Clinical trial NCT01627782: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Major Depressive Disorder
Keywords: Major depressive disorder
Treatment-resistant depression
Ketamine
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2012-06-26
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline to Day 15
timeFrame: Baseline (Day 1) and Day 15
Secondary outcomes:
measure: Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline to Day 29
timeFrame: Baseline (Day 1) and Day 29
measure: Number of Responders Based on Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
timeFrame: Day 15 and Day 29
measure: Number of Remitters Based on Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
timeFrame: Day 15 and Day 29
measure: Number of Sustained Responders Based on Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
timeFrame: Day 15
measure: Change in Clinical Global Impression-Severity (CGI-S) Score From Baseline to Endpoint (Day 29)
timeFrame: Baseline (Day 1) and Endpoint (Day 29)
measure: Clinical Global Impression of Improvement (CGI-I) Score at Endpoint of Double Blind Phase
timeFrame: Endpoint (Day 29)
measure: Change in Patient Global Impression-Severity (PGI-S) Score From Baseline to Endpoint (Day 29)
timeFrame: Baseline (Day 1) and Endpoint (Day 29)
measure: Patient Global Impression-Change (PGI-C) Score at Endpoint of Double Blind Phase
timeFrame: Endpoint (Day 29)
measure: Maximum Observed Plasma Concentration (Cmax) of Ketamine
timeFrame: 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
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ketamine
timeFrame: 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
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC[0-last])
timeFrame: 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
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity])
timeFrame: 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
measure: Total Systemic Clearance (CL) of Ketamine
timeFrame: 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
measure: Volume of Distribution at Steady-State (Vss) of Ketamine
timeFrame: 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
measure: Elimination Half-Life (t1/2)
timeFrame: 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
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Little Rock
country: United States
state: Arkansas
city: Centennial
country: United States
state: Colorado
city: Hartford
country: United States
state: Connecticut
city: New Haven
country: United States
state: Connecticut
city: Atlanta
country: United States
state: Georgia
city: Rockville
country: United States
state: Maryland
city: Marlton
country: United States
state: New Jersey
city: New York
country: United States
state: New York
city: Allentown
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Dallas
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
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.
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.