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A Study to Evaluate the Efficacy, Safety, and Tolerability of Fixed Doses of Intranasal Esketamine Plus an Oral Antidepressant in Adult Participants With Treatment-resistant Depression (TRANSFORM-1)

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. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02417064
Recruitment Status : Completed
First Posted : April 15, 2015
Results First Posted : April 18, 2019
Last Update Posted : April 18, 2019
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Brief Summary:
The purpose of this study is to compare the efficacy and safety of switching treatment-resistant depression (TRD) participants 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.

Condition or disease Intervention/treatment Phase
Treatment-resistant Depression Drug: Esketamine Drug: Placebo Drug: Duloxetine (Oral Antidepressant) Drug: Escitalopram (Oral antidepressant) Drug: Sertraline (Oral Antidepressant) Drug: Venlafaxine Extended Release (XR) (Oral Antidepressant) Phase 3

Detailed Description:
This is a randomized, double-blind (neither the researchers nor the participants know what treatment the participant is receiving), active-controlled, multicenter study (more than 1 study site) in participants with TRD to assess the efficacy, safety, and tolerability of fixed 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). Participants who rollover into a long-term maintenance study will not participate in the Follow-up Phase. At the start of the screening/prospective observational phase, the participant must have had documented non-response to at least 1 antidepressant treatment (based on Massachusetts General Hospital - Antidepressant Treatment Response Questionnair [MGH-ATRQ]) in the current episode of depression, and participant is taking a different oral antidepressant treatment on the MGH-ATRQ for at least the previous 2 weeks at or above the minimum therapeutic dose. This antidepressant treatment, as well as any other ongoing medications being taken for depression at screening (including adjunctive/ augmentation therapies), will continue from the start of Week 1 through the end of Week 4 of the screening/prospective observational phase. Participants will be randomly assigned to receive Intranasal esketamine (56 milligrams [mg]), Intranasal esketamine (84 mg), or Intranasal placebo. In addition, each participant will be assigned to receive 1 of 4 oral antidepressant medications from 2 different classes of antidepressant treatments, a Selective Serotonin Reuptake Inhibitor (SSRI) (escitalopram or sertraline) or a Serotonin and Norepinephrine Reuptake Inhibitor (SNRI) (duloxetine or venlafaxine extended release [XR]), initiated on Day 1 and continued through the double-blind induction phase. Participants will be primarily evaluated for improvement in depressive symptoms as assessed by change in Montgomery-Asberg Depression Rating Scale (MADRS) total score at Week 4. Participants' safety will be monitored throughout the study.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 346 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Multicenter, Active-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Fixed Doses of Intranasal Esketamine Plus an Oral Antidepressant in Adult Subjects With Treatment-resistant Depression
Actual Study Start Date : August 10, 2015
Actual Primary Completion Date : February 20, 2018
Actual Study Completion Date : February 20, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Antidepressants

Arm Intervention/treatment
Experimental: Intranasal Esketamine 84mg plus Oral Antidepressant
As part of an initial titration, participants will self-administer 56 milligrams (mg) of esketamine intranasally on Day 1, and then 84 mg from Day 4 onwards, twice per week for 4 weeks as a fixed dose regimen in Double-Blind Induction Phase. In addition participants will simultaneously initiate a new, open-label oral antidepressant (i.e, duloxetine, escitalopram, sertraline, or venlafaxine extended release [XR]) on Day 1 that will be continued for the duration of Double-Blind Induction Phase.
Drug: Esketamine
Participants will self-administer either 84 mg or 56 mg of esketamine, intranasally, twice per week for 4 weeks as a fixed dose regimen in Double-Blind Induction Phase.

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. Escitalopram will be titrated up to a dose of 20 mg/day, but if not tolerated the dose can be reduced to the minimum therapeutic dose of 10 mg/day.

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 200 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 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.

Experimental: Esketamine 56 mg plus Oral Antidepressant
Starting from Day 1, participants will self-administer 56 mg of esketamine, intranasally, twice per week for 4 weeks as a fixed dose regimen in Double-Blind Induction Phase. In addition participants will simultaneously initiate a new, open-label oral antidepressant (i.e, duloxetine, escitalopram, sertraline, or venlafaxine XR) on Day 1 that will be continued for the duration of Double-Blind Induction Phase.
Drug: Esketamine
Participants will self-administer either 84 mg or 56 mg of esketamine, intranasally, twice per week for 4 weeks as a fixed dose regimen in Double-Blind Induction Phase.

