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A Study of Ketamine in Patients With Treatment-resistant Depression

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ClinicalTrials.gov Identifier: NCT01627782
Recruitment Status : Completed
First Posted : June 26, 2012
Results First Posted : August 5, 2016
Last Update Posted : August 5, 2016
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Major Depressive Disorder
Interventions Drug: Placebo
Drug: Ketamine
Enrollment 68
Recruitment Details  
Pre-assignment Details A total of 165 participants were screened and 68 participants were randomized into the study. Of these 68 participants randomized, 67 participants received at least 1 dose of the study agent (Intent-To-Treat analysis set).
Arm/Group Title Placebo: 2 Times Per Week Ketamine: 2 Times Per Week Placebo: 3 Times Per Week Ketamine: 3 Times Per Week
Hide Arm/Group Description Participants received Intravenous (IV) infusion of placebo 2 times weekly for 4 weeks. Participants received 0.50 milligram per kilogram (mg/kg) ketamine IV infusion 2 times weekly for 4 weeks. Participants received IV infusion of placebo 3 times weekly for 4 weeks. Participants received 0.50 mg/kg ketamine IV infusion 3 times weekly for 4 weeks.
Period Title: Overall Study
Started 17 18 16 17
Treated 16 18 16 17
Completed 1 12 1 11
Not Completed 16 6 15 6
Reason Not Completed
Adverse Event             1             2             0             1
Lack of Efficacy             11             1             15             2
Protocol Violation             1             0             0             0
Withdrawal by Subject             2             1             0             0
Other             0             2             0             3
Randomized But Not Treated             1             0             0             0
Arm/Group Title Placebo: 2 Times Per Week Ketamine: 2 Times Per Week Placebo: 3 Times Per Week Ketamine: 3 Times Per Week Total
Hide Arm/Group Description Participants received Intravenous (IV) infusion of placebo 2 times weekly for 4 weeks. Participants received 0.50 milligram per kilogram (mg/kg) ketamine IV infusion 2 times weekly for 4 weeks. Participants received IV infusion of placebo 3 times weekly for 4 weeks. Participants received 0.50 mg/kg ketamine IV infusion 3 times weekly for 4 weeks. Total of all reporting groups
Overall Number of Baseline Participants 16 18 16 17 67
Hide Baseline Analysis Population Description
The Intent-To-Treat (ITT) analysis set is defined as participants who were randomized and received at least 1 dose of the study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 16 participants 18 participants 16 participants 17 participants 67 participants
40.3  (11.79) 45.7  (9.58) 46.1  (10.51) 43.3  (11.99) 43.9  (10.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 18 participants 16 participants 17 participants 67 participants
Female
12
  75.0%
12
  66.7%
9
  56.3%
12
  70.6%
45
  67.2%
Male
4
  25.0%
6
  33.3%
7
  43.8%
5
  29.4%
22
  32.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
USA Number Analyzed 16 participants 18 participants 16 participants 17 participants 67 participants
16 18 16 17 67
1.Primary Outcome
Title Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline to Day 15
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
An intent-to-treat (ITT) analysis set is defined as all participants who receive at least 1 dose of study drug and have both Day 1 (baseline) and at least 1 post-baseline MADRS total score. Here,“N”(Number of Participants Analyzed) and “n” signifies those participants who were evaluable for this outcome measure and at given time point, respectively
Arm/Group Title Placebo: 2 Times Per Week Ketamine: 2 Times Per Week Placebo: 3 Times Per Week Ketamine: 3 Times Per Week
Hide Arm/Group Description:
Participants received Intravenous (IV) infusion of placebo 2 times weekly for 4 weeks.
Participants received 0.50 milligram per kilogram (mg/kg) ketamine IV infusion 2 times weekly for 4 weeks.
Participants received IV infusion of placebo 3 times weekly for 4 weeks.
Participants received 0.50 mg/kg ketamine IV infusion 3 times weekly for 4 weeks.
