Clinical Trial: A Long-term, Safety and Efficacy Study of Intranasal Esketamine in Treatment-resistant Depression
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: An Open-label, Long-term, Safety and Efficacy Study of Intranasal Esketamine in Treatment-resistant Depression
Brief Summary: The purpose of this open-label, multicenter study is to assess the long term safety and efficacy of intranasal esketamine plus an oral antidepressant 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), multicenter (more than 1 study site), long-term safety and efficacy study of intranasal esketamine plus an oral antidepressant in participants with treatment-resistant depression (TRD). Participants will enter the study either directly (direct-entry participants) or after completing the Double-Blind Induction Phase of ESKETINTRD3005 (transferred-entry participants). The study consists of 4 phases: Screening Phase (4 weeks), Open-Label Induction Phase (4 weeks), Open-Label Optimization/Maintenance phase (48 weeks), and Follow up Phase (4 weeks). Transferred entry non-responders in the ESKETINTRD3005 may enter study at the Open-Label Induction Phase and responders in the ESKETINTRD3005 may enter Optimization/Maintenance phase. In the Open-Label Induction Phase, participants will self-administer flexibly-dosed intranasal esketamine (participants who are less than (<) 65 years old self-administer 56 mg or 84 mg dose, participants who are greater than or equal to (>=) 65 years old self-administer 28 mg, 56 mg or 84 mg dose) twice weekly for 4 weeks. The starting dose for all participants >= 65 years old will be 28 mg. In addition, each direct-entry participants will be assigned to receive 1 of 4 selected oral antidepressant medications (escitalopram or sertraline or duloxetine or venlafaxine extended release [XR]), initiated on Day 1 of the open-label induction phase and continued through the duration of the study. Transferred-entry participants will continue their same antidepressant from ESKETINTRD3005 through the duration of this study. Participants who are responders at the end of the Open-Label Induction phase and transferred-entry responder participants (from study ESKETINTRD3005) will enter the Optimization/Maintenance Phase where intranasal esketamine treatment sessions will be reduced from that in the induction phase (twice weekly) to weekly for the
Sponsor: Janssen Research & Development, LLC
Current Primary Outcome:
- Change from baseline in Bladder Pain/ Interstitial Cystitis Symptom Score (BPIC-SS) score [ Time Frame: Baseline (Day 1) up to end of Follow Up phase (Week 56) ]Bladder Pain/ Interstitial Cystitis Symptom Score (BPIC-SS), is a scale to monitor for symptoms of cystitis, bladder pain, and interstitial cystitis.
- Change from baseline in Cogstate computerized cognitive battery domains and Hopkins Verbal Learning Test-Revised (HVLT-R) [ Time Frame: Baseline (Day 1) up to end of Follow Up phase (Week 56) ]The cognitive battery will provide assessment of multiple cognitive domains, including attention, visual learning and memory, and executive function. The HVLT-R is a measure of verbal learning and memory.
- Incidence of withdrawal symptoms assessed by Physician Withdrawal Checklist (PWC-20) [ Time Frame: Week 52 (end of optimization/maintenance phase) or Week 54 (week 2 of Follow Up phase) or Week 56 (week 4 of Follow Up phase) ]The PWC-20 is a 20-item questionnaire to assess potential development of discontinuation symptoms after stopping of study drug.
Original Primary Outcome:
- Change from baseline in Bladder Pain/ Interstitial Cystitis Symptom Score (BPIC-SS) score greater than (>)18 over time [ Time Frame: Baseline (Day 1) up to end of Follow Up phase (Week 56) ]Bladder Pain/ Interstitial Cystitis Symptom Score (BPIC-SS), is a scale to monitor for symptoms of cystitis, bladder pain, and interstitial cystitis.
- Change from baseline in Cogstate computerized cognitive battery domains and Hopkins Verbal Learning Test-Revised (HVLT-R) [ Time Frame: Baseline (Day 1) up to end of Follow Up phase (Week 56) ]The cognitive battery will provide assessment of multiple cognitive domains, including attention, visual learning and memory, and executive function. The HVLT-R is a measure of verbal learning and memory.
