ASPIRE (A double-blind, randomized, placebo-controlled study to evaluate the efficacy and safety of intranasal esketamine in addition to comprehensive standard of care for the rapid reduction of the symptoms of major depressive disorder, including suicidal ideation, in subjects assessed to be at imminent risk for suicide)
Jeffrey I. Bennett, MD (Faculty, Adult Division)
Vinod Alluri, MD (Faculty, Adult Division)
Michelle Gates, PhD (Faculty, Division of Clinical Psychology)
Santosh Shrestha, MD (Faculty, Adult Division)
Arindam Chakrabarty, MD (Resident)
Background: Major depressive disorder (MDD) is the most prevalent mental health condition and the psychiatric diagnosis most commonly associated with suicide. Epidemiology studies suggest that nearly 60% of those who die by suicide suffer from affective disorders, and at least one-half of people who complete suicide are depressed at the time of their deaths. Although MDD with imminent risk for suicide is a potentially lethal condition that requires immediate intervention, there is no approved treatment.
The mechanism of action of esketamine is distinct from conventional monoaminergic antidepressant treatments, and esketamine profoundly affects fast excitatory glutamate transmission, increases brain-derived neurotrophic factor (BDNF) release, and stimulates synaptogenesis. In addition, a higher NMDA receptor binding affinity of esketamine compared to ketamine allows a lower volume of medication to be administered via the non-invasive and rapidly-absorbed intranasal route.
Objective: The current study is being conducted to evaluate the efficacy and safety of intranasal esketamine in addition to comprehensive standard of care in subjects with MDD who are at imminent risk for suicide as a pivotal Phase 3 study in support of regulatory agency requirements for registration of intranasal esketamine.
Design: This is a randomized, double-blind, placebo-controlled, multicenter study. A target of 224 male and female subjects, 18 to 64 years of age, with MDD presenting to an emergency room (ER) or other permitted setting and assessed to be at imminent risk for suicide will be enrolled in this study.