Overall Number of Participants Analyzed 16 18 16 17
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Baseline (n=16,18,16,17) 35.6  (3.79) 33.3  (4.91) 36.8  (5.83) 35.4  (5.28)
Change at Day 15 (n=13,16,16,13) -5.7  (10.23) -18.4  (12.01) -3.1  (5.67) -17.7  (7.27)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo: 2 Times Per Week, Ketamine: 2 Times Per Week
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Mixed Effect Model Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of Least Square Means
Estimated Value -16.0
Confidence Interval (2-Sided) 70%
-20.00 to -12.01
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo: 3 Times Per Week, Ketamine: 3 Times Per Week
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Mixed Effect Model Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of Least Square Means
Estimated Value -16.4
Confidence Interval (2-Sided) 70%
-18.96 to -13.84
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline to Day 29
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
An intent-to-treat (ITT) analysis set is defined as all participants who receive at least 1 dose of study drug and have both Day 1 (baseline) and at least 1 post-baseline MADRS total score. Here,“N”(Number of Participants Analyzed) and “n” signifies those participants who were evaluable for this outcome measure and at given time point, respectively
Arm/Group Title Placebo: 2 Times Per Week Ketamine: 2 Times Per Week Placebo: 3 Times Per Week Ketamine: 3 Times Per Week
Hide Arm/Group Description:
Participants received Intravenous (IV) infusion of placebo 2 times weekly for 4 weeks.
Participants received 0.50 milligram per kilogram (mg/kg) ketamine IV infusion 2 times weekly for 4 weeks.
Participants received IV infusion of placebo 3 times weekly for 4 weeks.
Participants received 0.50 mg/kg ketamine IV infusion 3 times weekly for 4 weeks.
Overall Number of Participants Analyzed 16 18 16 17
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Baseline (n=16,18,16,17) 35.6  (3.79) 33.3  (4.91) 36.8  (5.83) 35.4  (5.28)
Change at Day 29 (n=2,13,1,13) -23.5  (10.61) -27.1  (6.60) -1 [1]   (NA) -22.9  (10.61)
[1]
Standard deviation was not evaluable since only 1 participant was evaluated.
3.Secondary Outcome
Title Number of Responders Based on Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
An intent-to-treat (ITT) analysis set is defined as all participants who receive at least 1 dose of study drug and have both Day 1 (baseline) and at least 1 post-baseline MADRS total score. Here,“N”(Number of Participants Analyzed) and “n” signifies those participants who were evaluable for this outcome measure and at given time point, respectively
Arm/Group Title Placebo: 2 Times Per Week Ketamine: 2 Times Per Week Placebo: 3 Times Per Week Ketamine: 3 Times Per Week
Hide Arm/Group Description:
Participants received Intravenous (IV) infusion of placebo 2 times weekly for 4 weeks.
Participants received 0.50 milligram per kilogram (mg/kg) ketamine IV infusion 2 times weekly for 4 weeks.
Participants received IV infusion of placebo 3 times weekly for 4 weeks.
Participants received 0.50 mg/kg ketamine IV infusion 3 times weekly for 4 weeks.
Overall Number of Participants Analyzed 13 16 16 13
Measure Type: Number
Unit of Measure: Participants
Day 15 (n=13,16,16,13) 2 11 1 7
Day 29 (n=2,13,1,13) 1 13 0 9
4.Secondary Outcome
Title Number of Remitters Based on Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
An intent-to-treat (ITT) analysis set is defined as all participants who receive at least 1 dose of study drug and have both Day 1 (baseline) and at least 1 post-baseline MADRS total score. Here,“N”(Number of Participants Analyzed) and “n” signifies those participants who were evaluable for this outcome measure and at given time point, respectively
Arm/Group Title Placebo: 2 Times Per Week Ketamine: 2 Times Per Week Placebo: 3 Times Per Week Ketamine: 3 Times Per Week
Hide Arm/Group Description:
Participants received Intravenous (IV) infusion of placebo 2 times weekly for 4 weeks.
Participants received 0.50 milligram per kilogram (mg/kg) ketamine IV infusion 2 times weekly for 4 weeks.
Participants received IV infusion of placebo 3 times weekly for 4 weeks.
Participants received 0.50 mg/kg ketamine IV infusion 3 times weekly for 4 weeks.
Overall Number of Participants Analyzed 13 16 16 13
Measure Type: Number
Unit of Measure: Participants
Day 15 (n=13,16,16,13) 1 6 0 3
Day 29 (n=2,13,1,13) 1 12 0 5
5.Secondary Outcome
Title Number of Sustained Responders Based on Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
An intent-to-treat (ITT) analysis set is defined as all participants who receive at least 1 dose of study drug and have both Day 1 (baseline) and at least 1 post-baseline MADRS total score. Here, “N” (Number of Participants Analyzed) signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Placebo: 2 Times Per Week Ketamine: 2 Times Per Week Placebo: 3 Times Per Week Ketamine: 3 Times Per Week
Hide Arm/Group Description:
Participants received Intravenous (IV) infusion of placebo 2 times weekly for 4 weeks.
