Clinical Trial: A Study of Intranasal Esketamine Plus an Oral Antidepressant for Relapse Prevention in Adult Participants With Treatment-resistant Depression

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Randomized, Double-blind, Multicenter, Active-Controlled Study of Intranasal Esketamine Plus an Oral Antidepressant for Relapse Prevention in Treatment-resistant Depression

Brief Summary: The purpose of this study is to assess the efficacy of intranasal esketamine plus an oral antidepressant compared with an oral antidepressant (active comparator) plus intranasal placebo in delaying relapse of depressive symptoms in participants with treatment-resistant depression (TRD) who are in stable remission after an induction and optimization course of intranasal esketamine plus an oral antidepressant.

Detailed Summary: This is a randomized, double-blind (neither the researchers nor the participant know what treatment the participants is receiving), active-controlled, multicenter (more than 1 study site) study in participants with TRD to assess the efficacy of intranasal esketamine plus an oral antidepressant compared with an oral antidepressant (active comparator) plus intranasal placebo in delaying relapse of depressive symptoms. The study will consist of 5 phases: Screening/Prospective Observational Phase (4-7weeks) for direct-entry participants only, Open-label Induction Phase (4-weeks) for direct-entry participants only, Optimization Phase (12-weeks; open-label for direct-entry participants and double-blind for transferred-entry participants), Maintenance Phase (variable duration; double-blind for all participants) and Follow-up Phase (2-weeks). Participants' safety will be monitored throughout the study.
Sponsor: Janssen Research & Development, LLC

Current Primary Outcome: Time to relapse in Participants with stable remission who were randomized in the maintenance phase [ Time Frame: Time between participant randomization into the maintenance phase and the first documentation of a relapse event (up to an anticipated maximum of 104 weeks) ]

Relapse is defined as any of the following: (1) MADRS total score greater than or equal to 22 for 2 consecutive assessments separated by 5 to 15 days (inclusive); or (2) Hospitalization for worsening depression or any other clinically relevant event determined per clinical judgment to be suggestive of a relapse of depressive illness such as suicide attempt, completed suicide, or hospitalization for suicide prevention. If hospitalized for any of these events, the start date of hospitalization will be used for the date of relapse. Otherwise the date of the event will be used if the participant is not hospitalized.


Original Primary Outcome: Time to relapse in Participants with stable remission who were randomized in the maintenance phase [ Time Frame: Time between participant randomization into the maintenance phase and the first documentation of a relapse event (up to an anticipated maximum of 104 weeks) ]

Relapse is defined as any of the following: (1) MADRS total score ≥ 22 for 2 consecutive assessments separated by 5 to 15 days (inclusive); or (2) Hospitalization for worsening depression, for a suicide attempt, or for suicide prevention. The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition. The MADRS evaluates apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts.


Current Secondary Outcome:

  • Time to relapse in Participants with Stable Response (but not in stable remission) who were randomized in the maintenance phase [ Time Frame: Time between participant randomization into the maintenance phase and the first documentation of a relapse event (up to an anticipated maximum of 104 weeks) ]
    Refer to relapse and MADRS descriptions above.
  • Change From Baseline in MADRS total score at end of the Maintenance Phase in participants who were randomized in this phase [ Time Frame: Baseline and End of Maintenanace Phase (up to an anticipated maximum of 104 weeks) ]
    The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition. The MADRS evaluates apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts.
  • Change From Baseline in Subject-reported Depressive Symptoms Using the Patient Health Questionnaire-9 (PHQ-9) Total Score at End of the Maintenance Phase in participants who were randomized in this phase [ Time Frame: Baseline and End of Maintenance Phase (up to an anticipated maximum of 104 weeks) ]
    The PHQ-9 is a 9-item scale used to assess depressive symptoms. Each item is rated on a 4-point scale (0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day). The responses for each item are summed to provide a total score (range of 0 to 27) with higher scores indicating greater severity of depressive symptoms.
  • Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at End of Maintenance Phase in participants who were randomized in this phase [ Time Frame: Baseline and End of Maintenance Phase (up to an anticipated maximum of 104 weeks) ]
    The CGI-S evaluates the severity of psychopathology on a scale of 0 to 7. Considering total clinical experience, a participant is assessed on severity of mental illness at the time of rating according to: 0=not assessed; 1=normal (not at all ill); 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients. The CGI-S permits a global evaluation of the participant's condition at a given time.
  • Change From Baseline in Subject-reported Generalized Anxiety Disorder (GAD-7) Score at End of Maintenance Phase in participants who were randomized in this phase [ Time Frame: Baseline and End of Maintenance Phase (up to an anticipated maximum of 104 weeks) ]
    The GAD-7 is a brief and validated measure of overall anxiety. Each item is rated on a 4-point scale (0=not at all; 1=several days; 2=more than half the days; and 3=nearly every day). Item responses are summed to yield a total score with range of 0 to 21, where higher scores indicate more anxiety.
  • Change From Baseline in Subject-reported Health-related Quality of Life and Health Status as Assessed by EuroQol-5 Dimension-5 Level (EQ-5D-5L) at End of Maintenance Phase in participants who were randomized in this phase [ Time Frame: Baseline and End of Maintenance Phase (up to an anticipated maximum of 104 weeks) ]
    The EQ-5D-5L is a standardized instrument for use as a measure of health outcome, primarily designed for self-completion by respondents. It consists of the EQ-5D-5L descriptive system and the EQ visual analogue scale (EQ-VAS). The EQ-5D-5L descriptive system comprises the following 5 dimensions: Mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each of the 5 dimensions is divided into 5 levels of perceived problems (Level 1 indicating no problem, Level 2 indicating slight problems, Level 3 indicating moderate problems, Level 4 indicating severe problems, and Level 5 indicating extreme problems). The participant selects an answer for each of the 5 dimensions considering the response that best matches his or her health "today." The descriptive system can be represented as a health state. The EQ-VAS self-rating records the respondent's own assessment of his or her overall health status at the time of completion, on a scale of 0 to 100.
  • Change From Baseline in Sheehan Disability Scale (SDS) Total Score at End of Maintenance Phase in participants who were randomized in this phase [ Time Frame: Baseline and End of Maintenance Phase (up to an anticipated maximum of 104 weeks) ]
    The SDS is a subject-reported outcome measure and is a 5-item questionnaire which has been widely used and accepted for assessment of functional impairment and associated disability. The first three items assess disruption of (1) work/school, (2) social life, and (3) family life/home responsibilities using a 0-10 rating scale. The score for the first three items are summed to create a total score of 0-30 where a higher score indicates greater impairment.
  • Number of Participants with Adverse Events (AEs) and Serious AEs [ Time Frame: Screening up to End of Follow-up Phase (after the last clinic v

