in patients meeting proxy criteria for MDD with anxiety symptoms1
This post hoc analysis used proxy criteria from the GEMINI trial to align with the DSM-5 criteria for the anxious distress specifier for MDD. See “Post Hoc: Additional Information” for more details.
AUVELITY is not approved for the management of anxiety disorders.
Limitations
This subgroup analysis was post hoc and was not controlled for Type 1 error. No conclusions of statistical significance can be drawn.
in patients meeting proxy criteria for MDD with anxiety symptoms1
Limitations
This subgroup analysis was post hoc and was not controlled for Type 1 error. No conclusions of statistical significance can be drawn.
Post Hoc Analysis: Additional Information1,2
The GEMINI Phase 3 study evaluated AUVELITY vs placebo in 327 patients (n=163 AUVELITY and n=164 placebo) with MDD. Primary endpoint: LS mean change from baseline in MADRS total score at Week 6. Patients with anxiety were not excluded, provided that anxiety had not been the primary focus of clinical attention during the 6 months prior to screening.
The post hoc subgroup analysis measured change in MADRS total score from baseline over 6 weeks in 317 MDD patients–with and without anxiety symptoms at screening–from the GEMINI study (patients with anxiety symptoms: n=115 AUVELITY and n=102 placebo; patients without anxiety symptoms: n=41 AUVELITY and n=59 placebo).
The DSM-5 "with anxious distress" specifier is applied when a patient with a depressive episode presents with at least 2 of the defined anxiety symptoms. In GEMINI, a proxy measure was constructed using available rating scale items to approximate 3 of the 5 DSM-5 criterion. Therefore, classification required meeting at least 2 of 3 criteria.
*A HAM-D item 10 (Psychic anxiety) score of ≥3 is considered a proxy measure for “Fear that something awful may happen” but was not assessed in the GEMINI trial.1,2
†No validated proxy measure was identified for “Feeling that the individual might lose control of himself of herself.”2
DSM-5=Diagnostic and Statistical Manual of Mental Disorders, 5th Edition; HAM-D=Hamilton Depression Rating Scale; LS=least squares; MADRS=Montgomery-Åsberg Depression Rating Scale; MDD=major depressive disorder; QIDS=Quick Inventory of Depressive Symptomatology.
LS mean change from baseline in MADRS total score at Week 6.
Efficacy assessments were performed at Weeks 1, 2, 3, 4, and 6 on the mITT population. The mITT population was defined as all randomized patients who took at least 1 dose of study drug and had at least 1 post-baseline assessment. Examination of demographic subgroups by age, sex, and race did not suggest differences on the primary endpoint.1
BID=twice a day; LS=least squares; MADRS=Montgomery-Åsberg Depression Rating Scale; mITT=modified intention-to-treat.
Not actual patients.
Demographic and baseline disease characteristics were generally similar across both treatment groups
AA=African American; BID=twice a day; BMI=body mass index; MADRS=Montgomery-Åsberg Depression Rating Scale; MDD=major depressive disorder; PHQ-9=Patient Health Questionnaire-9.
*Naïve=patients who have not been on another antidepressant treatment during their current depressive episode.3
*mITT population.1
BID=twice a day; DSM-5=Diagnostic and Statistical Manual of Mental Disorders, 5th Edition; LS=least squares; MADRS=Montgomery-Åsberg Depression Rating Scale.
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
BID=twice a day; CGI-I=Clinical Global Impression-Improvement; MADRS=Montgomery-Åsberg Depression Rating Scale; MDD=major depressive disorder; SDS=Sheehan Disability Scale.