Participants received 0.50 milligram per kilogram (mg/kg) ketamine IV infusion 2 times weekly for 4 weeks.
Participants received IV infusion of placebo 3 times weekly for 4 weeks.
Participants received 0.50 mg/kg ketamine IV infusion 3 times weekly for 4 weeks.
Overall Number of Participants Analyzed 16 18 16 17
Measure Type: Number
Unit of Measure: Participants
1 7 0 4
6.Secondary Outcome
Title Change in Clinical Global Impression-Severity (CGI-S) Score From Baseline to Endpoint (Day 29)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
An intent-to-treat (ITT) analysis set is defined as all participants who receive at least 1 dose of study drug and have both Day 1 (baseline) and at least 1 post-baseline MADRS total score. Here,“N”(Number of Participants Analyzed) and “n” signifies those participants who were evaluable for this outcome measure and at given time point, respectively
Arm/Group Title Placebo: 2 Times Per Week Ketamine: 2 Times Per Week Placebo: 3 Times Per Week Ketamine: 3 Times Per Week
Hide Arm/Group Description:
Participants received Intravenous (IV) infusion of placebo 2 times weekly for 4 weeks.
Participants received 0.50 milligram per kilogram (mg/kg) ketamine IV infusion 2 times weekly for 4 weeks.
Participants received IV infusion of placebo 3 times weekly for 4 weeks.
Participants received 0.50 mg/kg ketamine IV infusion 3 times weekly for 4 weeks.
Overall Number of Participants Analyzed 15 18 16 17
Median (Full Range)
Unit of Measure: Units on a scale
Baseline (n=15,18,16,17)
5.0
(4 to 6)
5.0
(4 to 6)
5.0
(4 to 6)
5.0
(4 to 6)
Change at Endpoint (n=15,18,16,17)
0.0
(-4 to 0)
-2.0
(-4 to 1)
0.0
(-1 to 1)
-2.0
(-4 to 0)
7.Secondary Outcome
Title Clinical Global Impression of Improvement (CGI-I) Score at Endpoint of Double Blind Phase
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
An intent-to-treat (ITT) analysis set is defined as all participants who receive at least 1 dose of study drug and have both Day 1 (baseline) and at least 1 post-baseline MADRS total score. Here,“N”(Number of Participants Analyzed) signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Placebo: 2 Times Per Week Ketamine: 2 Times Per Week Placebo: 3 Times Per Week Ketamine: 3 Times Per Week
Hide Arm/Group Description:
Participants received Intravenous (IV) infusion of placebo 2 times weekly for 4 weeks.
Participants received 0.50 milligram per kilogram (mg/kg) ketamine IV infusion 2 times weekly for 4 weeks.
Participants received IV infusion of placebo 3 times weekly for 4 weeks.
Participants received 0.50 mg/kg ketamine IV infusion 3 times weekly for 4 weeks.
Overall Number of Participants Analyzed 16 18 16 17
Median (Full Range)
Unit of Measure: Units on a scale
4.0
(1 to 5)
2.0
(1 to 5)
4.0
(2 to 5)
2.0
(1 to 5)
8.Secondary Outcome
Title Change in Patient Global Impression-Severity (PGI-S) Score From Baseline to Endpoint (Day 29)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
An intent-to-treat (ITT) analysis set is defined as all participants who receive at least 1 dose of study drug and have both Day 1 (baseline) and at least 1 post-baseline MADRS total score. Here,“N”(Number of Participants Analyzed) and “n” signifies those participants who were evaluable for this outcome measure and at given time point, respectively
Arm/Group Title Placebo: 2 Times Per Week Ketamine: 2 Times Per Week Placebo: 3 Times Per Week Ketamine: 3 Times Per Week
Hide Arm/Group Description:
Participants received Intravenous (IV) infusion of placebo 2 times weekly for 4 weeks.
Participants received 0.50 milligram per kilogram (mg/kg) ketamine IV infusion 2 times weekly for 4 weeks.
Participants received IV infusion of placebo 3 times weekly for 4 weeks.
Participants received 0.50 mg/kg ketamine IV infusion 3 times weekly for 4 weeks.
