Clinical Trial: A Long-term Safety Study of Intranasal Esketamine in Treatment-resistant Depression

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

Official Title: An Open-label Long-term Extension Safety Study of Intranasal Esketamine in Treatment-resistant Depression

Brief Summary: The purpose of this study is to assess the safety and tolerability of intranasal esketamine in participants with treatment-resistant depression (TRD).

Detailed Summary: This is an open-label (the researchers and participants know the treatment the participant is receiving) long-term extension study. The study will consist of 2 open-label Phases: 4-week Induction phase (if applicable) and Open-Label Optimization/Maintenance phase (variable). Participants will enter the study Induction Phase from ESKETINTRD3001 (NCT02417064), ESKETINTRD3002 (NCT02418585), ESKETINTRD3003 (NCT02493868), ESKETINTRD3005 (NCT02422186) and ESKETINTRD3006 (US sites only). Participants will enter the study Open-Label Optimization/Maintenance phase from ESKETINTRD3001 (NCT02417064), ESKETINTRD3002 (NCT02418585), ESKETINTRD3003 (NCT02493868) (if appropriate at week 16) or ESKETINTRD3006 (US sites only). In the Open-Label Induction Phase, participants will self-administer flexibly-dosed intranasal esketamine. During first 4 weeks in Optimization/Maintenance Phase responder participants from the induction phase of study 54135419TRD3008, will continue on the same dose of intranasal esketamine from the induction phase and have a weekly intranasal treatment session frequency. Participants entering the optimization/maintenance phase from study ESKETINTRD3005 will also have a weekly intranasal treatment session frequency. However, as the ESKETINTRD3005 intranasal study medication is blinded at the time of entry into the current study, the dose of intranasal esketamine will be administered as outlined in protocol. Participants entering the optimization/maintenance phase from study ESKETINTRD3003 (Direct Entry) or ESKETINTRD3004 who were ongoing in the Optimization, Maintenance, or Optimization/Maintenance phase, respectively, will have the option to have their current intranasal dosing frequency adjusted at the time of entry into 54135419TRD3008 study and should remain on the selected frequency from week 1 to week 4. A one-time dose change will be permitted at study entry. After 4 weeks, intranasal esketamine treatment sessions will be individualized to either once we
Sponsor: Janssen Research & Development, LLC

Current Primary Outcome:

  • Number of Participants With Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Up to End of Study (approximately 5 years 3 months) ]
  • Change From Baseline in Systolic and Diastolic Blood Pressure [ Time Frame: Baseline of each dosing session (predose) up to the last post-dose measurement from the start of Induction Phase to End of Optimization/Maintenance Phase (approximately 5 years 3 months) ]
    Change From Baseline (predose) in systolic and diastolic blood pressure will be assessed.
  • Change From Baseline in Heart Rate [ Time Frame: Baseline of each dosing session (predose) up to the last post-dose measurement from the start of Induction Phase to End of Optimization/Maintenance Phase (approximately 5 years 3 months) ]
    Change from Baseline (predose) in heart rate will be assessed.
  • Change From Baseline in Blood Oxygen Saturation [ Time Frame: Baseline of each dosing session (predose) up to the last post-dose measurement from the start of Induction Phase to End of Optimization/Maintenance Phase (approximately 5 years 3 months) ]
    Change From Baseline in Blood oxygen saturation (predose) will be assessed.
  • Change From Baseline in Modified Observer's Assessment of Alertness/Sedation (MOAAS) Scale Score [ Time Frame: 1 hour post-dose from the start of Induction Phase to End of Optimization/Maintenance Phase (approximately 5 years 3 months) ]

    The MOAA/S will be used to measure treatment-emergent sedation, with correlation to le

    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Change From Baseline in Participant-Reported Depressive Symptoms Using the Patient Health Questionnaire - 9 (PHQ-9) Total Score [ Time Frame: From the start of Induction Phase to End of Optimization/Maintenance Phase (approximately 5 years 3 months) ]
      The PHQ-9 is a 9-item scale used to assess depressive symptoms. 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 [ Time Frame: From the start of Induction Phase to End of Optimization/Maintenance Phase (approximately 5 years 3 months) ]
      The CGI-S evaluates the severity of psychopathology on a scale of 0 to 7.
    • Change From Baseline in days when participants assess disruption of (1) work/school, (2) social life, leisure activities, and (3) family life/home responsibilities as Assessed by the Sheehan Disability Scale (SDS) Total Score [ Time Frame: From the start of Induction Phase to End of Optimization/Maintenance Phase (approximately 5 years 3 months) ]
      The SDS, a patient-reported outcome measure, is a 5 item questionnaire which has been widely used and accepted for assessment of functional and associated disability impairment. 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. It also has one item on days lost from school or work and one item on days when underproductive.
    • Change From Baseline in days symptoms caused participants to miss school or work or were unable to carry out normal daily responsibilitieswhen participant lost from school or work as as Assessed by the Sheehan Disability Scale (SDS) [ Time Frame: From the start of Induction Phase to End of Optimization/Maintenance Phase (approximately 5 years 3 months) ]
      The SDS, a patient-reported outcome measure, is a 5 item questionnaire which has been widely used and accepted for assessment of functional 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. It also has one item on days lost from school or work and one item on days when underproductive.
    • Change From Baseline in days when participant was underproductive as Assessed by the Sheehan Disability Scale (SDS) [ Time Frame: From the start of Induction Phase to End of Optimization/Maintenance Phase (approximately 5 years 3 months) ]
      The SDS, a patient-reported outcome measure, is a 5 item questionnaire which has been widely used and accepted for assessment of functional 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. It also has one item on days lost from school or work and one item on days when underproductive.
    • Change From Baseline in Participant-Reported Health-related Quality of Life as Assessed by EuroQol-5 Dimension-5 Level (EQ-5D-5L) ) Valuation Index Score [ Time Frame: From the start of Induction Phase to End of Optimization/Maintenance Phase (approximately 5 years 3 months) ]
      The EQ-5D questionnaire is a brief, generic health-related quality of life assessment (HRQOL) that can also be used to incorporate participant preferences into health economic evaluations. The EQ-5D-5L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression and as overall health using a "thermometer" visual analog scale with response options ranging from 0 (worst imaginable health) to 100 (best imaginable health). Lower scores indicate worsening. EQ-5D scores include EQ-5D valuation index score (a weighted scoring of the 5 dimension scores with a possible range from 0 to 1) and EQ5D descriptive system scores (five scores reflecting each of the 5 EQ-5D health dimensions ranging from 0 [no limitation] to 4 [incapacity]).
    • Change From Baseline in Participant-Reported Health Status as Assessed by EuroQol-5 Dimension-5 Level (EQ-5D-5L) Visual Analog Scale (VAS) [ Time Frame: From the start of Induction Phase to End of Optimization/Maintenance Phase (approximately 5 years 3 months) ]
      EQ-5D visual analog scale (VAS) is a 20 centimeter (cm) vertical VAS with scores ranging from 0 (worst imaginable health) to 100 (perfect health. A higher score indicates an improvement in health in the Health Status Index. The EuroQol-5 is a five dimensional health state classification. Each dimension is assessed on a 3-point ordinal scale (1=no problems, 2=some problems, 3=extreme problems). The responses to the five EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D health status index score between 0 to 1, with 1.00 i

      Original Secondary Outcome: Same as current

      Information By: Janssen Research & Development, LLC

      Dates:
      Date Received: April 29, 2016
      Date Started: June 9, 2016
      Date Completion: December 31, 2024
      Last Updated: May 8, 2017
      Last Verified: May 2017