Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

A Study of Ketamine in Patients With Treatment-resistant Depression

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01627782
First received: June 22, 2012
Last updated: June 24, 2016
Last verified: June 2016
  Purpose
The purpose of this study is to explore the optimal dose frequency of ketamine in patients with treatment-resistant depression (TRD).

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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Double-blind, Randomized, Placebo-controlled, Parallel Group, Dose Frequency Study of Ketamine in Subjects With Treatment-resistant Depression

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline to Day 15 [ Time Frame: Baseline (Day 1) and Day 15 ] [ 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 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline to Day 29 [ Time Frame: Baseline (Day 1) and Day 29 ] [ 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.

  • Number of Responders Based on Montgomery-Asberg Depression Rating Scale (MADRS) Total Score [ Time Frame: Day 15 and Day 29 ] [ Designated as safety issue: No ]
    Participants with a reduction in the MADRS total score of greater than or equal to (>=) 50 percent from baseline were defined as responders. 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.

  • Number of Remitters Based on Montgomery-Asberg Depression Rating Scale (MADRS) Total Score [ Time Frame: Day 15 and Day 29 ] [ Designated as safety issue: No ]
    Participants who had a MADRS total score of less than or equal to (<=) 10 were considered remitters. 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.

  • Number of Sustained Responders Based on Montgomery-Asberg Depression Rating Scale (MADRS) Total Score [ Time Frame: Day 15 ] [ Designated as safety issue: No ]
    Sustained response on Day 15 was defined as achieving an onset of antidepressant response within the first week that is maintained to the end of study Day 15. 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 in Clinical Global Impression-Severity (CGI-S) Score From Baseline to Endpoint (Day 29) [ Time Frame: Baseline (Day 1) and Endpoint (Day 29) ] [ Designated as safety issue: No ]
    The CGI-S was used to rate the severity of the participants illness at the time of assessment, relative to the clinician's past experience with participants who had the same diagnosis and improvement with treatment. Considering total clinical experience, a participant was 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 participants.

  • Clinical Global Impression of Improvement (CGI-I) Score at Endpoint of Double Blind Phase [ Time Frame: Endpoint (Day 29) ] [ Designated as safety issue: No ]
    The CGI-I is a 7-point scale that was used to assess how much the participants illness was 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 in Patient Global Impression-Severity (PGI-S) Score From Baseline to Endpoint (Day 29) [ Time Frame: Baseline (Day 1) and Endpoint (Day 29) ] [ Designated as safety issue: No ]
    The PGI-S is an 11-point (0 to 10) scale that required the participant to rate the severity of their illness at the time of assessment, relative to the participants past experience. Considering their total experience, the participant was to assess the severity of their depression illness at the time of rating as none, mild, moderate or severe. The scale is rated as, 0=very well and 10=very poor.

  • Patient Global Impression-Change (PGI-C) Score at Endpoint of Double Blind Phase [ Time Frame: Endpoint (Day 29) ] [ Designated as safety issue: No ]
    The PGI-C is a 7-point scale that required the subject to assess how much their illness had improved or worsened relative to a baseline state at the beginning of the intervention. The response options were: 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. The scale is rated as, 1=very much improved and 7=very much worse.

  • Maximum Observed Plasma Concentration (Cmax) of Ketamine [ Time Frame: Pre-infusion, 20, 40 (End of the Infusion), 45, 50, 60, 90, 120, 180, 240 and 360 minutes post-infusion on Day 1 and Day 15 ] [ Designated as safety issue: No ]
    The Cmax is the maximum observed plasma concentration of drug.

  • Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ketamine [ Time Frame: Pre-infusion, 20, 40 (End of the Infusion), 45, 50, 60, 90, 120, 180, 240 and 360 minutes post-infusion on Day 1 and Day 15 ] [ Designated as safety issue: No ]
    The Tmax is defined as actual sampling time to reach maximum observed drug concentration.

  • Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC[0-last]) [ Time Frame: Pre-infusion, 20, 40 (End of the Infusion), 45, 50, 60, 90, 120, 180, 240 and 360 minutes post-infusion on Day 1 and Day 15 ] [ Designated as safety issue: No ]
    The AUC(0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.

  • Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) [ Time Frame: Pre-infusion, 20, 40 (End of the Infusion), 45, 50, 60, 90, 120, 180, 240 and 360 minutes post-infusion on Day 1 and Day 15 ] [ Designated as safety issue: No ]
    The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC (last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.