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. Escitalopram will be titrated up to a dose of 20 mg/day, but if not tolerated the dose can be reduced to the minimum therapeutic dose of 10 mg/day.

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 200 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 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.

Active Comparator: Placebo plus Oral Antidepressant
Participants will self-administer matching placebo, intranasally, twice per week for 4 weeks as a fixed dose regimen in Double-Blind Induction Phase. In addition participants will simultaneously initiate a new, open-label oral antidepressant (i.e, duloxetine, escitalopram, sertraline, or venlafaxine XR) on Day 1 that will be continued for the duration of Double-Blind Induction Phase.
Drug: Placebo
Participants will self-administer matching placebo, intranasally, twice per week for 4 weeks as a fixed dose regimen in Double-Blind Induction Phase.

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. Escitalopram will be titrated up to a dose of 20 mg/day, but if not tolerated the dose can be reduced to the minimum therapeutic dose of 10 mg/day.

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 200 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 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.




Primary Outcome Measures :
  1. Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score up to Day 28 of Double- Blind Induction Phase- Mixed- Effects Model Using Repeated Measures (MMRM) Analysis [ Time Frame: Baseline up to Day 28 of Double-blind Induction Phase ]
    MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition.

  2. Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score up to Endpoint (Double-blind Induction Phase [Day 28])- ANCOVA Analysis [ Time Frame: Baseline up to Double-blind Endpoint (Day 28) ]
    MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition. Missing data was imputed using Last Observation Carried Forward (LOCF) method and last post baseline observation during double-blind induction phase was carried forward as "End Point" for that phase.


Secondary Outcome Measures :
  1. Percentage of Participants With Onset of Clinical Response by Day 2 and Day 8 [ Time Frame: Day 2 up to Day 28 and Day 8 up to Day 28 ]
    A participant was defined as having a clinical response if there was at least 50% improvement (decrease) from baseline in the MADRS total score with onset by Day 2 and Day 8 that was maintained to Day 28. Participants were allowed one excursion (non-response) on Days 8, 15 or 22, however score must show at least 25% improvement. Participants who did not meet these criteria or discontinued during the study before Day 28 were considered as non-responders and were assigned the value of 0 (that is no). MADRS is clinician-rated scale that consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), for total possible score of 0 to 60. Higher scores represent more severe condition.

  2. Change From Baseline in Sheehan Disability Scale (SDS) Total Score up to Day 28 of Double-blind Induction Phase- MMRM Analysis [ Time Frame: Baseline up to Day 28 of Double-blind Induction phase ]
    The SDS is a participant-reported outcome measure and 5 item questionnaire used for assessment of functional impairment and associated disability. The first 3 items assess disruption of 1) work/school, 2) social life, and 3) family life/home responsibilities using 0 (not at all) to 10 (extremely) rating scale. Score for first 3 items are summed to create total score of 0 (unimpaired) to 30 (highly impaired), where higher score indicates greater impairment.

  3. Change From Baseline in Sheehan Disability Scale (SDS) Total Score up to Endpoint (Double-blind Induction Phase [Day 28])- ANCOVA Analysis [ Time Frame: Baseline up to Double-blind Endpoint (Day 28) ]
    The SDS is a participant-reported outcome measure and 5 item questionnaire used for assessment of functional impairment and associated disability. The first 3 items assess disruption of 1) work/school, 2) social life, and 3) family life/home responsibilities using 0 (not at all) to 10 (extremely) rating scale. Score for first 3 items are summed to create total score of 0 (unimpaired) to 30 (highly impaired) where higher score indicates greater impairment. Missing data was imputed using LOCF method and the last post baseline observation during the double-blind induction phase was carried forward as "End Point" for that phase.

  4. Change From Baseline in Patient Health Questionnaire-9 (PHQ-9) Total Score up to Day 28 of Double-blind Induction Phase- MMRM Analysis [ Time Frame: Baseline up to Day 28 of Double-blind Induction phase ]
    PHQ-9 is 9-item, self-reported scale assessing 9 symptom domains of Diagnostic and Statistical Manual of Mental Disorders, Major Depressive Disorder criteria. Each item is rated on 4-point scale (0 = Not at all, 1 = Several Days, 2 = More than half days, 3 = Nearly every day). The scores are summed for a total score ranging from 0-27. Higher score indicates greater severity of depression. Severity of PHQ-9 categorized as follows: None-minimal (0-4), Mild (5-9), Moderate (10-14), Moderately Severe (15-19), Severe (20-27). The recall period is 2 weeks.

