NCT02493868

A Study of Intranasal Esketamine Plus an Oral Antidepressant for Relapse Prevention in Adult Participants With Treatment-resistant Depression

A Randomized, Double-blind, Multicenter, Active-Controlled Study of Intranasal Esketamine Plus an Oral Antidepressant for Relapse Prevention in Treatment-resistant Depression

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 719 (actual)
• Sponsor: Janssen Research & Development, LLC · Industry
• Sex: All
• Age: 18 Years – 64 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to assess the efficacy of intranasal esketamine plus an oral antidepressant compared with an oral antidepressant (active comparator) plus intranasal placebo in delaying relapse of depressive symptoms in participants with treatment-resistant depression (TRD) who are in stable remission after an induction and optimization course of intranasal esketamine plus an oral antidepressant.

Detailed description

This is a randomized, double-blind (neither the researchers nor the participant know what treatment the participants is receiving), active-controlled, multicenter (more than 1 study site) study in participants with TRD to assess the efficacy of intranasal esketamine plus an oral antidepressant compared with an oral antidepressant (active comparator) plus intranasal placebo in delaying relapse of depressive symptoms. The study will consist of 5 phases: Screening/Prospective Observational Phase (4-7weeks) for direct-entry participants only, Open-label Induction Phase (4-weeks) for direct-entry participants only, Optimization Phase (12-weeks; open-label for direct-entry participants and double-blind for transferred-entry participants), Maintenance Phase (variable duration; double-blind for all participants) and Follow-up Phase (2-weeks). Participants' safety will be monitored throughout the study.

Conditions

• Depressive Disorder, Treatment-Resistant

Interventions

Type	Name	Description
DRUG	Esketamine	Open-label induction phase: Direct entry participants start at a dose of 56 mg on Day 1. On Day 4, the dose may be increased to 84 mg or remain at 56 mg. From Day 8 to 22, dose may be increased to 84 mg, remain the same or be reduced to 56 mg from 84 mg per protocol, at investigator's discretion based on efficacy and/or tolerability. On Day 25, a dose reduction from 84 mg to 56 mg is permitted but no dose increase is permitted. Optimization Phase: Direct-entry and transferred-entry participants will self-administer intranasal esketamine (same dose) for first 4 weeks, then individualized to either once weekly or once every other week based on depressive symptoms. Maintenance Phase: All participants assigned to esketamine will self-administer intranasal esketamine once weekly or once every other week based on depressive symptoms.
DRUG	Placebo	Optimization Phase: Transferred-entry participant will self-administer intranasal placebo at weekly treatment sessions for the first 4 weeks of this phase, then individualized to either once weekly or once every other week based on depressive symptoms. Maintenance Phase: Direct-entry and transferred-entry participants assigned to placebo will self-administer matching intranasal placebo once weekly or once based on depressive symptoms.
DRUG	Duloxetine (Oral Antidepressant)	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).
DRUG	Escitalopram (Oral antidepressant)	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 maximum dose of 20 mg/day, but if not tolerated the dose can be reduced to the minimum therapeutic dose of 10 mg/day.
DRUG	Sertraline (Oral Antidepressant)	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 maximum dose of 200 mg/day, but if not tolerated the dose can be reduced to the minimum therapeutic dose of 50 mg/day.
DRUG	Venlafaxine Extended Release (XR) (Oral Antidepressant)	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 maximum dose of 225 mg/day, but if not tolerated the dose can be reduced to the minimum therapeutic dose of 150 mg/day.

Timeline

• Start date: 2015-10-01
• Primary completion: 2018-02-15
• Completion: 2018-02-16
• First posted: 2015-07-10
• Last updated: 2025-04-29
• Results posted: 2019-05-21

Locations

155 sites across 15 countries: United States, Belgium, Brazil, Canada, Czechia, Estonia, France, Germany, Hungary, Mexico, Poland, Slovakia, Spain, Sweden, Turkey (Türkiye)