  • Total Systemic Clearance (CL) of Ketamine [ Time Frame: Pre-infusion, 20, 40 (End of the Infusion), 45, 50, 60, 90, 120, 180, 240 and 360 minutes post-infusion on Day 1 and Day 15 ] [ Designated as safety issue: No ]
    The CL is a quantitative measure of the rate at which a drug substance is removed from the body.

  • Volume of Distribution at Steady-State (Vss) of Ketamine [ Time Frame: Pre-infusion, 20, 40 (End of the Infusion), 45, 50, 60, 90, 120, 180, 240 and 360 minutes post-infusion on Day 1 and Day 15 ] [ Designated as safety issue: No ]
    The Vss is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of ketamine at steady state.

  • Elimination Half-Life (t1/2) [ Time Frame: Pre-infusion, 20, 40 (End of the Infusion), 45, 50, 60, 90, 120, 180, 240 and 360 minutes post-infusion on Day 1 and Day 15 ] [ Designated as safety issue: No ]
    The elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).


Enrollment: 68
Study Start Date: August 2012
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo 3 times/week Drug: Placebo
Form= intravenous infusion, route= intravenous (IV) use. IV infusions of placebo 2 times weekly or IV infusions of placebo 3 times weekly.
Experimental: Ketamine 3 times/week Drug: Ketamine
Type= exact number, unit= mg/kg, number= 0.5, form= intravenous infusion, route= intravenous (IV) use. IV infusions of ketamine 0.50 mg/kg, 2 times weekly or IV infusions of ketamine 0.50 mg/kg, 3 times weekly.
Experimental: Ketamine 2 times/week Drug: Ketamine
Type= exact number, unit= mg/kg, number= 0.5, form= intravenous infusion, route= intravenous (IV) use. IV infusions of ketamine 0.50 mg/kg, 2 times weekly or IV infusions of ketamine 0.50 mg/kg, 3 times weekly.
Placebo Comparator: Placebo 2 times/week Drug: Placebo
Form= intravenous infusion, route= intravenous (IV) use. IV infusions of placebo 2 times weekly or IV infusions of placebo 3 times weekly.

Detailed Description:
This is a double-blind (patients and study personnel do not know the identity of the administered treatments), randomized (the drug is assigned by chance), placebo-controlled (placebo is a substance that appears identical to the treatment and has no active ingredients), parallel arm study (each group of patients will be treated at the same time). The study will consist of a screening phase of up to 4 weeks, a 4-week double-blind treatment phase (Day 1 to Day 29), and a 3-week post treatment (follow up) phase. In the double-blind phase, patients will receive over 4 weeks either intravenous (IV) infusions of placebo (2 or 3 times weekly) or IV infusions of ketamine (2 or 3 times weekly). The total study duration for each patient will be a maximum of 13 weeks.
  Eligibility

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

Inclusion Criteria:

  • Be medically stable on the basis of clinical laboratory tests performed at screening
  • Meet diagnostic criteria for recurrent major depressive disorder (MDD), without psychotic features
  • Have a history of inadequate response, ie treatment was not successful, to at least 1 antidepressant
  • Have an Inventory of Depressive Symptoms-Clinician rated, 30 item (IDS-C30) total score >= 40 at screening and predose at Day 1
  • Inpatient or agreed to be admitted to the clinic on each dosing day

Exclusion Criteria:

  • Has uncontrolled hypertension
  • Has a history of, or current signs and symptoms of diseases, infections or conditions that in the opinion of the investigator, 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 known allergies, hypersensitivity, or intolerance to ketamine or its excipients
  • Is unable to read and understand the consent forms and patient reported outcomes, complete study-related procedures, and/or communicate with the study staff
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01627782

Locations
United States, Alabama
Birmingham, Alabama, United States
United States, Arkansas
Little Rock, Arkansas, United States
United States, Colorado
Centennial, Colorado, United States
United States, Connecticut
Hartford, Connecticut, United States
New Haven, Connecticut, United States
United States, Georgia
Atlanta, Georgia, United States
United States, Maryland
Rockville, Maryland, United States
United States, New Jersey
Marlton, New Jersey, United States
United States, New York
New York, New York, United States
United States, Pennsylvania
Allentown, Pennsylvania, United States
United States, South Carolina
Charleston, South Carolina, United States
United States, Texas
Dallas, Texas, United States
United States, Utah
Salt Lake City, Utah, United States
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01627782     History of Changes
Other Study ID Numbers: CR100886  KETIVTRD2002 
Study First Received: June 22, 2012
Results First Received: May 10, 2016
Last Updated: June 24, 2016
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Depressive Disorder, Treatment-Resistant
Behavioral Symptoms
Mood Disorders
Mental Disorders
Ketamine
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 23, 2016