patients. The trial was concluded once at least 300 patients had been treated for 6 months and at least 100 patients had been treated for 12 months, as prespecified. At the time of study conclusion, 597 patients had reached at least 6 months, and 110 patients had reached at least 12 months of treatment.^1-3

Efficacy endpoint results were based on the newly enrolled patients (n=609) and the safety results from the full population (N=876).^4,6

All newly enrolled patients were assessed for efficacy through Week 6. Only patients whose MADRS scores improved by ≥25% were eligible to continue in the study. 6% of subjects met discontinuation criteria at Week 6.^1,7

Select secondary endpoints include: Clinical remission (MADRS total score ≤10), clinical response (≥50% improvement in MADRS total score from baseline), CGI-I, and SDS.¹

Clinical response and clinical remission were assessed on the MADRS scale. The MADRS is a clinician-rated scale used to assess depressive symptom severity. Patients are rated on 10 items to assess feelings of sadness, inner tension, reduced sleep or appetite, difficulty concentrating, lassitude, lack of interest, pessimism, and suicidality. Scores range from 0 to 60, with higher scores indicating more severe depression.^1,5

Footnotes and Definitions

BID=twice a day; CGI-I=Clinical Global Impression-Improvement; MADRS=Montgomery-Åsberg Depression Rating Scale; MDD=major depressive disorder; SDS=Sheehan Disability Scale.

References

1. Data on File. Axsome Therapeutics, Inc. DOF-AUV-00443.
2. Jones A, O'Gorman C, Tabuteau H. Sustained efficacy and long-term safety of AXS-05, an oral NMDA receptor antagonist, in major depressive disorder: COMET study results. Poster presented at: American Psychiatric Association Annual Meeting; May 2021; Online.
3. Guidance for Industry: Premarketing Risk Assessment. US Department of Health and Human Services Food and Drug Administration. March 2005. Accessed December 8, 2024. https://www.fda.gov/media/71650/download
4. Data on File. Axsome Therapeutics, Inc. DOF-AUV-00442.
5. AUVELITY [Prescribing Information]. Axsome Therapeutics, Inc.: New York, NY.
6. Data on File. Axsome Therapeutics, Inc. DOF-AUV-00441.
7. Iosifescu DV, Jones A, O'Gorman C, et al. Efficacy and safety of AXS-05 (dextromethorphan-buproprion) in patients with major depressive disorder: a phase 3 randomized clinical trial (GEMINI). J Clin Psychiatry. 2022;83(4):21m14345.