A Study to Evaluate the Efficacy, Safety, and Tolerability of Flexible Doses of Intranasal Esketamine Plus an Oral Antidepressant in Adult Participants With Treatment-resistant Depression
Condition: Treatment-resistant Depression
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this study is to compare the efficacy and safety of switching
      treatment-resistant depression (TRD) subjects from a prior antidepressant treatment (to which
      they have not responded) to either intranasal esketamine plus a new oral antidepressant or
      switching to a new oral antidepressant plus intranasal placebo.
    

Detailed description: 
      This is a randomized, double-blind (neither the researchers nor the subjects know what
      treatment the subject is receiving), active-controlled, multicenter study (more than 1 study
      site) in subjects with TRD to assess the efficacy, safety, and tolerability of flexible doses
      of intranasal esketamine plus a newly initiated oral antidepressant compared with a newly
      initiated oral antidepressant (active comparator) plus intranasal placebo. The study will
      consist of 3 phases: Screening/Prospective Observational Phase (4-7 weeks), Double-blind
      Induction Phase (4-weeks), Follow-up Phase (24-weeks). Subjects who rollover into a long-term
      maintenance study will not participate in the Follow-up Phase. The antidepressant treatment,
      as well as any other ongoing medications being taken for depression at screening (including
      adjunctive/ augmentation therapies), will continue unchanged, at the same dosage, from the
      start of Week 1 through the end of Week 4 of the screening/prospective observational phase.
      Subjects' safety will be monitored throughout the study.
    

Intervention name(s): Esketamine; Placebo; Duloxetine (Oral Antidepressant); Escitalopram (Oral antidepressant); Sertraline (Oral Antidepressant); Venlafaxine Extended Release (XR) (Oral Antidepressant)
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Participants will self-administer either 56 mg or 84 mg of esketamine, intranasally, twice per week as a flexible dose regimen in the Double-Blind Induction Phase.; Participants will self-administer matching placebo, intranasally, twice per week for 4 weeks as a flexible dose regimen in the Double-Blind Induction Phase.; Duloxetine could be selected as the oral antidepressant medication by the investigator based on review of Massachusetts General Hospital - Antidepressant Treatment Response Questionnaire (MGH-ATRQ) and relevant prior antidepressant medication information. The minimum therapeutic dose is 60 milligram per day (mg/day).; Escitalopram could be selected as the oral antidepressant medication by the investigator based on review of MGH-ATRQ and relevant prior antidepressant medication information. Escitalopram will be titrated upto a dose of 20 mg/day, but if not tolerated the dose can be reduced to the minimum therapeutic dose of 10 mg/day.; Sertraline could be selected as the oral antidepressant medication by the investigator based on review of MGH-ATRQ and relevant prior antidepressant medication information. Sertraline will be titrated upto a dose of 150 mg/day, but if not tolerated the dose can be reduced to the minimum therapeutic dose of 50 mg/day.; Venlafaxine Extended Release could be selected as the oral antidepressant medication by the investigator based on review of MGH-ATRQ and relevant prior antidepressant medication information. Venlafaxine Extended Release will be titrated upto a dose of 225 mg/day, but if not tolerated the dose can be reduced to the minimum therapeutic dose of 150 mg/day.
Intervention MeSH terms: Duloxetine Hydrochloride; Venlafaxine Hydrochloride; Sertraline; Antidepressive Agents; Esketamine; Escitalopram
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Treatment-resistant Depression; Esketamine; Placebo; Oral Antidepressant