We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Long-term, Safety and Efficacy Study of Intranasal Esketamine in Treatment-resistant Depression (SUSTAIN-2)

This study is currently recruiting participants.
Verified October 2017 by Janssen Research & Development, LLC
Sponsor:
ClinicalTrials.gov Identifier:
NCT02497287
First Posted: July 14, 2015
Last Update Posted: October 24, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Janssen Research & Development, LLC
  Purpose
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).

Condition Intervention Phase
Treatment-resistant Depression Drug: Esketamine (Intranasal Spray) Drug: Duloxetine (Oral Antidepressant) Drug: Escitalopram (Oral Antidepressant) Drug: Sertraline (Oral Antidepressant) Drug: Venlafaxine Extended Release (XR) (Oral Antidepressant) Phase 3

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Long-term, Safety and Efficacy Study of Intranasal Esketamine in Treatment-resistant Depression

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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) [ Time Frame: Baseline up to End of Optimization/Maintenance Phase (Week 52) ]
    The EQ-5D-5L is a standardized instrument for use as a measure of health outcome. 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. 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 Subject-reported Functioning and Associated Disability as Assessed by the Sheehan Disability Scale (SDS) Total Score [ Time Frame: Baseline up to End of Optimization/Maintenance Phase (Week 52) ]
    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.

  • Percentage of participants with Response [ Time Frame: Baseline (Day 1) of Induction Phase up to End of Optimization/Maintenance Phase (Week 52 ) ]
    Percentage of participants with greater than or equal to (>=) 50% reduction from baseline (induction phase) in the MADRS total score and PHQ 9 total score will be reported.

  • Percentage of participants with Remission [ Time Frame: Baseline (Day 1) of Induction Phase up to End of Optimization/Maintenance Phase (Week 52 ) ]
    Percentage of participants with MADRS total score less than or equal to (<=) 12 will be reported.


Other Outcome Measures:
  • Change from baseline in hematology, biochemistry and urinalysis parameters [ Time Frame: Baseline to Follow up (week 56) ]
    Safety parameters

  • Change from Baseline in Electrocardiogram (ECG) intervals [ Time Frame: Baseline up to the last post-dose measurement (1 hour) from the start of Induction Phase to End of Optimization/Maintenance Phase (week 52) ]
    Safety parameters

  • Number of participants with suicidal ideations with some intent to act based on Columbia Suicide Severity Rating Scale (CSSRS) [ Time Frame: Baseline (Day 1) up to End of Optimization/Maintenance Phase (week 52) ]
    Potential effects on suicidal ideation/behavior are evaluated with Columbia Suicide Severity Rating Scale (CSSRS).


Estimated Enrollment: 750
Actual Study Start Date: September 30, 2015
Estimated Study Completion Date: October 31, 2017
Estimated Primary Completion Date: October 31, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intranasal Esketamine plus oral antidepressant
Open-Label Induction Phase: Participants will self-administer esketamine intranasally twice per week for 4 weeks as a flexible dose regimen (56 mg or 84 mg). Participants greater than or equal to (>=) 65 will start at a dose of 28 mg on Day 1. Direct-entry participants will initiate a new, open-label oral antidepressant (duloxetine, escitalopram, sertraline, or venlafaxine extended release [XR]) on Day 1; transferred-entry participants will continue the same oral antidepressant from ESKETINTRD3005. Optimization/Maintenance Phase: Participants will self-administer esketamine (56mg or 84mg for those < 65 years; 28 mg, 56 mg or 84 mg for those >= 65 years) intranasally once per week for 4 weeks; transferred entry responder subjects from ESKETINTRD3005 will start at a dose of 28 mg in the first week. All participants will continue their same oral antidepressant during this phase.
Drug: Esketamine (Intranasal Spray)
Open-Label Induction Phase: Participants will self-administer esketamine intranasally twice per week for 4 weeks as a flexible dose regimen (56 mg or 84 mg for those < 65 years; 28 mg, 56 mg or 84 mg for those >= 65 years). Participants >= 65 years old will start at a dose of 28 mg on Day 1. Optimization/Maintenance Phase: Participants will self-administer esketamine intranasally (56 mg or 84 mg for those < 65 years; 28 mg, 56 mg or 84 mg for those >= 65 years) once weekly then individualized to either once weekly or once every other week based on the severity of depressive symptoms. Transferred-entry responder participants from ESKETINTRD3005 >= 65 years old will start at a dose of 28 mg in Week 5.
Drug: Duloxetine (Oral Antidepressant)
Duloxetine could be selected as the oral antidepressant medication by the investigator based on review of Massachusetts General Hospital - Antidepressant Treatment Response Questionnaire (MGH-ATRQ) and relevant prior antidepressant medication information. The minimum therapeutic dose is 60 milligram per day (mg/day).
Drug: Escitalopram (Oral Antidepressant)
Escitalopram could be selected as the oral antidepressant medication by the investigator based on review of MGH-ATRQ and relevant prior antidepressant medication information. The minimum therapeutic dose is 10 mg/day. Participants >= 65 years of age will be titrated up to 20 mg/day, but can lower the dose to 10 mg/day for tolerability.
Drug: Sertraline (Oral Antidepressant)
Sertraline could be selected as the oral antidepressant medication by the investigator based on review of MGH-ATRQ and relevant prior antidepressant medication information. Sertraline will be titrated up to a dose of 150 mg/day, but if not tolerated the dose can be reduced to the minimum therapeutic dose of 50 mg/day.
Drug: Venlafaxine Extended Release (XR) (Oral Antidepressant)
Venlafaxine Extended Release could be selected as the oral antidepressant medication by the investigator based on review of MGH-ATRQ and relevant prior antidepressant medication information. Venlafaxine Extended Release will be titrated for participants < 65 years of age up to a dose of 225 mg/day, but if not tolerated the dose can be reduced to the minimum therapeutic dose of 150 mg/day. For participants >= 65, it can be titrated up to a dose of 150 mg/day, but if not tolerated the dose can be reduced to the minimum therapeutic dose of 75 mg/day.

