Study design
MDD, psychiatric, depressive disorder
ASPIRE I was conducted from June 2017 to December 2018 in the United States, Europe, Asia, and South Africa. ASPIRE II was conducted from June 2017 to April 2019 in North America, South America, and Europe. Both studies consisted of three phases: (1) a 24- to 48-h screening phase to assess patients’ eligibility for study enrollment, (2) a 4-week double-blind treatment phase (days 1–25), and (3) a 9-week post treatment follow-up phase (days 26–90). During the 4-week double-blind treatment phase, patients were randomly assigned (1:1) to receive either ESK 84 mg or PBO nasal spray twice weekly, in addition to comprehensive SOC treatment (initial psychiatric hospitalization for a recommended ≥ 5 days and newly initiated or optimized oral antidepressant(s), per clinical judgement and practice guidelines) (Fig. Study design of ASPIRE I and ASPIRE II. Two patients in each treatment group were excluded from these analyses because they did not receive a dose of intranasal study drug after randomization. Changes in MADRS total score and CGI-SS-r were assessed at 4 and 24 h post first dose, twice per week pre-dose during the double-blind phase, and at varied time intervals during the follow-up phase (days 28–39: twice weekly; days 46–53: weekly; days 67–90: biweekly). AD, antidepressant; ESK, esketamine; MDD, major depressive disorder; PBO, placebo; SOC, standard of care