A Study to Evaluate the Safety and Efficacy of Intranasal Esketamine in Treatment-resistant Depression
Condition: Treatment Resistant Depressive Disorder
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant
Intervention: Esketamine 14 mg; Esketamine 28 mg; Esketamine 56 mg; Esketamine 84 mg; Placebo
Intervention description: 1 to 6 sprays of esketamine 14 mg self-administered as an intranasal formulation for 4 days (Days 1, 4, 8, 11) during the double-blind phase and if applicable during the optional open-label phase for up to 4 days; 1 to 6 sprays of esketamine 28 mg self-administered as an intranasal formulation for 4 days (Days 1,4, 8, 11) during the double-blind phase and if applicable, during the optional open-label phase for up to 9 days; 1 to 6 sprays of esketamine 56 mg self-administered as an intranasal formulation for up to 4 days (Days 1, 4, 8, 11) during the double-blind phase and if applicable, during the optional open-label phase for up to 9 days; 1 to 6 sprays of esketamine 84 mg self-administered as an intranasal formulation for up to 4 days (Days 1, 4, 8, 11) during the double-blind phase and if applicable, during the optional open-label phase for up to 9 days; 1 to 6 sprays of placebo self-administered as an intranasal formulation for 2 days (Days 1 and 4) or depending on response on Day 8, for 4 days (Days 1,4, 8, 11) during the double-blind phase
Intervention MeSH terms: Esketamine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 108.0
Sex: All
Minimum age: 20 Years
Maximum age: 64 Years
Healthy volunteers: No
Keywords: Treatment resistant depressive disorder; Intranasal esketamine; Efficacy; SYNAPSE; JNJ-54135419

Summary:

      The purpose of this study is to assess the efficacy and dose response of intranasal
      esketamine (Panel A: 28 mg, 56 mg, and 84 mg and Panel B: 14 mg and 56 mg) compared with
      placebo in improving depressive symptoms in participants with treatment-resistant depression
      (TRD).
    

Eligibility criteria:

        Inclusion Criteria:

        --Participant must meet Diagnostic and Statistical Manual of Mental Disorders -Fourth
        Edition -Text Revised (DSM-IV-TR) diagnostic criteria for Major Depressive Disorder (MDD),
        without psychotic features, based upon clinical assessment, and confirmed by the Mini
        International Neuropsychiatric Interview (MINI)-Participant's major depressive episode and
        treatment response must be deemed "valid" by remote independent raters-Participant must
        have had an inadequate response to at least 2 antidepressants, at least one of which is in
        the current episode of depression; the antidepressant treatment response questionnaire
        (ATRQ) will be used to assess antidepressant treatment response during the current episode;
        prior medication history will be used to determine antidepressant treatment response in
        prior episode(s) -Have an Inventory of Depressive Symptoms-Clinician rated, 30-item
        (IDS-C30) total score >=34 at Screening and predose at Day 1

        Exclusion Criteria:

        -Participant has a current DSM-IV-TR diagnosis of bipolar and related disorders,
        intellectual disability, or cluster b personality disorder (e.g., borderline personality
        disorder, antisocial personality disorder, histrionic personality disorder, and
        narcissistic personality disorder) -Participant has a current or prior DSM-IV-TR diagnosis
        of a psychotic disorder, MDD with psychosis, post-traumatic stress disorder (PTSD), or
        obsessive compulsive disorder (OCD) -Anatomical or medical conditions that may impede
        delivery or absorption of study medication (e.g., undergone facial reconstruction,
        rhinoplasty, significant structural or functional abnormalities of the nose or upper
        airway; obstructions or mucosal lesions of the nostrils or nasal passages; undergone sinus
        surgery in the previous 2 years; signs and symptoms of rhinitis) -Has an abnormal or
        deviated nasal septum with any 1 or more of the following symptoms: blockage of 1 or both
        nostrils, nasal congestion (especially 1-sided), frequent nosebleeds, frequent sinus
        infections, and at times has facial pain, headaches, and postnasal drip -Has a history of
        substance abuse (drug or alcohol) or dependence (except nicotine or caffeine) within the
        previous 1 year of the screening visit -Participant has known allergies, hypersensitivity,
        intolerance, or contraindication to esketamine/ketamine or its excipients