Introduction: ASPIRE-1 is one of two global phase-3 studies in the registration program to evaluate efficacy and safety of esketamine nasal spray (ESK) vs placebo, with comprehensive standard-of-care (SoC), in patients with major depressive disorder (MDD) at imminent risk for suicide.
Methods: In this double-blind (DB), placebo-controlled study (NCT03039192), patients (aged 18-64 years) with moderate to severe MDD (DSM-5 criteria) who had active suicidal ideation with intent, and required psychiatric hospitalization, were enrolled. Patients were randomized (1:1) to ESK 84-mg or placebo twice-weekly along with comprehensive SoC antidepressants for 4 weeks. Change from baseline to 24-hours post first dose in Montgomery-Ǻsberg Depression Rating Scale (MADRS) total score (primary endpoint) and Clinical Global Impression–Severity of Suicidality–Revised (CGI-SS-R) (key secondary endpoint) were evaluated. Safety assessments were performed.
Results: 225 of 226 randomized patients (mean age: 39.3 years) received placebo+SoC (n=112) or ESK+SoC (n=113); 195/226 (86%) completed DB-phase. At baseline, mean MADRS score was 41.1, and 89% were moderately to extremely suicidal (CGI-SS-R). Patients receiving ESK+SoC showed significant improvement in MADRS total score vs placebo+SoC (LS-mean [SE] difference: -3.8 [1.39]; p=0.006) at 24-hours after first dose. Although improvement in CGI-SS-R was observed in both treatment groups, the between group difference was not significant. Most common treatment-emergent adverse events observed in ESK+SoC were dizziness (35%), dissociation (29%), and nausea (20%).
Conclusion: ESK+SoC treatment was efficacious in rapidly reducing depressive symptoms in MDD patients at imminent risk for suicide. Safety findings were consistent with the established safety profile of ESK.
This poster was presented at the 32nd annual Psych Congress, held Oct. 3-6, 2019, in San Diego, California.