Back to resultsA Study of Ketamine in Patients With Treatment-resistant Depression
Primary Purpose
Major Depressive Disorder
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Placebo
Ketamine
Sponsored by
About this trial
This is an interventional treatment trial for Major Depressive Disorder focused on measuring Major depressive disorder, Treatment-resistant depression, Ketamine
Eligibility 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Placebo Comparator
Experimental
Experimental
Placebo Comparator
Arm Label
Placebo 3 times/week
Ketamine 3 times/week
Ketamine 2 times/week
Placebo 2 times/week
Arm Description
Outcomes
Primary Outcome Measures
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline to 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.
Secondary Outcome Measures
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline to Day 29
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
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
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
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)
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
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)
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
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
The Cmax is the maximum observed plasma concentration of drug.
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ketamine
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])
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])
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
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
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)
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).
Full Information
NCT ID
NCT01627782
First Posted
June 22, 2012
Last Updated
May 18, 2020
Sponsor
Janssen Research & Development, LLC
1. Study Identification
Unique Protocol Identification Number
NCT01627782
Brief Title
A Study of Ketamine in Patients With Treatment-resistant Depression
Official Title
A Double-blind, Randomized, Placebo-controlled, Parallel Group, Dose Frequency Study of Ketamine in Subjects With Treatment-resistant Depression
Study Type
Interventional
2. Study Status
Record Verification Date
May 2020
Overall Recruitment Status
Completed
Study Start Date
August 6, 2012 (Actual)
Primary Completion Date
September 12, 2013 (Actual)
Study Completion Date
September 12, 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
5. Study Description
Brief Summary
The purpose of this study is to explore the optimal dose frequency of ketamine in patients with treatment-resistant depression (TRD).
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.
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, Ketamine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
68 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo 3 times/week
Arm Type
Placebo Comparator
Arm Title
Ketamine 3 times/week
Arm Type
Experimental
Arm Title
Ketamine 2 times/week
Arm Type
Experimental
Arm Title
Placebo 2 times/week
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Form= intravenous infusion, route= intravenous (IV) use. IV infusions of placebo 2 times weekly or IV infusions of placebo 3 times weekly.
Intervention Type
Drug
Intervention Name(s)
Ketamine
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline to Day 15
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
Baseline (Day 1) and Day 15
Secondary Outcome Measure Information:
Title
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline to Day 29
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
Baseline (Day 1) and Day 29
Title
Number of Responders Based on Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Description
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.
Time Frame
Day 15 and Day 29
Title
Number of Remitters Based on Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Description
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.
Time Frame
Day 15 and Day 29
Title
Number of Sustained Responders Based on Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Description
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.
Time Frame
Day 15
Title
Change in Clinical Global Impression-Severity (CGI-S) Score From Baseline to Endpoint (Day 29)
Description
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.
Time Frame
Baseline (Day 1) and Endpoint (Day 29)
Title
Clinical Global Impression of Improvement (CGI-I) Score at Endpoint of Double Blind Phase
Description
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.
Time Frame
Endpoint (Day 29)
Title
Change in Patient Global Impression-Severity (PGI-S) Score From Baseline to Endpoint (Day 29)
Description
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.
Time Frame
Baseline (Day 1) and Endpoint (Day 29)
Title
Patient Global Impression-Change (PGI-C) Score at Endpoint of Double Blind Phase
Description
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.
Time Frame
Endpoint (Day 29)
Title
Maximum Observed Plasma Concentration (Cmax) of Ketamine
Description
The Cmax is the maximum observed plasma concentration of drug.
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
Title
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ketamine
Description
The Tmax is defined as actual sampling time to reach maximum observed drug concentration.
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
Title
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC[0-last])
Description
The AUC(0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.
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
Title
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity])
Description
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.
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
Title
Total Systemic Clearance (CL) of Ketamine
Description
The CL is a quantitative measure of the rate at which a drug substance is removed from the body.
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
Title
Volume of Distribution at Steady-State (Vss) of Ketamine
Description
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.
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
Title
Elimination Half-Life (t1/2)
Description
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).
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
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 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
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
Birmingham
State/Province
Alabama
Country
United States
City
Little Rock
State/Province
Arkansas
Country
United States
City
Centennial
State/Province
Colorado
Country
United States
City
Hartford
State/Province
Connecticut
Country
United States
City
New Haven
State/Province
Connecticut
Country
United States
City
Atlanta
State/Province
Georgia
Country
United States
City
Rockville
State/Province
Maryland
Country
United States
City
Marlton
State/Province
New Jersey
Country
United States
City
New York
State/Province
New York
Country
United States
City
Allentown
State/Province
Pennsylvania
Country
United States
City
Charleston
State/Province
South Carolina
Country
United States
City
Dallas
State/Province
Texas
Country
United States
City
Salt Lake City
State/Province
Utah
Country
United States
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
Links:
URL
https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217051&parentIdentifier=CR100886&attachmentIdentifier=7d6ebba0-1b0a-4df6-96fd-421b53fdb5b7&fileName=KETIVTRD2002_(CR100886)_Additional_results_data_CH.pdf&versionIdentifier=
Description
A Double-blind, Randomized, Placebo-controlled, Parallel Group, Dose Frequency Study of Ketamine in Subjects With Treatment-resistant Depression
Learn more about this trial
A Study of Ketamine in Patients With Treatment-resistant Depression
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