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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01640080
First received: July 11, 2012
Last updated: July 9, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Major Depressive Disorder
Drug: Esketamine
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Double-Blind, Double-Randomization, Placebo-Controlled Study of the Efficacy of Intravenous Esketamine in Adult Subjects With Treatment-Resistant Depression

Resource links provided by NLM:


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

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 [ Time Frame: Day 1 (baseline), Day 2 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 (baseline), Day 4 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 (baseline), Day 35 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 (baseline), Day 2 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Day 1 (baseline), Day 4 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Day 1 (baseline), Day 14 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 (baseline), Day 7 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Day 1 (baseline), Day 7 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 (baseline), Day 7 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Day 1 (baseline), Day 7 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 4, Day 7 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 (baseline), Day 3 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 (baseline), Day 4 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Day 4, Day 7 ] [ Designated as safety issue: No ]
    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.


Enrollment: 30
Study Start Date: June 2012
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Esketamine (Group 1) Drug: Esketamine
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.
Experimental: Esketamine (Group 2) Drug: Esketamine
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.
Placebo Comparator: Placebo Drug: Placebo
Form= intravenous infusion, route= intravenous use. One single placebo intravenous infusion administered on Day 1 and Day 4.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01640080

Locations
Belgium
Dave, Belgium
Gent, Belgium
Kortenberg, Belgium
Lede, Belgium
Germany
Berlin, Germany
Freiburg, Germany
Mainz, Germany
Munchen, Germany
Poland
Gdansk, Poland
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01640080     History of Changes
Other Study ID Numbers: CR100843, ESKETIVTRD2001, 2011-005992-17
Study First Received: July 11, 2012
Last Updated: July 9, 2013
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Germany: Federal Institute for Drugs and Medical Devices
Germany: Ethics Commission

Keywords provided by Janssen Research & Development, LLC:
Major depressive disorder
Treatment resistant depression
Depression
Esketamine

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Mental Disorders

ClinicalTrials.gov processed this record on April 14, 2014