A Study of Ketamine in Patients With Treatment-resistant Depression

Major Depressive Disorder Clinical Trial

Official title:

A Double-blind, Randomized, Placebo-controlled, Parallel Group, Dose Frequency Study of Ketamine in Subjects With Treatment-resistant Depression

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01627782
• Other study ID #: CR100886
• Secondary ID: KETIVTRD2002
• Status: Completed
• Phase: Phase 2
• Start date: August 6, 2012
• Est. completion date: September 12, 2013

Study information

• Verified date: May 2020
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to explore the optimal dose frequency of ketamine in patients with treatment-resistant depression (TRD).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: September 12, 2013
• Est. primary completion date: September 12, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

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

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Depressive Disorder, Treatment-Resistant
• Major Depressive Disorder

Intervention

Drug:
• Placebo
Form= intravenous infusion, route= intravenous (IV) use. IV infusions of placebo 2 times weekly or IV infusions of placebo 3 times weekly.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline (Day 1) and Day 15
Secondary	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.	Baseline (Day 1) and Day 29
Secondary	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.	Day 15 and Day 29
Secondary	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.	Day 15 and Day 29
Secondary	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.	Day 15
Secondary	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.	Baseline (Day 1) and Endpoint (Day 29)
Secondary	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.	Endpoint (Day 29)
Secondary	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.	Baseline (Day 1) and Endpoint (Day 29)
Secondary	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.	Endpoint (Day 29)
Secondary	Maximum Observed Plasma Concentration (Cmax) of Ketamine	The Cmax is the maximum observed plasma concentration of drug.	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
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ketamine	The Tmax is defined as actual sampling time to reach maximum observed drug concentration.	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
Secondary	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.	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
Secondary	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.	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
Secondary	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.	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
Secondary	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.	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
Secondary	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).	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

External Links

•   A Double-blind, Randomized, Placebo-controlled, Parallel Group, Dose Frequency Study of Ketamine in Subjects With Treatment-resistant Depression