A Study to Evaluate the Efficacy, Safety, and Tolerability of Fixed 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) participants 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 participants know what
      treatment the participant is receiving), active-controlled, multicenter study (more than 1
      study site) in participants with TRD to assess the efficacy, safety, and tolerability of
      fixed 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). Participants who rollover into a
      long-term maintenance study will not participate in the Follow-up Phase. At the start of the
      screening/prospective observational phase, the participant must have had documented
      non-response to at least 1 antidepressant treatment (based on Massachusetts General Hospital
      - Antidepressant Treatment Response Questionnair [MGH-ATRQ]) in the current episode of
      depression, and participant is taking a different oral antidepressant treatment on the
      MGH-ATRQ for at least the previous 2 weeks at or above the minimum therapeutic dose. This
      antidepressant treatment, as well as any other ongoing medications being taken for depression
      at screening (including adjunctive/ augmentation therapies), will continue from the start of
      Week 1 through the end of Week 4 of the screening/prospective observational phase.
      Participants will be randomly assigned to receive Intranasal esketamine (56 milligrams [mg]),
      Intranasal esketamine (84 mg), or Intranasal placebo. In addition, each participant will be
      assigned to receive 1 of 4 oral antidepressant medications from 2 different classes of
      antidepressant treatments, a Selective Serotonin Reuptake Inhibitor (SSRI) (escitalopram or
      sertraline) or a Serotonin and Norepinephrine Reuptake Inhibitor (SNRI) (duloxetine or
      venlafaxine extended release [XR]), initiated on Day 1 and continued through the double-blind
      induction phase. Participants will be primarily evaluated for improvement in depressive
      symptoms as assessed by change in Montgomery-Asberg Depression Rating Scale (MADRS) total
      score at Week 4. Participants' 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 84 mg or 56 mg of esketamine, intranasally, twice per week for 4 weeks as a fixed dose regimen in Double-Blind Induction Phase.; Participants will self-administer matching placebo, intranasally, twice per week for 4 weeks as a fixed dose regimen in 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 up to 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 up to a dose of 200 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 up to 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