- Incidence of withdrawal symptoms assessed by Physician Withdrawal Checklist (PWC-20) [ Time Frame: Week 52 (end of optimization/maintenance phase) or Week 54 (week 2 of Follow Up phase) or Week 56 (week 4 of Follow Up phase) ]The PWC-20 is a 20-item questionnaire to assess potential development of discontinuation symptoms after stopping of study drug.
Current Secondary Outcome:
- Number of participants with Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Day 1 post dose through end of Follow Up Phase (Week 56) ]
- Change from baseline in Heart Rate [ Time Frame: Baseline of each dosing session (predose) up to the last post-dose measurement (40 minutes, 1 and 1.5 hours) from the start of Induction Phase to End of Optimization/Maintenance Phase (week 52) ]Change from baseline (predose) in heart rate will be assessed.
- Change from Baseline in systolic and diastolic blood pressure [ Time Frame: Baseline of each dosing session (predose) up to the last post-dose measurement (40 minutes, 1 and 1.5 hours) from the start of Induction Phase to End of Optimization/Maintenance Phase (week 52) ]Change From Baseline (predose) in systolic and diastolic blood pressure will be assessed.
- Change from Baseline in Respiratory rate [ Time Frame: Baseline of each dosing session (predose) up to the last post-dose measurement (40 minutes, 1 and 1.5 hours) from the start of Induction Phase to End of Optimization/Maintenance Phase (week 52) ]Change from Baseline in Respiratory rate (predose) 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 (1.5 hours or longer) from the start of Induction Phase to End of Optimization/Maintenance Phase (week 52) ]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: Baseline of each dosing session (predose),up to the last post dose measurement (1.5 hours or longer) from the start of Induction Phase to End of Optimization/Maintenance Phase (week 52) ]Effects on alertness and sedation are measured using Modified Observer's Assessment of Alertness/Sedation (MOAAS) scale.
- Change from Baseline in Brief Psychiatric Rating Scale Total Score [ Time Frame: Baseline of each dosing session (predose),up to the last post dose measurement (1.5 hours) from the start of Induction Phase to End of Optimization/Maintenance Phase (week 52) ]Potential psychosis-like effects are measured using Brief Psychiatric Rating Scale, positive-symptom subscale (BPRS+).
- Change from Baseline in Clinician-Administered Dissociative States Scale (CADSS) total score [ Time Frame: Baseline of each dosing session (predose) , up to the last post-dose measurement (1.5 hours) from the start of Induction Phase to End of Optimization/Maintenance Phase (week 52) ]Dissociative symptoms are assessed using CADSS.
- Change from Baseline in Columbia Suicide Severity Rating Scale (CSSRS) Score [ Time Frame: Baseline (Day 1) up to the End of Optimization/Maintenance Phase (week 52) ]Potential effects on suicidal ideation/behavior are evaluated with Columbia Suicide Severity Rating Scale (CSSRS).
- Change from Baseline in Nasal Tolerability [ Time Frame: Baseline of each dosing session (predose) to 1-hour post-dose from the start of Induction Phase to End of Optimization/Maintenance Phase (week 52) ]Nasal tolerability will be assessed by a Nasal Tolerability Questionnaire.
- Change from Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score [ Time Frame: Baseline up to End of Induction Phase (Day 28) and end of Optimization/Maintenance Phase (Week 52) ]The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment.
- Change from Baseline in Clinical Global Impression-Severity (CGI-S) score [ Time Frame: Baseline up to End of Optimization/Maintenance Phase (Week 52) ]The CGI-S evaluates the severity of psychopathology on a scale of 0 to 7.
- Change from Baseline in Subject-reported Depressive Symptoms Using the Patient Health Questionnaire - 9 (PHQ-9) Total Score [ Time Frame: Baseline up to End of Optimization/Maintenance Phase (Week 52) ]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 Subject-reported Generalized Anxiety Disorder (GAD-7) Score [ Time Frame: Baseline up to End of Optimization/Maintenance Phase (Week 52) ]The GAD-7 is a brief and validated measure of overall 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) [&nbs
Original Secondary Outcome: Same as current
Information By: Janssen Research & Development, LLC
Dates:
Date Received: May 18, 2015
Date Started: September 30, 2015
Date Completion: April 30, 2018
Last Updated: May 8, 2017
Last Verified: May 2017