NCT04338321

A Long-term Comparison of Esketamine Nasal Spray Versus Quetiapine Extended Release, Both in Combination With a Selective Serotonin Reuptake Inhibitor/Serotonin-Norepinephrine Reuptake Inhibitor, in Participants With Treatment Resistant Major Depressive Disorder

A Randomized, Open-label, Rater-Blinded, Active-Controlled, International, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of Flexibly Dosed Esketamine Nasal Spray Compared With Quetiapine Extended-Release in Adult and Elderly Participants With Treatment-Resistant Major Depressive Disorder Who Are Continuing a Selective Serotonin Reuptake Inhibitor/Serotonin-Norepinephrine Reuptake Inhibitor

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 676 (actual)
• Sponsor: Janssen-Cilag International NV · Industry
• Sex: All
• Age: 18 Years – 74 Years
• Healthy volunteers: Not accepted

Summary

The primary purpose of this study is to evaluate the efficacy of flexibly dosed esketamine nasal spray compared with quetiapine extended-release (XR), both in combination with a continuing selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI), in achieving remission in participants who have treatment-resistant major depressive disorder (MDD) with a current moderate to severe depressive episode.

Detailed description

A depressive state with classical symptoms such as low (depressive/sad) mood, markedly diminished interest in activities, significant weight loss/gain, insomnia or hypersomnia, psychomotor agitation/retardation, excessive fatigue, inappropriate guilt, diminished concentration, and recurrent thoughts of death, persisting for more than 2 weeks is classified as major depressive disorder (MDD). The mechanism of action of ketamine is distinct from conventional antidepressants (ADs), which target the monoamines (serotonin, norepinephrine, and/or dopamine). Esketamine, the S-enantiomer of ketamine, is approved and widely used for the induction and maintenance of anesthesia via intramuscular or intravenous (IV) administration. There is a significant unmet need to develop novel AD treatments based on the relevant psychophysiological pathways underlying MDD. The goal of any novel treatment would be the rapid and long-lasting relief of depressive symptoms, especially in participants with treatment-resistant depression (TRD), who lack a sufficient response to the currently available treatment strategies. The study consists of a Screening Phase (up to 14 days), an Acute Phase (8 Weeks), a Maintenance Phase (24 Weeks) and a Safety Follow-up Phase (2 Weeks). Safety assessment includes adverse event, serious adverse events, physical examination, vital signs, electrocardiogram, clinical safety laboratory assessments, suicidal risk monitoring. The total duration of the study is approximately 36 Weeks for all participants.

Conditions

• Depressive Disorder, Major

Interventions

Type	Name	Description
DRUG	Esketamine 28 mg	Esketamine will be self-administered at a dose of 28 mg as nasal spray.
DRUG	Esketamine 56 mg	Esketamine will be self-administered at a dose of 56 mg as nasal spray.
DRUG	Esketamine 84 mg	Esketamine will be self-administered at a dose of 84 mg (maximum uptitrated dose) as nasal spray.
DRUG	Quetiapine XR 50 mg	Quetiapine XR will be administered at an initial dose of 50 mg/day and may be further increased to 300 mg/day based on individual participant evaluation.
DRUG	Quetiapine XR 100 mg	Quetiapine XR will be administered at a dose of 100 mg/day and may be further increased to 300 mg/day based on individual participant evaluation.
DRUG	Quetiapine XR 150 mg	Quetiapine XR will be administered at a dose of 150 mg/day and may be further increased to 300 mg/day based on individual participant evaluation.
DRUG	SSRI/SNRI	Participants will continue to take SSRI/SNRI that is approved for use in depression in their country of participation; off-label use of any SSRI/SNRI is not permitted. The continuing SSRI/SNRI dosage may be optimized throughout the study, at the investigator's discretion and based on the SmPC (or local equivalent, if applicable).

Timeline

• Start date: 2020-08-21
• Primary completion: 2022-01-20
• Completion: 2022-07-15
• First posted: 2020-04-08
• Last updated: 2025-04-29
• Results posted: 2023-02-15

Locations

171 sites across 24 countries: Argentina, Austria, Belgium, Brazil, Bulgaria, Czechia, Denmark, Finland, Germany, Greece, Hungary, Israel, Kazakhstan, Malaysia, Netherlands, Norway, Poland, Portugal, South Africa, South Korea, Sweden, Taiwan, Turkey (Türkiye), United Arab Emirates

Regulatory

• FDA-regulated drug study