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A Double-blind Study to Assess the Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicidal Ideation, in Participants Who Are Assessed to be at Imminent Risk for Suicide

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ClinicalTrials.gov Identifier: NCT02133001
Recruitment Status : Completed
First Posted : May 7, 2014
Last Update Posted : October 14, 2016
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Study Description
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Brief Summary:
The purpose of this study is to evaluate the efficacy of intranasal esketamine 84 milligram (mg) compared with intranasal placebo along with standard care treatment, in reducing the symptoms of major depressive disorder (MDD) (an affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities, the mood disturbance is prominent and relatively persistent), including the risk for suicide as assessed by the Investigator, in participants who will be assessed to be at imminent risk for suicide.

Condition or disease Intervention/treatment Phase
Major Depressive Disorder Drug: Esketamine Drug: Placebo Phase 2

Detailed Description:
This is a randomized (study medication assigned to participants by chance), double-blind (neither physician nor participant knows assigned study treatment), placebo-controlled (participants are randomly assigned to a test treatment or to an identical-appearing treatment that does not contain the test drug), and multicenter (when more than one hospital or medical school team works on a medical research study), study of esketamine in participants with major depressive disorder (MDD) in participants who will be assessed to be at imminent risk for suicide, as measured by the change from Baseline on the Montgomery-Asberg Depression Rating Scale (MADRS) total score at 4 hours postdose on Day 1. The duration of study will be approximately 81 days per participant. The study consists of 3 parts: Screening (that is, with in 1 day before study commences on Day 1) and double-blind Treatment (from Day 1-25) and Follow-up (from Day 26 up to Day 81). All the eligible participants will be provided standard care treatment and will be randomly assigned to either esketmaine or placebo treatment. Esketamine/placebo will be administered by intranasal route (delivery of medications through the nasal mucosa) two times per week for 4 weeks. Efficacy of the participants will be primarily evaluated through MADRS. Participants' safety will be monitored throughout the study.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 68 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Double-blind, Randomized, Placebo Controlled Study to Evaluate the Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicidal Ideation, in Subjects Who Are Assessed to be at Imminent Risk for Suicide
Study Start Date : May 2014
Actual Primary Completion Date : February 2016
Actual Study Completion Date : February 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Suicide
U.S. FDA Resources

Arms and Interventions
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Arm Intervention/treatment
Experimental: Esketamine
Esketamine hydrochloride solution (containing 14 milligram (mg) of esketamine base per 100 microliter [mcl] of intranasal spray) will be administered by intranasal route using nasal spray pump as two times a week, for 4 weeks. Dose may be reduced to 56 mg per day based on Investigator's discretion.
 Drug: Esketamine
Esketamine 84 mg will be self-administered by participants as intranasal spray as two times a week, for 4 weeks (that is, Day 1,4,8,11,15,18,22,25). Dose may be reduced to 56 mg per day based on Investigator's discretion.
Other Name: Esketamine hydrochloride
Placebo Comparator: Placebo
Matching Placebo solution will be administered by intranasal route using nasal spray pump as two times a week, for 4 weeks.
 Drug: Placebo
Matching placebo will be self-administered by participants as intranasal spray as two times a week, for 4 weeks (that is, Day 1,4,8,11,15,18,22,25).


Outcome Measures
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Primary Outcome Measures :
  1. Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Hour 4 Post-administration of Study Treatment on Day 1 [ Time Frame: Baseline and 4 hours post-administration of study treatment on Day 1 ]
    The MADRS measures the overall severity of depressive symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).


Secondary Outcome Measures :
  1. Change From Baseline in Clinician's Assessment of Suicide Risk Based on Suicide Ideation and Behavior Assessment Tool (SIBAT) at Hour 4 post-administration of Study Treatment on Day 1 [ Time Frame: Baseline and 4 hours post-administration of study treatment on Day 1 ]
    Clinician's assessment of suicide risk will be assessed by SIBAT. The SIBAT clinical global judgment of suicide risk is derived from the Clinical Global Impression Severity of Suicidality (CGI-SS) of the Intersept Scale for Suicidal Thinking (ISST). The clinical global judgment of suicide risk summarizes clinician overall judgment of suicide risk based on information gathered from the full instrument. The SIBAT will serve as both an efficacy and safety parameter.

  2. Change From Baseline in Beck Scale for Suicidal Ideation (BSS) Total Score at Hour 4 post-administration of Study Treatment on Day 1 [ Time Frame: Baseline and 4 hours post-administration of study treatment on Day 1 ]
    The BSS is a participant-rated version of Beck's original, clinician-rated Scale for Suicidal Ideation (SSI). The BSS is a 19-item, participant-completed questionnaire to assess characteristics of depression. Each of the 19 items corresponding to a symptom of depression is summed to give a single score. There is a 3-point scale for each item ranging from 0 to 2 (0 = not present; 2 = present in the extreme). The total score ranges from 0 to 38 with higher the score indicating more severe depressive symptoms.

  3. Percentage of Participants with Response Based on Montgomery-Asberg Depression Rating Scale (MADRS) Total Score [ Time Frame: Day 1 up to Day 25 ]
    Response is defined as a greater than or equal to 50 percent reduction from Baseline in the MADRS total score from Day 1 through Day 25. The MADRS measures the overall severity of depressive symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).

  4. Change From Baseline in Depressive Symptoms Based on MADRS Total Score at Day 25 [ Time Frame: Day 1 and Day 25 ]
    The MADRS measures the overall severity of depressive symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).

  5. Change From Baseline in Clinician's Assessment of Suicide Risk Based on Suicide Ideation and Behavior Assessment Tool (SIBAT) at Day 25 and Day 81 [ Time Frame: Day 1, Day 25 and Day 81 ]
    Clinician's assessment of suicide risk will be assessed by SIBAT. The SIBAT clinical global judgment of suicide risk is derived from the Clinical Global Impression Severity of Suicidality (CGI-SS) of the Intersept Scale for Suicidal Thinking (ISST). The clinical global judgment of suicide risk summarizes clinician overall judgment of suicide risk based on information gathered from the full instrument. The SIBAT will serve as both an efficacy and safety parameter.

  6. Change From Baseline in Beck Scale for Suicidal Ideation (BSS) Total Score at Day 25 and Day 81 [ Time Frame: Day 1, Day 25 and Day 81 ]
    The BSS is a participant-rated version of Beck's original, clinician-rated Scale for Suicidal Ideation (SSI). The BSS is a 19-item, participant-completed questionnaire to assess characteristics of depression. Each of the 19 items corresponding to a symptom of depression is summed to give a single score. There is a 3-point scale for each item ranging from 0 to 2 (0 = not present; 2 = present in the extreme). The total score ranges from 0 to 38 with higher the score indicating more severe depressive symptoms.

  7. Change From Baseline in Beck Hopelessness Scale (BHS) Score at Day 25 [ Time Frame: Day 1 and Day 25 ]
    The BHS measures the extent of negative attitudes about the future. It has particular utility as an indirect indicator of suicidal risk in depressed examinees or individuals who have made suicide attempts. It consists of 20 true-false items that examine the respondent's attitude over the past week by either endorsing a pessimistic statement or denying an optimistic statement; 9 are keyed false and 11 are keyed true. These items fall within 3 domains: (1) feelings about the future; (2) loss of motivation; and (3) future expectations. For every statement, each response is assigned a score of 0 or 1. The total BHS score is a sum of item responses and can range from 0 to 20, with a higher score representing a higher level of hopelessness. Total scores that range from 0 to 3 are considered within the normal range, scores 4 to 8 identify mild hopelessness, scores 9 to 14 identify moderate hopelessness, and scores greater than 14 identify severe hopelessness.

  8. Change From Baseline in Participant's Assessment of Suicide Risk at Day 25 [ Time Frame: Day 1 and Day 25 ]
    Participant's assessment of suicide risk will be assessed by Suicide Ideation and Behavior Assessment Tool (SIBAT). The participant global judgment of suicide risk summarizes participant's overall judgment of suicide risk based on information gathered from the full instrument. SIBAT will serve as both an efficacy and safety parameter.


Eligibility Criteria
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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:

  • Participants must meet Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) diagnostic criteria for major depressive disorder
  • Participants must have current suicidal ideation with intent
  • In the Investigator's opinion, participant must be in need of acute psychiatric hospitalization due to imminent risk of suicide
  • Participant has a Montgomery Asberg Depression Rating Scale (MADRS) total score of greater than or equal to (>=) 22 predose on Day 1
  • As part of standard of care treatment, participant agrees to be hospitalized voluntarily for a recommended period of 5 days after randomization (that is, through Day 5), and take prescribed non-investigational antidepressant therapy(ies) for at least the duration of the double-blind treatment phase (Day 25)

Exclusion Criteria:

  • Participant has a current clinical diagnosis of bipolar or related disorders, intellectual disability, or cluster b personality disorder (example, borderline personality disorder, antisocial personality disorder, histrionic personality disorder, and narcissistic personality disorder)
  • Participant meets DSM-IV criteria for borderline personality disorder, based on clinical interview
  • Participant has a current or prior diagnosis of a psychotic disorder, major depressive disorder (MDD) with psychosis, or obsessive compulsive disorder
  • Participant with a history or current signs and symptoms of liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, or metabolic disturbances
  • Participant has uncontrolled hypertension (systolic blood pressure greater than [>] 160 millimeter of mercury [mmHg] or diastolic blood pressure > 90 mmHg) despite diet, exercise or a stable dose of an allowed anti-hypertensive treatment at Screening; or any past history of hypertensive crisis
Contacts and Locations
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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): NCT02133001


Locations
United States, Alabama
Birmingham, Alabama, United States
United States, California
San Diego, California, United States
United States, Connecticut
Hartford, Connecticut, United States
New Haven, Connecticut, United States
United States, Georgia
Atlanta, Georgia, United States
United States, Iowa
Iowa City, Iowa, United States
United States, Maryland
Baltimore, Maryland, United States
Towson, Maryland, United States
United States, Michigan
Ann Arbor, Michigan, United States
United States, Minnesota
Rochester, Minnesota, United States
United States, Ohio
Cincinnati, Ohio, United States
United States, Pennsylvania
Philadelphia, Pennsylvania, United States
Pittsburgh, Pennsylvania, United States
United States, Texas
Houston, Texas, United States
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
More Information
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT02133001     History of Changes
Other Study ID Numbers: CR103162
ESKETINSUI2001 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: May 7, 2014    Key Record Dates
Last Update Posted: October 14, 2016
Last Verified: October 2016

Keywords provided by Janssen Research & Development, LLC:
Major Depressive Disorder
Esketamine
Intranasal esketamine
Placebo

Additional relevant MeSH terms:
Disease
Depressive Disorder
Depression
Depressive Disorder, Major
Suicide
Suicidal Ideation
 Pathologic Processes
Mood Disorders
Mental Disorders
Behavioral Symptoms
Self-Injurious Behavior