  5. Change From Baseline in Patient Health Questionnaire-9 (PHQ-9) Total Score up to Endpoint (Double-blind Induction Phase [Day 28])- ANCOVA Analysis [ Time Frame: Baseline up to Double-blind Endpoint (Day 28) ]
    PHQ-9 is 9-item, self-reported scale assessing 9 symptom domains of Diagnostic and Statistical Manual of Mental Disorders, Major Depressive Disorder criteria. Each item is rated on 4-point scale (0 = Not at all, 1 = Several Days, 2 = More than half days, 3 = Nearly every day). The scores are summed for a total score ranging from 0-27. Higher score indicates greater severity of depression. Severity of PHQ-9 categorized as follows: None-minimal (0-4), Mild (5-9), Moderate (10-14), Moderately Severe (15-19), Severe (20-27). The recall period is 2 weeks. Missing data was imputed using LOCF method and the last post baseline observation during the double-blind induction phase was carried forward as "End Point" for that phase.

  6. Percentage of Participants Who Achieved at Least 50% Reduction From Baseline in MADRS Total Score at Day 28 of Double-blind Induction Phase (Observed Data) [ Time Frame: At Day 28 of Double-blind Induction phase ]
    A participant was defined as a responder (yes=1 and no=0) at a given time point if the percent reduction from baseline in MADRS total score is at least 50 percent (%). The percentage of participants who achieved at least 50% reduction from baseline were reported. MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition.

  7. Percentage of Participants Who Achieved at Least 50% Reduction From Baseline in MADRS Total Score at the Endpoint (Double-blind Induction Phase [Day 28]) (LOCF Data) [ Time Frame: At Day 28 (Double-blind Endpoint) ]
    A participant was defined as a responder (yes=1 and no=0) at a given time point if the percent reduction from baseline in MADRS total score is at least 50 percent (%). The percentage of participants who achieved at least 50% reduction from baseline were reported. MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition. Missing data was imputed using LOCF method and the last post baseline observation during the double-blind induction phase was carried forward as "End Point" for that phase.

  8. Percentage of Participants in Remission (MADRS<=12) at Day 28 of Double-blind Induction Phase (Observed Data) [ Time Frame: At Day 28 of Double-blind Induction Phase ]
    Participants who had a MADRS total score of less than or equal to (<=) 12 were considered as remitters. MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition.

  9. Percentage of Participants in Remission (MADRS<=12) at the Endpoint (Double-blind Induction Phase [Day 28])- ANCOVA Analysis (LOCF Data) [ Time Frame: At Day 28 (Double-blind Endpoint) ]
    Participants who had a MADRS total score of less than or equal to (<=) 12 were considered as remitters. MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition. Missing data was imputed using LOCF method and the last post baseline observation during the double-blind induction phase was carried forward as "End Point" for that phase.

  10. Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score up to Endpoint (Double-blind Induction Phase [Day 28]) [ Time Frame: Baseline up to Double-blind Endpoint (Day 28) ]
    CGI-S provides measure of severity of participant's illness including participant's history, psychosocial circumstances, symptoms, behavior and impact of symptoms on ability to function. CGI-S evaluates severity of psychopathology on scale of 0 to 7. Considering total clinical experience, participant is assessed on severity of mental illness 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 most extremely ill patients (a decrease in score indicates improvement). Missing data was imputed using LOCF method and the last post baseline observation during the double-blind induction phase was carried forward as "End Point" for that phase.

  11. Change From Baseline in Generalized Anxiety Disorder-7 Item (GAD-7) Total Score up to Endpoint (Double-blind Induction Phase [Day 28]) [ Time Frame: Baseline up to Double-blind Endpoint (Day 28) ]
    GAD-7 is a brief and validated 7-item self-reported assessment of overall anxiety. Participants responded to each item using a 4 point scale with response categories of 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 a range of 0 to 21, where higher scores indicate more anxiety. The recall period is 2 weeks. The severity of the GAD-7 is categorized as follows: None (0-4), Mild (5-9), Moderate (10-14) and Severe (15-21). Missing data was imputed using LOCF method and the last post baseline observation during the double-blind induction phase was carried forward as "End Point" for that phase.

