Clinical Trial: A Study to Evaluate the Efficacy, Safety, and Tolerability of Flexible Doses of Intranasal Esketamine Plus an Oral Antidepressant 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 to Evaluate the Efficacy, Safety, and Tolerability of Flexible Doses of Intranasal Esketamine Plus an Oral Antidepressant in Adult Subj

Brief Summary: The purpose of this study is to compare the efficacy and safety of switching treatment-resistant depression (TRD) subjects from a prior antidepressant treatment (to which they have not responded) to either intranasal esketamine plus a new oral antidepressant or switching to a new oral antidepressant plus intranasal placebo.

Detailed Summary: This is a randomized, double-blind (neither the researchers nor the subjects know what treatment the subject is receiving), active-controlled, multicenter study (more than 1 study site) in subjects with TRD to assess the efficacy, safety, and tolerability of flexible doses of intranasal esketamine plus a newly initiated oral antidepressant compared with a newly initiated oral antidepressant (active comparator) plus intranasal placebo. The study will consist of 3 phases: Screening/Prospective Observational Phase (4-7 weeks), Double-blind Induction Phase (4-weeks), Follow-up Phase (24-weeks). Subjects who rollover into a long-term maintenance study will not participate in the Follow-up Phase. The antidepressant treatment, as well as any other ongoing medications being taken for depression at screening (including adjunctive/ augmentation therapies), will continue unchanged, at the same dosage, from the start of Week 1 through the end of Week 4 of the screening/prospective observational phase. Subjects' safety will be monitored throughout the study.
Sponsor: Janssen Research & Development, LLC

Current Primary Outcome: Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at End of Double-blind Induction Phase [ Time Frame: Baseline and End of Double-blind Induction Phase (Week 4) ]

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, inability to feel (interest level), pessimistic thoughts, and suicidal thoughts.


Original Primary Outcome: Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at End of Double-blind Induction Phase [ Time Frame: Baseline and End of Double-blind Induction Phase (Week 4) ]

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:

  • Change From Baseline in Subject-reported Depressive Symptoms Using the Patient Health Questionnaire-9 (PHQ-9) Total Score at End of Double-blind Induction Phase [ Time Frame: Baseline and End of Double-blind Induction Phase (Week 4) ]
    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 Subject-reported Functioning and Associated Disability as assessed by the Sheehan Disability Scale (SDS) Total Score at End of Double-blind Induction Phase [ Time Frame: Baseline and End of Double-blind Induction Phase (Week 4) ]
    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.
  • Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at End of Double-blind Induction Phase [ Time Frame: Baseline and End of Double-blind Induction Phase (Week 4) ]
    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) Total Score at End of Double-blind Induction Phase [ Time Frame: Baseline and End of Double-blind Induction Phase (Week 4) ]
    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 Double-blind Induction Phase [ Time Frame: Baseline and End of Double-blind Induction Phase (Week 4) ]
    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.
  • Number of Participants with Adverse Events (AEs) and Serious AEs [ Time Frame: Screening up to End of Follow-up Phase (approximately up to 32 - 35 weeks) ]
    An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
  • Onset of Clinical Response That Continued Through the End of the 4-Week Double-blind Induction Phase [ Time Frame: Day 2 through the End of Double-Blind Induction Phase (Week 4) ]
    Onset of Clinical Response is defined as greater than or equal to (>=) 50% improvement in MADRS total score by the day after taking the first dose [ie, Day 2] of double blind intranasal medication, that is sustained through the end of the 4-week double-blind induction phase.


Original Secondary Outcome: Same as current

Information By: Janssen Research & Development, LLC

Dates:
Date Received: April 13, 2015
Date Started: August 7, 2015
Date Completion: January 15, 2018
Last Updated: April 21, 2017
Last Verified: April 2017