This Phase III, double-blind, randomised, placebo-controlled trial (n=258) will evaluate the efficacy and safety of intranasal esketamine 84 mg in addition to comprehensive standard of care for rapidly reducing symptoms of major depressive disorder (MDD) in adolescent participants aged 12 to 17 with acute suicidal ideation or behaviour. The primary outcome is the change in depressive symptoms measured by the Children's Depression Rating Scale - Revised (CDRS-R) total score at 24 hours post-first dose. Participants will be randomly assigned to receive either intranasal esketamine (84 mg, with potential dose adjustments to 56 mg) plus oral placebo or intranasal placebo plus oral midazolam (0.0625 mg/kg) twice weekly for four weeks. The treatment will occur on specific days, with assessments conducted to monitor the efficacy and safety of the interventions. The trial is sponsored by Janssen Research & Development, LLC, with an estimated start date of January 8, 2026, and a completion date of September 15, 2031.
The purpose of this study is to evaluate how well JNJ-54135419 works (efficacy) in addition to comprehensive standard of care (SoC) in rapidly reducing the symptoms of major depressive disorder (MDD, a mental disorder characterized by a persistent feeling of sadness and loss of interest in activities) as compared with psychoactive placebo (does not contain JNJ-54135419) plus SoC in adolescent participants with acute suicidal ideation or behavior.
Participants will receive intranasal esketamine 84 milligrams (mg) along with oral placebo solution twice weekly for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25). On Day 4 a decrease to intranasal esketamine 56 mg (in a blinded fashion per investigator's judgment) is permitted. Thereafter, dose may be flexed between 56 mg and 84 mg during the treatment period.
Participants will receive intranasal esketamine 84 milligrams (mg) along with oral placebo solution twice weekly for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25). On Day 4 a decrease to intranasal esketamine 56 mg (in a blinded fashion per investigator's judgment) is permitted. Thereafter, dose may be flexed between 56 mg and 84 mg during the treatment period.
Participants will receive oral midazolam (0.0625 milligrams per kilograms \[mg/kg\]) and intranasal placebo twice weekly for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25). On Day 4 a sham decrease to esketamine 56 mg dose (in a blinded fashion per investigator's judgment) is permitted. Thereafter, sham dose may be flexed between 56 mg and 84 mg during the treatment period.
Unmatched intervention: Midazolam