NCT03852160

A Study of Esketamine Nasal Spray Plus a New Standard-of-care Oral Antidepressant or Placebo Nasal Spray Plus a New Standard-of-care Oral Antidepressant in Adult and Elderly Participants With Treatment-resistant Depression

A Randomized, Double-Blind, Active-Controlled, International, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of Flexibly-dosed Esketamine Nasal Spray Plus a New Standard-of-care Oral Antidepressant or Placebo Nasal Spray Plus a New Standard-of-care Oral Antidepressant in Adult and Elderly Participants With Treatment-resistant Depression

• Status: Withdrawn
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Janssen-Cilag International NV · Industry
• Sex: All
• Age: 18 Years – 74 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to evaluate the efficacy of treating participants with treatment-resistant depression (TRD) who have failed at least 2 (and no more than 6) prior antidepressant (AD) treatments in the current moderate to severe depressive episode with flexibly-dosed esketamine nasal spray plus a newly initiated oral standard-of-care AD compared with placebo nasal spray plus a newly-initiated standard-of-care oral AD, in achieving remission and staying relapse-free after remission.

Detailed description

Depression is a major cause of morbidity and mortality, with global estimates of 300 million treated and untreated individuals worldwide. In its severe forms, depression is the most common diagnosis associated with suicide. Esketamine (S-ketamine) is the S-enantiomer of ketamine. Ketamine profoundly affects fast excitatory glutamate transmission, increases brain-derived neurotrophic factor release, and stimulates synaptogenesis, in contrast to conventional antidepressants (ADs) which are modulatory transmitters. The goal of any new antidepressant (AD) treatment would be the rapid and long-lasting relief of depressive symptoms. The study includes screening phase (2 weeks, with possible extension up to 4 weeks), Induction phase (Week 1 to Week 4), Maintenance once-weekly phase (Week 5 to Week 8), Maintenance flexible-frequency phase (Week 9 to Week 32) and Follow-up phase (2 Weeks Duration). Total duration of study will be approximately up to 36 weeks. The safety will be monitored throughout the study.

Conditions

• Depressive Disorder, Treatment-Resistant

Interventions

Type	Name	Description
DRUG	Esketamine 28 mg	Participants will receive 28 mg esketamine as nasal spray (Initial dose for elderly participants with 65-74 years of age on Day 1 and then uptitrated to 56 mg on Day 4).
DRUG	Esketamine 56 mg	Participants will receive 56 mg esketamine as nasal spray (Initial dose for participants with 18-64 years of age) on Day 1. The dose may be increased/may remain same based on the efficacy and tolerability. Participants with 65 to 74 years of age will receive esketamine 56 mg from Day 4 onwards.
DRUG	Esketamine 84 mg	Participants may receive 84 mg (maximum uptitrated esketamine dose). The dose may be decreased/may remain same based on the efficacy and tolerability.
DRUG	Placebo	Participants will receive matching placebo as nasal spray.
DRUG	Escitalopram	Escitalopram can be selected as the oral antidepressant medication based on investigator's discretion. The initial dose for escitalopram is 5 mg once daily (for elderly participants) and 10 mg once daily (for adults). The dose may be increased to 10 mg (for elderly participants) and 20 mg (for adults) once daily at the discretion of treating physician/investigator.
DRUG	Sertraline	Sertraline can be selected as the oral antidepressant medication based on investigator's discretion. The initial dose for sertraline is 50 mg once daily and may be increased up to 200 mg once daily.
DRUG	Duloxetine	Duloxetine can be selected as the oral antidepressant medication based on investigator's discretion. The initial dose for duloxetine is 60 mg once daily and may be increased to 120 mg once daily.
DRUG	Mirtazapine	Mirtazapine can be selected as the oral antidepressant medication based on investigator's discretion. The initial dose for mirtazapine is 15 to 30 mg once daily and may be increased to 45 mg once daily.
DRUG	Agomelatine	Agomelatine can be selected as the oral antidepressant medication based on investigator's discretion. The initial dose for agomelatine is 25 mg once daily and may be increased to 50 mg once daily after 2 weeks.
DRUG	Bupropion	Bupropion can be selected as the oral antidepressant medication based on investigator's discretion. The initial dose for bupropion is 150 mg once daily and may be increased to 300 mg once daily after 4 weeks.
DRUG	Trazodone Prolonged Release	Trazodone prolonged release can be selected as the oral antidepressant medication based on investigator's discretion. The initial dose for trazodone prolonged release is 75 to 150 mg once or twice daily and may be increased up to 450 mg (adults) and 300 mg (elderly).

Timeline

• Start date: 2019-12-01
• Primary completion: 2021-07-25
• Completion: 2021-07-25
• First posted: 2019-02-25
• Last updated: 2025-04-27

Regulatory

• FDA-regulated drug study