Detailed Description:
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 first 4 weeks of this phase, and then individualized to either once weekly or once every other week based on the severity of depressive symptoms. Participants' safety and depressive symptoms will be assessed and monitored throughout the study.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

A). For Direct-Entry Participants

  • At the time of signing the informed consent form (ICF), participant must be a man or woman ≥18 (or older if the minimum legal age of consent in the country in which the study is taking place is greater than [>]18)
  • At the start of the screening phase, participant must meet the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnostic criteria for single-episode major depressive disorder (MDD) (if single-episode MDD, the duration must be greater than or equal to [>=] 2 years) or recurrent MDD, without psychotic features, based upon clinical assessment and confirmed by the Mini-International Neuropsychiatric Interview (MINI)
  • At screening, participant must have a MADRS total score of >=22
  • At the start of the screening phase, participants must have had nonresponse to >=2 oral antidepressant treatments in the current episode of depression, as assessed using the the MGHATRQ and confirmed by documented records (example medical/pharmacy/prescription records or a letter from treating a physician, etc,) B). For Transferred-entry Participants
  • All participants who completed the double-blind induction phase of ESKETINTRD3005 study, regardless of their response status, will be eligible to participate in this study, if they meet the study specific eligibility criteria

Exclusion Criteria:

A). For Direct-Entry Participants

  • Participant's depressive symptoms have previously not responded to: Esketamine or ketamine in the current major depressive episode per clinical judgment or All of the 4 oral antidepressant treatment options available in the respective country for the open-label induction phase (that is, duloxetine, escitalopram, sertraline, and venlafaxine XR) in the current major depressive episode (based on Massachusetts General Hospital - Antidepressant Treatment Response Questionnaire [ MGH-ATRQ])
  • Participant has a current or prior DSM-5 diagnosis of a psychotic disorder or MDD with psychotic features, bipolar or related disorders (confirmed by the MINI), obsessive compulsive disorder (current only), intellectual disability (DSM-5 diagnostic codes 317, 318.0, 318.1, 318.2, 315.8, and 319), autism spectrum disorder, borderline personality disorder, antisocial personality disorder, histrionic personality disorder, or narcissistic personality disorder
  • Participant has homicidal ideation/intent, per the investigator's clinical judgment, or has suicidal ideation with some intent to act within 6 months prior to the start of the screening phase, per the investigator's clinical judgment or based on the Columbia Suicide Severity Rating Scale (C-SSRS)
  • Participants with history of moderate or severe substance or alcohol use disorder according to DSM-5 criteria
  • Participants who has a Mini Mental State Examination (MMSE) <25; Has neurodegenerative disorder (example, Alzheimer's disease, vascular dementia, Parkinson's disease), or evidence of mild cognitive impairment (MCI) B). Transferred-Entry Participants
  • Participant has taken any prohibited therapies that would not permit dosing on Day 1
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02497287


Contacts
Contact: Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions: JNJ.CT@sylogent.com

  Show 200 Study Locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

Additional Information:
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT02497287     History of Changes
Other Study ID Numbers: CR107148
ESKETINTRD3004 ( Other Identifier: Janssen Research & Development, LLC )
2014-004587-38 ( EudraCT Number )
First Submitted: May 18, 2015
First Posted: July 14, 2015
Last Update Posted: October 24, 2017
Last Verified: October 2017

Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Janssen Research & Development, LLC:
Treatment-resistant Depression
Esketamine
Oral Antidepressant

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Treatment-Resistant
Behavioral Symptoms
Mood Disorders
Mental Disorders
Antidepressive Agents
Citalopram
Duloxetine Hydrochloride
Sertraline
Venlafaxine Hydrochloride
Dexetimide
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antiparkinson Agents
Anti-Dyskinesia Agents
Parasympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Serotonin and Noradrenaline Reuptake Inhibitors