Overall Number of Participants Analyzed 15 18 16 17
Median (Full Range)
Unit of Measure: Units on a scale
Baseline (n=15,18,16,17)
8.0
(4 to 9)
7.5
(5 to 9)
8.0
(5 to 10)
7.0
(5 to 9)
Change at Endpoint (n=15,18,16,17)
0.0
(-3 to 2)
-4.0
(-8 to 0)
-1.0
(-3 to 1)
-3.0
(-8 to 1)
9.Secondary Outcome
Title Patient Global Impression-Change (PGI-C) Score at Endpoint of Double Blind Phase
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
An intent-to-treat (ITT) analysis set is defined as all participants who receive at least 1 dose of study drug and have both Day 1 (baseline) and at least 1 post-baseline MADRS total score. Here,“N”(Number of Participants Analyzed) signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Placebo: 2 Times Per Week Ketamine: 2 Times Per Week Placebo: 3 Times Per Week Ketamine: 3 Times Per Week
Hide Arm/Group Description:
Participants received Intravenous (IV) infusion of placebo 2 times weekly for 4 weeks.
Participants received 0.50 milligram per kilogram (mg/kg) ketamine IV infusion 2 times weekly for 4 weeks.
Participants received IV infusion of placebo 3 times weekly for 4 weeks.
Participants received 0.50 mg/kg ketamine IV infusion 3 times weekly for 4 weeks.
Overall Number of Participants Analyzed 16 18 16 17
Median (Full Range)
Unit of Measure: Units on a scale
4.0
(2 to 6)
2.0
(1 to 4)
4.0
(3 to 6)
3.0
(1 to 4)
10.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of Ketamine
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
An intent-to-treat (ITT) analysis set is defined as all participants who receive at least 1 dose of study drug and have both Day 1 (baseline) and at least 1 post-baseline MADRS total score. Here,“N”(Number of Participants Analyzed) and “n” signifies those participants who were evaluable for this outcome measure and at given time point, respectively
Arm/Group Title Ketamine: 2 Times Per Week Ketamine: 3 Times Per Week
Hide Arm/Group Description:
Participants received 0.50 milligram per kilogram (mg/kg) ketamine IV infusion 2 times weekly for 4 weeks.
Participants received 0.50 mg/kg ketamine IV infusion 3 times weekly for 4 weeks.
Overall Number of Participants Analyzed 16 16
Mean (Standard Deviation)
Unit of Measure: nanogram per milliliter (ng/ml)
Day 1 (n=16,16) 207  (83.0) 168  (34.4)
Day 15 (n=14,15) 219  (69.4) 189  (74.4)
11.Secondary Outcome
Title Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ketamine
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
An intent-to-treat (ITT) analysis set is defined as all participants who receive at least 1 dose of study drug and have both Day 1 (baseline) and at least 1 post-baseline MADRS total score. Here,“N”(Number of Participants Analyzed) and “n” signifies those participants who were evaluable for this outcome measure and at given time point, respectively
Arm/Group Title Ketamine: 2 Times Per Week Ketamine: 3 Times Per Week
Hide Arm/Group Description:
Participants received 0.50 milligram per kilogram (mg/kg) ketamine IV infusion 2 times weekly for 4 weeks.
Participants received 0.50 mg/kg ketamine IV infusion 3 times weekly for 4 weeks.
Overall Number of Participants Analyzed 16 16
Median (Full Range)
Unit of Measure: Hour
Day 1 (n=16,16)
0.67
(0.63 to 0.83)
0.66
(0.33 to 0.75)
Day 15 (n=14,15)
0.67
(0.63 to 1.00)
0.67
(0.5 to 0.83)
12.Secondary Outcome
Title Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC[0-last])
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
An intent-to-treat (ITT) analysis set is defined as all participants who receive at least 1 dose of study drug and have both Day 1 (baseline) and at least 1 post-baseline MADRS total score. Here,“N”(Number of Participants Analyzed) and “n” signifies those participants who were evaluable for this outcome measure and at given time point, respectively
Arm/Group Title Ketamine: 2 Times Per Week Ketamine: 3 Times Per Week
Hide Arm/Group Description:
Participants received 0.50 milligram per kilogram (mg/kg) ketamine IV infusion 2 times weekly for 4 weeks.
Participants received 0.50 mg/kg ketamine IV infusion 3 times weekly for 4 weeks.
