Time Dynamics of Adverse Events of Interest Occurring with Esketamine Nasal Spray and Quetiapine Extended Release: Results from the ESCAPE‑TRD Phase IIIb Trial

We thank the patients who participated. This study was funded by Janssen, medical writing by Costello Medical, UK. INTRODUCTION In ESCAPE-TRD, esketamine nasal spray (ESK-NS) significantly increased the probability of remission at Week (Wk) 8, and being relapse‑free through Wk32 after remission at Wk8, versus quetiapine extended release (QTP-XR), in patients with treatment resistant depression (TRD). Fewer treatment emergent adverse events (TEAEs) led to discontinuation with ESK-NS versus QTP-XR; safety data were consistent with the established profiles of each treatment, with no new safety signals/concerns. Here, we report time dynamics of TEAEs. METHODS ESCAPE‑TRD (NCT04338321) was a randomized phase IIIb trial comparing efficacy and safety of ESK-NS versus QTP-XR, both alongside a selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor, in patients with TRD. Median durations of commonly reported TEAEs were assessed in patients who received ≥1 study treatment dose using Kaplan-Meier analyses; missing/incomplete TEAE start/end dates were imputed. RESULTS 336 and 340 patients were randomized to ESK-NS and QTP-XR, respectively; 334 and 336 were included in the safety population. Among commonly reported TEAEs were dizziness and somnolence. The median duration (days) of dizziness was shorter with ESK-NS (1.0; 95% CI: non-estimable; 1,510 events [156 patients]) versus QTP-XR (14.0; 95% CI: 7.0, 27.0; 29 events [28 patients]). Median duration of somnolence was shorter with ESK-NS (1.0; 95% CI: non-estimable; 570 events [50 patients]) versus QTP-XR (15.0; 95% CI: 12.0, 20.0; 110 events [78 patients]). CONCLUSIONS Although TEAEs were more common with ESK-NS than QTP-XR, they were typically of shorter duration and may have been better tolerated, contributing to lower treatment discontinuation rates with ESK-NS than QTP-XR.