  12. Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) up to End of Double-blind Induction Phase (Day 28): Health Status Index [ Time Frame: Baseline up to End of Double-blind Induction Phase (Day 28) ]
    EQ-5D-5L measures health outcome self-completed by respondents. It consists of EQ-5D-5L descriptive system and EQ visual analogue scale (EQ-VAS). The descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each has 5 levels (1-no problem, 2-slight problems, 3-moderate problems, 4-severe problems, 5-extreme problems). The responses are used to generate Health Status Index (HSI). HSI range is -0.148 to 0.949, is anchored at 0 (dead) and 1 (full health).

  13. Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) up to End of Double-blind Induction Phase (Day 28): EQ-VAS [ Time Frame: Baseline up to end of Double-blind induction phase (Day 28) ]
    EQ-5D-5L measures health outcome self-completed by respondents. It consists of EQ-5D-5L descriptive system and EQ visual analogue scale (EQ-VAS). EQ-VAS self-rating records the respondent's own assessment of his/her overall health status at time of completion, on scale of 0 (the worst health you can imagine) to 100 (the best health you can imagine).

  14. Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) up to End of Double-blind Induction Phase (Day 28): Sum Score [ Time Frame: Baseline up to end of Double-blind Induction phase (Day 28) ]
    EQ-5D-5L measures health outcome self-completed by respondents. It consists of EQ-5D-5L descriptive system and EQ visual analogue scale (EQ-VAS). The descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. Each has 5 levels (1-no problem, 2-slight problems, 3-moderate problems, 4-severe problems, 5-extreme problems). The responses are used to generate Health Status Index (HSI). HSI range is -0.148 to 0.949, is anchored at 0 (dead) and 1 (full health). EQ-VAS self-rating records the respondent's own assessment of his/her overall health status at time of completion, on scale of 0 (the worst health you can imagine) to 100 (the best health you can imagine). Sum score ranges from 0 to 100 where, sum score = (sum of the scores from the 5 dimensions minus 5) *5. Higher score indicates worst health state.



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.


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Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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) to 64 years of age, inclusive
  • At the start of the screening/prospective observational 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 the start of the screening/prospective observational phase, participant must have an Inventory of Depressive Symptomatology-Clinician rated ( IDS-C30) total score of greater than or equal to (>=) 34
  • At the start of the screening/prospective observational phase, participants must have had non-response (less than or equal to [<=25] percent [%] improvement) to >=1 but less than or equal to (<=) 5 (if current episode is >2 years, upper limit is applicable to only the last 2 years) oral antidepressant treatments taken at adequate dosage and for adequate duration, as assessed using the Massachusetts General Hospital - Antidepressant Treatment Response Questionnaire (MGH-ATRQ) and documented by medical history and pharmacy/prescription records, for the current episode of depression.

Participant is taking a different oral antidepressant treatment on the MGH-ATRQ for at least the previous 2 weeks at or above the minimum therapeutic dose

- The participant's current major depressive episode, depression symptom severity (Week 1 MADRS total score >=28 required), and antidepressant treatment response in the current depressive episode, must be confirmed using a Site Independent Qualification Assessment

Exclusion Criteria:

  • Participants who have previously demonstrated nonresponse of depressive symptoms to esketamine or ketamine in the current major depressive episode, to all 4 of the oral antidepressant treatment options available for the double-blind induction phase (i.e, duloxetine, escitalopram, sertraline, and venlafaxine extended release [XR]) in the current major depressive episode (based on MGH-ATRQ), or an adequate course of treatment with electroconvulsive therapy (ECT) in the current major depressive episode, defined as at least 7 treatments with unilateral/bilateral ECT
  • Participant has received vagal nerve stimulation (VNS) or has received deep brain stimulation (DBS) in the current episode of depression
  • 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/prospective observational 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

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): NCT02417064


  Show 91 Study Locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  Study Documents (Full-Text)

Documents provided by Janssen Research & Development, LLC:
Study Protocol  [PDF] May 31, 2016
Statistical Analysis Plan  [PDF] November 9, 2017


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Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT02417064     History of Changes
Other Study ID Numbers: CR107146
ESKETINTRD3001 ( Other Identifier: Janssen Research & Development, LLC )
2014-004584-20 ( EudraCT Number )
First Posted: April 15, 2015    Key Record Dates
Results First Posted: April 18, 2019
Last Update Posted: April 18, 2019
Last Verified: March 2019

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

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

Additional relevant MeSH terms:
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Depression
Depressive Disorder
Depressive Disorder, Treatment-Resistant
Behavioral Symptoms
Mood Disorders
Mental Disorders
Antidepressive Agents
Citalopram
Duloxetine Hydrochloride
Sertraline
Venlafaxine Hydrochloride
Esketamine
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