Overall Number of Participants Analyzed 16 15
Mean (Standard Deviation)
Unit of Measure: hour*nanogram per milliliter
Day 1 (n=16,15) 312  (67.9) 295  (42.8)
Day 15 (n=14,14) 342  (66.7) 293  (65.6)
13.Secondary Outcome
Title Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity])
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
An intent-to-treat (ITT) analysis set is defined as all participants who receive at least 1 dose of study drug and have both Day 1 (baseline) and at least 1 post-baseline MADRS total score. Here,“N”(Number of Participants Analyzed) and “n” signifies those participants who were evaluable for this outcome measure and at given time point, respectively
Arm/Group Title Ketamine: 2 Times Per Week Ketamine: 3 Times Per Week
Hide Arm/Group Description:
Participants received 0.50 milligram per kilogram (mg/kg) ketamine IV infusion 2 times weekly for 4 weeks.
Participants received 0.50 mg/kg ketamine IV infusion 3 times weekly for 4 weeks.
Overall Number of Participants Analyzed 13 13
Mean (Standard Deviation)
Unit of Measure: hour*nanogram per milliliter
Day 1 (n=13,13) 369  (79.9) 344  (47.3)
Day 15 (n=9,8) 416  (68.9) 340  (94.0)
14.Secondary Outcome
Title Total Systemic Clearance (CL) of Ketamine
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
An intent-to-treat (ITT) analysis set is defined as all participants who receive at least 1 dose of study drug and have both Day 1 (baseline) and at least 1 post-baseline MADRS total score. Here,“N”(Number of Participants Analyzed) and “n” signifies those participants who were evaluable for this outcome measure and at given time point, respectively
Arm/Group Title Ketamine: 2 Times Per Week Ketamine: 3 Times Per Week
Hide Arm/Group Description:
Participants received 0.50 milligram per kilogram (mg/kg) ketamine IV infusion 2 times weekly for 4 weeks.
Participants received 0.50 mg/kg ketamine IV infusion 3 times weekly for 4 weeks.
Overall Number of Participants Analyzed 13 13
Mean (Standard Deviation)
Unit of Measure: liter per hour
Day 1 (n=13,13) 113  (35.1) 108  (21.4)
Day 15 (n=9,8) 93.9  (15.6) 117  (22.3)
15.Secondary Outcome
Title Volume of Distribution at Steady-State (Vss) of Ketamine
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
An intent-to-treat (ITT) analysis set is defined as all participants who receive at least 1 dose of study drug and have both Day 1 (baseline) and at least 1 post-baseline MADRS total score. Here,“N”(Number of Participants Analyzed) and “n” signifies those participants who were evaluable for this outcome measure and at given time point, respectively
Arm/Group Title Ketamine: 2 Times Per Week Ketamine: 3 Times Per Week
Hide Arm/Group Description:
Participants received 0.50 milligram per kilogram (mg/kg) ketamine IV infusion 2 times weekly for 4 weeks.
Participants received 0.50 mg/kg ketamine IV infusion 3 times weekly for 4 weeks.
Overall Number of Participants Analyzed 13 13
Mean (Standard Deviation)
Unit of Measure: liter
Day 1 (n=13,13) 275  (114) 276  (77.2)
Day 15 (n=9,8) 239  (61.2) 290  (64.9)
16.Secondary Outcome
Title Elimination Half-Life (t1/2)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
An intent-to-treat (ITT) analysis set is defined as all participants who receive at least 1 dose of study drug and have both Day 1 (baseline) and at least 1 post-baseline MADRS total score. Here,“N”(Number of Participants Analyzed) and “n” signifies those participants who were evaluable for this outcome measure and at given time point, respectively
Arm/Group Title Ketamine: 2 Times Per Week Ketamine: 3 Times Per Week
Hide Arm/Group Description:
Participants received 0.50 milligram per kilogram (mg/kg) ketamine IV infusion 2 times weekly for 4 weeks.
Participants received 0.50 mg/kg ketamine IV infusion 3 times weekly for 4 weeks.
Overall Number of Participants Analyzed 13 13
Mean (Standard Deviation)
Unit of Measure: hour
Day 1 (n=13,13) 2.18  (0.43) 2.18  (0.40)
Day 15 (n=9,8) 2.39  (0.36) 2.21  (0.36)
Time Frame Screening up to Follow up (3 Weeks After Last Dose of Study Drug Administration)
Adverse Event Reporting Description The safety analysis set is defined as all participants who received at least 1 dose of the study drug.
 
Arm/Group Title Placebo: 2 Times Per Week Ketamine: 2 Times Per Week Placebo: 3 Times Per Week Ketamine: 3 Times Per Week
Hide Arm/Group Description Participants received Intravenous (IV) infusion of placebo 2 times weekly for 4 weeks. Participants received 0.50 milligram per kilogram (mg/kg) ketamine IV infusion 2 times weekly for 4 weeks. Participants received IV infusion of placebo 3 times weekly for 4 weeks. Participants received 0.50 mg/kg ketamine IV infusion 3 times weekly for 4 weeks.
All-Cause Mortality
Placebo: 2 Times Per Week Ketamine: 2 Times Per Week Placebo: 3 Times Per Week Ketamine: 3 Times Per Week
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo: 2 Times Per Week Ketamine: 2 Times Per Week Placebo: 3 Times Per Week Ketamine: 3 Times Per Week
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/16 (0.00%)   2/18 (11.11%)   0/16 (0.00%)   0/17 (0.00%) 
Psychiatric disorders         
Anxiety * 1  0/16 (0.00%)  1/18 (5.56%)  0/16 (0.00%)  0/17 (0.00%) 
Suicide Attempt * 1  0/16 (0.00%)  1/18 (5.56%)  0/16 (0.00%)  0/17 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA Version 16.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo: 2 Times Per Week Ketamine: 2 Times Per Week Placebo: 3 Times Per Week Ketamine: 3 Times Per Week
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   9/16 (56.25%)   15/18 (83.33%)   8/16 (50.00%)   13/17 (76.47%) 
Cardiac disorders         
Cardiac Flutter * 1  0/16 (0.00%)  0/18 (0.00%)  1/16 (6.25%)  0/17 (0.00%) 
Palpitations * 1  0/16 (0.00%)  1/18 (5.56%)  1/16 (6.25%)  0/17 (0.00%) 
Ventricular Extrasystoles * 1  0/16 (0.00%)  0/18 (0.00%)  1/16 (6.25%)  0/17 (0.00%) 
Ear and labyrinth disorders         
Hyperacusis * 1  0/16 (0.00%)  1/18 (5.56%)  0/16 (0.00%)  0/17 (0.00%) 
Eye disorders         
Altered Visual Depth Perception * 1  0/16 (0.00%)  0/18 (0.00%)  0/16 (0.00%)  1/17 (5.88%) 
Diplopia * 1  0/16 (0.00%)  1/18 (5.56%)  0/16 (0.00%)  0/17 (0.00%) 
Vision Blurred * 1  0/16 (0.00%)  2/18 (11.11%)  0/16 (0.00%)  0/17 (0.00%) 
Gastrointestinal disorders         
Abdominal Discomfort * 1  0/16 (0.00%)  0/18 (0.00%)  0/16 (0.00%)  1/17 (5.88%) 
Abdominal Pain Upper * 1  1/16 (6.25%)  0/18 (0.00%)  0/16 (0.00%)  0/17 (0.00%) 
Constipation * 1  0/16 (0.00%)  1/18 (5.56%)  0/16 (0.00%)  0/17 (0.00%) 
Diarrhoea * 1  0/16 (0.00%)  0/18 (0.00%)  0/16 (0.00%)  1/17 (5.88%) 
Dyspepsia * 1  0/16 (0.00%)  0/18 (0.00%)  0/16 (0.00%)  1/17 (5.88%) 
Hypoaesthesia Oral * 1  0/16 (0.00%)  1/18 (5.56%)  0/16 (0.00%)  1/17 (5.88%) 
Nausea * 1  1/16 (6.25%)  3/18 (16.67%)  2/16 (12.50%)  4/17 (23.53%) 
Paraesthesia Oral * 1  0/16 (0.00%)  1/18 (5.56%)  0/16 (0.00%)  0/17 (0.00%) 
Vomiting * 1  0/16 (0.00%)  1/18 (5.56%)  0/16 (0.00%)  0/17 (0.00%) 
General disorders         
Fatigue * 1  0/16 (0.00%)  0/18 (0.00%)  0/16 (0.00%)  2/17 (11.76%) 
Feeling Abnormal * 1  0/16 (0.00%)  1/18 (5.56%)  0/16 (0.00%)  1/17 (5.88%) 
Feeling Cold * 1  0/16 (0.00%)  0/18 (0.00%)  0/16 (0.00%)  1/17 (5.88%) 
Inflammation * 1  0/16 (0.00%)  1/18 (5.56%)  0/16 (0.00%)  0/17 (0.00%) 
Infusion Site Pain * 1  0/16 (0.00%)  1/18 (5.56%)  0/16 (0.00%)  1/17 (5.88%) 
Injection Site Extravasation * 1  0/16 (0.00%)  0/18 (0.00%)  1/16 (6.25%)  0/17 (0.00%) 
Irritability * 1  0/16 (0.00%)  1/18 (5.56%)  0/16 (0.00%)  0/17 (0.00%) 
Infections and infestations         
Groin Abscess * 1  0/16 (0.00%)  0/18 (0.00%)  0/16 (0.00%)  1/17 (5.88%) 
Pharyngitis * 1  0/16 (0.00%)  1/18 (5.56%)  0/16 (0.00%)  0/17 (0.00%) 
Urinary Tract Infection * 1  0/16 (0.00%)  0/18 (0.00%)  1/16 (6.25%)  1/17 (5.88%) 
Injury, poisoning and procedural complications         
Animal Bite * 1  0/16 (0.00%)  1/18 (5.56%)  0/16 (0.00%)  0/17 (0.00%) 
Ligament Sprain * 1  0/16 (0.00%)  0/18 (0.00%)  1/16 (6.25%)  0/17 (0.00%) 
Wound * 1  0/16 (0.00%)  1/18 (5.56%)  0/16 (0.00%)  0/17 (0.00%) 
Investigations         
Blood Potassium Decreased * 1  0/16 (0.00%)  0/18 (0.00%)  0/16 (0.00%)  1/17 (5.88%) 
Blood Pressure Increased * 1  0/16 (0.00%)  2/18 (11.11%)  0/16 (0.00%)  0/17 (0.00%) 
Drug Screen Positive * 1  1/16 (6.25%)  0/18 (0.00%)  0/16 (0.00%)  0/17 (0.00%) 
Electrocardiogram St-T Change * 1  0/16 (0.00%)  0/18 (0.00%)  0/16 (0.00%)  1/17 (5.88%) 
Weight Decreased * 1  0/16 (0.00%)  0/18 (0.00%)  1/16 (6.25%)  0/17 (0.00%) 
Metabolism and nutrition disorders         
Fluid Retention * 1  1/16 (6.25%)  0/18 (0.00%)  0/16 (0.00%)  0/17 (0.00%) 
Musculoskeletal and connective tissue disorders         
Bone Pain * 1  0/16 (0.00%)  1/18 (5.56%)  0/16 (0.00%)  0/17 (0.00%) 
Intervertebral Disc Degeneration * 1  1/16 (6.25%)  0/18 (0.00%)  0/16 (0.00%)  0/17 (0.00%) 
Nervous system disorders         
Amnesia * 1  1/16 (6.25%)  0/18 (0.00%)  0/16 (0.00%)  0/17 (0.00%) 
Cognitive Disorder * 1  0/16 (0.00%)  0/18 (0.00%)  0/16 (0.00%)  1/17 (5.88%) 
Dizziness * 1  1/16 (6.25%)  4/18 (22.22%)  0/16 (0.00%)  2/17 (11.76%) 
Dizziness Postural * 1  1/16 (6.25%)  0/18 (0.00%)  0/16 (0.00%)  0/17 (0.00%) 
Dysarthria * 1  0/16 (0.00%)  1/18 (5.56%)  0/16 (0.00%)  0/17 (0.00%) 
Dysgeusia * 1  0/16 (0.00%)  1/18 (5.56%)  0/16 (0.00%)  1/17 (5.88%) 
Headache * 1  5/16 (31.25%)  4/18 (22.22%)  1/16 (6.25%)  7/17 (41.18%) 
Hypoaesthesia * 1  0/16 (0.00%)  2/18 (11.11%)  0/16 (0.00%)  3/17 (17.65%) 
Migraine * 1  0/16 (0.00%)  0/18 (0.00%)  1/16 (6.25%)  0/17 (0.00%) 
Paraesthesia * 1  0/16 (0.00%)  1/18 (5.56%)  0/16 (0.00%)  2/17 (11.76%) 
Poor Quality Sleep * 1  0/16 (0.00%)  1/18 (5.56%)  0/16 (0.00%)  0/17 (0.00%) 
Sedation * 1  0/16 (0.00%)  1/18 (5.56%)  0/16 (0.00%)  1/17 (5.88%) 
