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
Condition: Depressive Disorder, Major
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): Esketamine 28 mg; Esketamine 56 mg; Esketamine 84 mg; Quetiapine XR 50 mg; Quetiapine XR 100 mg; Quetiapine XR 150 mg; SSRI/SNRI
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Esketamine will be self-administered at a dose of 28 mg as nasal spray.; Esketamine will be self-administered at a dose of 56 mg as nasal spray.; Esketamine will be self-administered at a dose of 84 mg (maximum uptitrated dose) as nasal spray.; 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.; 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.; 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.; 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).
Intervention MeSH terms: Quetiapine Fumarate; Esketamine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment