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A Study of the Efficacy of Intravenous Esketamine in Adult Patients With Treatment-Resistant Depression

Primary Purpose

Major Depressive Disorder

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Esketamine
Esketamine
Placebo
Sponsored by
Janssen Research & Development, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Major Depressive Disorder focused on measuring Major depressive disorder, Treatment resistant depression, Depression, Esketamine

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Be medically stable on the basis of clinical laboratory tests
  • Diagnostic for major depressive disorder (MDD) without psychotic features
  • Have an inadequate response to at least 1 antidepressant in the current episode of depression and at least one other inadequate treatment response to an antidepressant either in the current episode or in a previous episode
  • Women must be not pregnant; women must be postmenopausal, surgically sterile or, if heterosexually active, practicing a highly effective method of birth control during the study and for 3 months after receiving the last dose of study drug
  • Men must agree to use a double barrier method of birth control and to not donate sperm during the study and for 3 months after receiving the last dose of study drug
  • Signed informed consent document

Exclusion Criteria:

  • History of, or current signs and symptoms of diseases or conditions that would make participation not be in the best interest (eg, compromise the well-being) of the patient or that could prevent, limit, or confound the protocol-specified assessments
  • Has uncontrolled hypertension (systolic blood pressure (SBP)> 160 mmHg or diastolic blood pressure (DBP)> 90 mmHg despite diet, exercise or a stable dose of an allowed anti-hypertensive treatment) or any past history of hypertensive crisis
  • Has known human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection, or have positive results at screening
  • Has a primary diagnosis of current (active) generalized anxiety disorder, panic disorder, obsessive compulsive disorder, posttraumatic stress disorder, anorexia nervosa, or bulimia nervosa
  • Has a history or current diagnosis of a psychotic disorder, bipolar disorder, mental retardation, or borderline personality disorders, mood disorder with postpartum onset, somatoform disorders or chronic fatigue syndrome
  • Has had major surgery, (eg, requiring general or local anesthesia) within 4 weeks before screening, or will not have fully recovered from surgery, or planned surgery during the time the subject is expected to participate in the study

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

Esketamine (Group 1)

Esketamine (Group 2)

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Change from Day 1 (baseline) to Day 2 in the Montgomery Asberg Depression Rating Scale (MADRS) total score in the double-blind treatment phase
The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total score of 60. Higher scores represent a more severe condition.

Secondary Outcome Measures

Change from Day 1 (baseline) to Day 4 in Major Depressive Disorder (MDD) symptoms using the Montgomery Asberg Depression Rating Scale (MADRS) total score in the double-blind treatment phase
The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total score of 60. Higher scores represent a more severe condition.
Change from Day 1 (baseline) to Day 35 in Major Depressive Disorder (MDD) symptoms using the Montgomery Asberg Depression Rating Scale (MADRS) total score during the posttreatment phase
The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total score of 60. Higher scores represent a more severe condition.
The number of patients who have a reduction in Montgomery Asberg Depression Rating Scale (MADRS) total score of >50% versus baseline on Day 2
The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total score of 60. Higher scores represent a more severe condition.
Change from Day 1 (baseline) to Day 4 in Major Depressive Disorder (MDD) symptoms using the Quick Inventory of Depressive Symptomatology-Self Report- 14-Item (QIDS-SR14)
The QIDS-SR14, s a version of the QIDS-SR16 with a shorter, 24-hour recall period that has been developed for this trial. The total score ranges from 0 to 27. Using a scale of severity of depression of none, mild, moderate, severe, and very severe, corresponding QIDS-SR16 total scores are none 1-5, mild 6-10, moderate 11-15, severe 16-20 and very severe 21-27.
Change from Day 1 (baseline) to Day 14 in Major Depressive Disorder (MDD) symptoms using the Quick Inventory of Depressive Symptomatology-Self Report-16-item (QIDS-SR16)
The QIDS-SR16 is a patient reported measure designed to assess the severity of depressive symptoms. The total score ranges from 0 to 27. Using a scale of severity of depression of none, mild, moderate, severe, and very severe, corresponding QIDS-SR16 total scores are none 1-5, mild 6-10, moderate 11-15, severe 16-20 and very severe 21-27.
Change from Day 1 (baseline) to Day 7 in severity of illness using the Clinical Global Impression- Severity (CGI-S) for esketamine compared to placebo
The CGI-S is a physician-rated scale that is designed to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis and improvement with treatment. Considering total clinical experience, a patient is assessed on severity of mental illness at the time of rating 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 the most extremely ill patients.
Change from Day 1 (baseline) to Day 7 of global change in Major Depressive Disorder (MDD) since start of study treatment, as measured by the Clinical Global Impression- Improvement (CGI-I)
The CGI-I is a 7-point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention and rated as: 0= not assessed; 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse.
Change from Day 1 (baseline) to Day 7 in severity of illness using the Patient Global Impression - Severity (PGI-S) for esketamine compared to placebo
The PGI-S is a 4-point scale that requires the patient to rate the severity of their illness at the time of assessment, relative to the patient's past experience. Considering their total experience, the patient assesses the severity of their depression illness at the time of rating as none, mild, moderate or severe.
Change from Day 1 (baseline) to Day 7 in patient perspective of global change in Major Depressive Disorder (MDD) since start of study treatment, as measured by the Patient Global Impression of Change (PGI-C)
The PGI-C is a 7-point scale that requires the patient to assess how much their illness has improved or worsened relative to a baseline state at the beginning of the intervention. The response options are: very much improved; much improved; improved (just enough to make a difference); no change; worse (just enough to make a difference); much worse; or very much worse.
Change from Day 4 to Day 7 in Major Depressive Disorder (MDD) symptoms using the Montgomery Asberg Depression Rating Scale (MADRS) total score in the double-blind treatment phase
The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total score of 60. Higher scores represent a more severe condition.
The number of patients who have a reduction in Montgomery Asberg Depression Rating Scale (MADRS) total score of >50% versus baseline on Day 3
The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total score of 60. Higher scores represent a more severe condition.
The number of patients who have a reduction in Montgomery Asberg Depression Rating Scale (MADRS) total score of >50% versus baseline on Day 4
The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total score of 60. Higher scores represent a more severe condition.
Change from Day 4 to Day 7 in Major Depressive Disorder (MDD) symptoms using the Quick Inventory of Depressive Symptomatology-Self Report- 14-Item (QIDS-SR14)
The QIDS-SR14, s a version of the QIDS-SR16 with a shorter, 24-hour recall period that has been developed for this trial. The total score ranges from 0 to 27. Using a scale of severity of depression of none, mild, moderate, severe, and very severe, corresponding QIDS-SR16 total scores are none 1-5, mild 6-10, moderate 11-15, severe 16-20 and very severe 21-27.

Full Information

First Posted
July 11, 2012
Last Updated
May 29, 2020
Sponsor
Janssen Research & Development, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT01640080
Brief Title
A Study of the Efficacy of Intravenous Esketamine in Adult Patients With Treatment-Resistant Depression
Official Title
A Double-Blind, Double-Randomization, Placebo-Controlled Study of the Efficacy of Intravenous Esketamine in Adult Subjects With Treatment-Resistant Depression
Study Type
Interventional

2. Study Status

Record Verification Date
May 2020
Overall Recruitment Status
Completed
Study Start Date
June 27, 2012 (Actual)
Primary Completion Date
June 3, 2013 (Actual)
Study Completion Date
June 3, 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC

4. Oversight

5. Study Description

Brief Summary
The purpose of this study is to assess the efficacy of esketamine compared with placebo in improving symptoms of depression in patients with treatment resistant depression.
Detailed Description
This is a double-blind (neither physician nor patient knows the treatment that the patient receives), double-randomization (the study drug is assigned by chance), placebo-controlled (placebo is an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial), multiple dose titration study in adult patients with treatment resistant depression (TRD). The study will assess the efficacy of esketamine at 24 hours after dosing on Day 1, administered as a 0.40 mg/kg and 0.20 mg/kg intravenous (i.v.) infusion, compared with placebo in improving symptoms of depression in patients with TRD, using the Montgomery-Asberg Depression Rating Scale (MADRS). The study will consist of 3 phases: a screening phase of up to 2 weeks, a 7-day double-blind treatment phase (Day 1 to Day 7), and a 4-week posttreatment (follow up) phase. The interval between the first and last dose of study medication is 3 days. The total study duration for each patient will be a maximum of 7 weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depressive Disorder
Keywords
Major depressive disorder, Treatment resistant depression, Depression, Esketamine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Esketamine (Group 1)
Arm Type
Experimental
Arm Title
Esketamine (Group 2)
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Esketamine
Intervention Description
Type= exact number, number= 0.20, unit= mg/kg, form= intravenous infusion, route= intravenous use. One single intravenous infusion of esketamine 0.20 mg/kg administered on Day 1 and Day 4.
Intervention Type
Drug
Intervention Name(s)
Esketamine
Intervention Description
Type= exact number, number= 0.40, unit= mg/kg, form= intravenous infusion, route= intravenous use. One single intravenous infusion of esketamine 0.40 mg/kg administered on Day 1 and Day 4.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Form= intravenous infusion, route= intravenous use. One single placebo intravenous infusion administered on Day 1 and Day 4.
Primary Outcome Measure Information:
Title
Change from Day 1 (baseline) to Day 2 in the Montgomery Asberg Depression Rating Scale (MADRS) total score in the double-blind treatment phase
Description
The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total score of 60. Higher scores represent a more severe condition.
Time Frame
Day 1 (baseline), Day 2
Secondary Outcome Measure Information:
Title
Change from Day 1 (baseline) to Day 4 in Major Depressive Disorder (MDD) symptoms using the Montgomery Asberg Depression Rating Scale (MADRS) total score in the double-blind treatment phase
Description
The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total score of 60. Higher scores represent a more severe condition.
Time Frame
Day 1 (baseline), Day 4
Title
Change from Day 1 (baseline) to Day 35 in Major Depressive Disorder (MDD) symptoms using the Montgomery Asberg Depression Rating Scale (MADRS) total score during the posttreatment phase
Description
The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total score of 60. Higher scores represent a more severe condition.
Time Frame
Day 1 (baseline), Day 35
Title
The number of patients who have a reduction in Montgomery Asberg Depression Rating Scale (MADRS) total score of >50% versus baseline on Day 2
Description
The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total score of 60. Higher scores represent a more severe condition.
Time Frame
Day 1 (baseline), Day 2
Title
Change from Day 1 (baseline) to Day 4 in Major Depressive Disorder (MDD) symptoms using the Quick Inventory of Depressive Symptomatology-Self Report- 14-Item (QIDS-SR14)
Description
The QIDS-SR14, s a version of the QIDS-SR16 with a shorter, 24-hour recall period that has been developed for this trial. The total score ranges from 0 to 27. Using a scale of severity of depression of none, mild, moderate, severe, and very severe, corresponding QIDS-SR16 total scores are none 1-5, mild 6-10, moderate 11-15, severe 16-20 and very severe 21-27.
Time Frame
Day 1 (baseline), Day 4
Title
Change from Day 1 (baseline) to Day 14 in Major Depressive Disorder (MDD) symptoms using the Quick Inventory of Depressive Symptomatology-Self Report-16-item (QIDS-SR16)
Description
The QIDS-SR16 is a patient reported measure designed to assess the severity of depressive symptoms. The total score ranges from 0 to 27. Using a scale of severity of depression of none, mild, moderate, severe, and very severe, corresponding QIDS-SR16 total scores are none 1-5, mild 6-10, moderate 11-15, severe 16-20 and very severe 21-27.
Time Frame
Day 1 (baseline), Day 14
Title
Change from Day 1 (baseline) to Day 7 in severity of illness using the Clinical Global Impression- Severity (CGI-S) for esketamine compared to placebo
Description
The CGI-S is a physician-rated scale that is designed to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis and improvement with treatment. Considering total clinical experience, a patient is assessed on severity of mental illness at the time of rating 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 the most extremely ill patients.
Time Frame
Day 1 (baseline), Day 7
Title
Change from Day 1 (baseline) to Day 7 of global change in Major Depressive Disorder (MDD) since start of study treatment, as measured by the Clinical Global Impression- Improvement (CGI-I)
Description
The CGI-I is a 7-point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention and rated as: 0= not assessed; 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse.
Time Frame
Day 1 (baseline), Day 7
Title
Change from Day 1 (baseline) to Day 7 in severity of illness using the Patient Global Impression - Severity (PGI-S) for esketamine compared to placebo
Description
The PGI-S is a 4-point scale that requires the patient to rate the severity of their illness at the time of assessment, relative to the patient's past experience. Considering their total experience, the patient assesses the severity of their depression illness at the time of rating as none, mild, moderate or severe.
Time Frame
Day 1 (baseline), Day 7
Title
Change from Day 1 (baseline) to Day 7 in patient perspective of global change in Major Depressive Disorder (MDD) since start of study treatment, as measured by the Patient Global Impression of Change (PGI-C)
Description
The PGI-C is a 7-point scale that requires the patient to assess how much their illness has improved or worsened relative to a baseline state at the beginning of the intervention. The response options are: very much improved; much improved; improved (just enough to make a difference); no change; worse (just enough to make a difference); much worse; or very much worse.
Time Frame
Day 1 (baseline), Day 7
Title
Change from Day 4 to Day 7 in Major Depressive Disorder (MDD) symptoms using the Montgomery Asberg Depression Rating Scale (MADRS) total score in the double-blind treatment phase
Description
The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total score of 60. Higher scores represent a more severe condition.
Time Frame
Day 4, Day 7
Title
The number of patients who have a reduction in Montgomery Asberg Depression Rating Scale (MADRS) total score of >50% versus baseline on Day 3
Description
The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total score of 60. Higher scores represent a more severe condition.
Time Frame
Day 1 (baseline), Day 3
Title
The number of patients who have a reduction in Montgomery Asberg Depression Rating Scale (MADRS) total score of >50% versus baseline on Day 4
Description
The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total score of 60. Higher scores represent a more severe condition.
Time Frame
Day 1 (baseline), Day 4
Title
Change from Day 4 to Day 7 in Major Depressive Disorder (MDD) symptoms using the Quick Inventory of Depressive Symptomatology-Self Report- 14-Item (QIDS-SR14)
Description
The QIDS-SR14, s a version of the QIDS-SR16 with a shorter, 24-hour recall period that has been developed for this trial. The total score ranges from 0 to 27. Using a scale of severity of depression of none, mild, moderate, severe, and very severe, corresponding QIDS-SR16 total scores are none 1-5, mild 6-10, moderate 11-15, severe 16-20 and very severe 21-27.
Time Frame
Day 4, Day 7

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Be medically stable on the basis of clinical laboratory tests Diagnostic for major depressive disorder (MDD) without psychotic features Have an inadequate response to at least 1 antidepressant in the current episode of depression and at least one other inadequate treatment response to an antidepressant either in the current episode or in a previous episode Women must be not pregnant; women must be postmenopausal, surgically sterile or, if heterosexually active, practicing a highly effective method of birth control during the study and for 3 months after receiving the last dose of study drug Men must agree to use a double barrier method of birth control and to not donate sperm during the study and for 3 months after receiving the last dose of study drug Signed informed consent document Exclusion Criteria: History of, or current signs and symptoms of diseases or conditions that would make participation not be in the best interest (eg, compromise the well-being) of the patient or that could prevent, limit, or confound the protocol-specified assessments Has uncontrolled hypertension (systolic blood pressure (SBP)> 160 mmHg or diastolic blood pressure (DBP)> 90 mmHg despite diet, exercise or a stable dose of an allowed anti-hypertensive treatment) or any past history of hypertensive crisis Has known human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection, or have positive results at screening Has a primary diagnosis of current (active) generalized anxiety disorder, panic disorder, obsessive compulsive disorder, posttraumatic stress disorder, anorexia nervosa, or bulimia nervosa Has a history or current diagnosis of a psychotic disorder, bipolar disorder, mental retardation, or borderline personality disorders, mood disorder with postpartum onset, somatoform disorders or chronic fatigue syndrome Has had major surgery, (eg, requiring general or local anesthesia) within 4 weeks before screening, or will not have fully recovered from surgery, or planned surgery during the time the subject is expected to participate in the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
City
Dave
Country
Belgium
City
Gent
Country
Belgium
City
Kortenberg
Country
Belgium
City
Lede
Country
Belgium
City
Berlin
Country
Germany
City
Freiburg
Country
Germany
City
Mainz
Country
Germany
City
Munchen
Country
Germany
City
Gdansk
Country
Poland

12. IPD Sharing Statement

Citations:
PubMed Identifier
31270774
Citation
Lewis S, Romano C, De Bruecker G, Murrough JW, Shelton R, Singh JB, Jamieson C. Analysis of Clinical Trial Exit Interview Data in Patients with Treatment-Resistant Depression. Patient. 2019 Oct;12(5):527-537. doi: 10.1007/s40271-019-00369-8.
Results Reference
derived
PubMed Identifier
28086004
Citation
Johnson KM, Devine JM, Ho KF, Howard KA, Saretsky TL, Jamieson CA. Evidence to Support Montgomery-Asberg Depression Rating Scale Administration Every 24 Hours to Assess Rapid Onset of Treatment Response. J Clin Psychiatry. 2016 Dec;77(12):1681-1686. doi: 10.4088/JCP.15m10253.
Results Reference
derived
PubMed Identifier
26707087
Citation
Singh JB, Fedgchin M, Daly E, Xi L, Melman C, De Bruecker G, Tadic A, Sienaert P, Wiegand F, Manji H, Drevets WC, Van Nueten L. Intravenous Esketamine in Adult Treatment-Resistant Depression: A Double-Blind, Double-Randomization, Placebo-Controlled Study. Biol Psychiatry. 2016 Sep 15;80(6):424-431. doi: 10.1016/j.biopsych.2015.10.018. Epub 2015 Nov 3.
Results Reference
derived

Learn more about this trial

A Study of the Efficacy of Intravenous Esketamine in Adult Patients With Treatment-Resistant Depression

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