Somnolence * 1  0/16 (0.00%)  1/18 (5.56%)  0/16 (0.00%)  0/17 (0.00%) 
Psychiatric disorders         
Agitation * 1  1/16 (6.25%)  0/18 (0.00%)  0/16 (0.00%)  0/17 (0.00%) 
Anxiety * 1  0/16 (0.00%)  4/18 (22.22%)  0/16 (0.00%)  1/17 (5.88%) 
Depression * 1  0/16 (0.00%)  0/18 (0.00%)  1/16 (6.25%)  0/17 (0.00%) 
Disorientation * 1  1/16 (6.25%)  0/18 (0.00%)  0/16 (0.00%)  0/17 (0.00%) 
Dissociation * 1  0/16 (0.00%)  5/18 (27.78%)  0/16 (0.00%)  1/17 (5.88%) 
Dissociative Disorder * 1  0/16 (0.00%)  1/18 (5.56%)  0/16 (0.00%)  0/17 (0.00%) 
Euphoric Mood * 1  0/16 (0.00%)  1/18 (5.56%)  0/16 (0.00%)  1/17 (5.88%) 
Hallucination, Tactile * 1  0/16 (0.00%)  1/18 (5.56%)  0/16 (0.00%)  0/17 (0.00%) 
Hallucination, Visual * 1  0/16 (0.00%)  1/18 (5.56%)  0/16 (0.00%)  1/17 (5.88%) 
Insomnia * 1  1/16 (6.25%)  0/18 (0.00%)  1/16 (6.25%)  0/17 (0.00%) 
Nightmare * 1  0/16 (0.00%)  1/18 (5.56%)  0/16 (0.00%)  0/17 (0.00%) 
Paranoia * 1  0/16 (0.00%)  1/18 (5.56%)  0/16 (0.00%)  1/17 (5.88%) 
Restlessness * 1  0/16 (0.00%)  1/18 (5.56%)  0/16 (0.00%)  0/17 (0.00%) 
Renal and urinary disorders         
Dysuria * 1  1/16 (6.25%)  0/18 (0.00%)  0/16 (0.00%)  0/17 (0.00%) 
Micturition Urgency * 1  0/16 (0.00%)  0/18 (0.00%)  0/16 (0.00%)  1/17 (5.88%) 
Respiratory, thoracic and mediastinal disorders         
Asthma * 1  0/16 (0.00%)  0/18 (0.00%)  1/16 (6.25%)  0/17 (0.00%) 
Dyspnoea * 1  0/16 (0.00%)  1/18 (5.56%)  0/16 (0.00%)  0/17 (0.00%) 
Nasal Congestion * 1  0/16 (0.00%)  0/18 (0.00%)  1/16 (6.25%)  0/17 (0.00%) 
Respiratory Distress * 1  0/16 (0.00%)  1/18 (5.56%)  0/16 (0.00%)  0/17 (0.00%) 
Skin and subcutaneous tissue disorders         
Acne * 1  1/16 (6.25%)  0/18 (0.00%)  0/16 (0.00%)  0/17 (0.00%) 
Dermatitis Contact * 1  1/16 (6.25%)  0/18 (0.00%)  0/16 (0.00%)  0/17 (0.00%) 
Pruritus * 1  0/16 (0.00%)  1/18 (5.56%)  0/16 (0.00%)  0/17 (0.00%) 
Rash * 1  0/16 (0.00%)  0/18 (0.00%)  1/16 (6.25%)  0/17 (0.00%) 
Urticaria * 1  0/16 (0.00%)  1/18 (5.56%)  0/16 (0.00%)  0/17 (0.00%) 
Vascular disorders         
Hypertension * 1  0/16 (0.00%)  2/18 (11.11%)  0/16 (0.00%)  1/17 (5.88%) 
Orthostatic Hypotension * 1  0/16 (0.00%)  0/18 (0.00%)  0/16 (0.00%)  1/17 (5.88%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA Version 16.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Director, Clinical Research
Organization: Janssen Research & Development, LLC
EMail: ClinicalTrialDisclosure@its.jnj.com
Layout table for additonal information
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01627782     History of Changes
Other Study ID Numbers: CR100886
KETIVTRD2002 ( Other Identifier: Janssen Research & Development, LLC )
First Submitted: June 22, 2012
First Posted: June 26, 2012
Results First Submitted: May 10, 2016
Results First Posted: August 5, 2016
Last Update Posted: August 5, 2016