    Original Secondary Outcome:

    • Time to relapse in Participants with Stable Response (but not in stable remission) who were randomized in the maintenance phase [ Time Frame: Time between participant randomization into the maintenance phase and the first documentation of a relapse event (up to an anticipated maximum of 104 weeks) ]
      Refer to relapse and MADRS descriptions above.
    • Change From Baseline in MADRS total score at end of the Maintenance Phase in participants who were randomized in this phase [ Time Frame: Baseline and End of Maintenanace Phase (up to an anticipated maximum of 104 weeks) ]
      The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition. The MADRS evaluates apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts.
    • Change From Baseline in Subject-reported Depressive Symptoms Using the Patient Health Questionnaire-9 (PHQ-9) Total Score at End of the Maintenance Phase in participants who were randomized in this phase [ Time Frame: Baseline and End of Maintenance Phase (up to an anticipated maximum of 104 weeks) ]
      The PHQ-9 is a 9-item scale used to assess depressive symptoms. Each item is rated on a 4-point scale (0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day). The responses for each item are summed to provide a total score (range of 0 to 27) with higher scores indicating greater severity of depressive symptoms.
    • Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at End of Maintenance Phase in participants who were randomized in this phase [ Time Frame: Baseline and End of Maintenance Phase (up to an anticipated maximum of 104 weeks) ]
      The CGI-S evaluates the severity of psychopathology on a scale of 0 to 7. Considering total clinical experience, a participant is assessed on severity of mental illness at the time of rating according to: 0=not assessed; 1=normal (not at all ill); 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients. The CGI-S permits a global evaluation of the participant's condition at a given time.
    • Change From Baseline in Subject-reported Generalized Anxiety Disorder (GAD-7) Score at End of Maintenance Phase in participants who were randomized in this phase [ Time Frame: Baseline and End of Maintenance Phase (up to an anticipated maximum of 104 weeks) ]
      The GAD-7 is a brief and validated measure of overall anxiety. Each item is rated on a 4-point scale (0=not at all; 1=several days; 2=more than half the days; and 3=nearly every day). Item responses are summed to yield a total score with range of 0 to 21, where higher scores indicate more anxiety.
    • Change From Baseline in Subject-reported Health-related Quality of Life and Health Status as Assessed by EuroQol-5 Dimension-5 Level (EQ-5D-5L) at End of Maintenance Phase in participants who were randomized in this phase [ Time Frame: Baseline and End of Maintenance Phase (up to an anticipated maximum of 104 weeks) ]
      The EQ-5D-5L is a standardized instrument for use as a measure of health outcome, primarily designed for self-completion by respondents. It consists of the EQ-5D-5L descriptive system and the EQ visual analogue scale (EQ-VAS). The EQ-5D-5L descriptive system comprises the following 5 dimensions: Mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each of the 5 dimensions is divided into 5 levels of perceived problems (Level 1 indicating no problem, Level 2 indicating slight problems, Level 3 indicating moderate problems, Level 4 indicating severe problems, and Level 5 indicating extreme problems). The participant selects an answer for each of the 5 dimensions considering the response that best matches his or her health "today." The descriptive system can be represented as a health state. The EQ-VAS self-rating records the respondent's own assessment of his or her overall health status at the time of completion, on a scale of 0 to 100.
    • Change From Baseline in Sheehan Disability Scale (SDS) Total Score at End of Maintenance Phase in participants who were randomized in this phase [ Time Frame: Baseline and End of Maintenance Phase (up to an anticipated maximum of 104 weeks) ]
      The SDS is a subject-reported outcome measure and is a 5-item questionnaire which has been widely used and accepted for assessment of functional impairment and associated disability. The first three items assess disruption of (1) work/school, (2) social life, and (3) family life/home responsibilities using a 0-10 rating scale. The score for the first three items are summed to create a total score of 0-30 where a higher score indicates greater impairment.
    • Number of Participants with Adverse Events (AEs) and Serious AEs [ Time Frame: Screening up to End of Follow-up Phase (up to 2 weeks after las

      Information By: Janssen Research & Development, LLC

      Dates:
      Date Received: May 13, 2015
      Date Started: October 1, 2015
      Date Completion: April 30, 2018
      Last Updated: May 8, 2017
      Last Verified: May 2017