Clinical trial NCT04599855: A Study of Esketamine Nasal Spray, Administered as Monotherapy, in Adult Participants With Treatment-resistant Depression
Official title: A Randomized, Double-blind, Multicenter, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Esketamine Nasal Spray, Administered as Monotherapy, in Adult Participants With Treatment-resistant Depression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Depressive Disorder, Treatment-Resistant
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2020-10-23
Enrollment: 477
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy of each individual dose of esketamine nasal spray, 56 milligram (mg) and 84 mg, compared with placebo nasal spray in improving depressive symptoms in participants with treatment resistant depression (TRD), as assessed by the change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) total score from Day 1 (prerandomization) to the end of the 4 week double-blind treatment phase (Day 28).


Eligibility criteria: Inclusion Criteria:

* Participant must meet the Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-5) diagnostic criteria for single-episode MDD or recurrent MDD, without psychotic features, based upon clinical assessment and confirmed by the MINI. Participants 65 years of age or older must have had the first onset of depression prior to 55 years of age
* Participant must have had nonresponse (\<=25% improvement) to \>=2 oral antidepressant treatments in the current episode of depression, assessed using the MGH-ATRQ, and confirmed by documented records (example, medical/pharmacy/prescription records or a letter from a treating physician)
* Participant must have an Inventory of Depressive Symptomatology-Clinician rated, 30-item (IDS-C30) total score of \>=34
* The participant's current major depressive episode, depression symptom severity, and antidepressant treatment response in the current depressive episode, must be confirmed by the State vs. Trait, Assessibility, Face Validity, Ecological Validity, Rule of Three P's (SAFER) Interview
* Participant must be medically stable on the basis of physical examination, medical history, vital signs (including blood pressure), and 12-lead electrocardiogram (ECG) performed in the screening phase. If there are any abnormalities that are not specified in the inclusion and exclusion criteria, the determination of their clinical significance must be determined by the investigator and recorded in the participant's source documents and initiated by the investigator
* Participant must be medically stable on the basis of clinical laboratory tests performed in the screening phase. If the results of the serum chemistry panel, hematology, or urinalysis are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study. This determination must be recorded in the participant's source documents and initialed by the investigator: (a) Participants with a pre-existing history of thyroid disease/disorder who are treated with thyroid hormones must be on a stable dosage for 3 months prior to the start of the screening phase; (b) For any participant (regardless of thyroid history), if the thyroid-stimulating hormone (TSH) value is out of range, a free thyroxine (FT4) will be conducted. If the FT4 value is abnormal and considered to be clinically significant (after discussion with the medical monitor), the participant is not eligible
* Participant must be comfortable with self-administration of nasal spray medication and be able to follow the nasal spray administration instructions provided

Exclusion Criteria:

* The participant has used ketamine/esketamine (lifetime)
* The participant's depressive symptoms have previously demonstrated nonresponse to an adequate course of treatment with electroconvulsive therapy (ECT) in the current major depressive episode, defined as at least 7 treatments with unilateral/bilateral ECT
* Participant has received vagal nerve stimulation (VNS) or has received deep brain stimulation (DBS) in the current episode of depression
* Participant has a current or history of seizures (uncomplicated childhood febrile seizures with no sequelae are not exclusionary)
* Participant has any anatomical or medical condition that, per the investigator's clinical judgment based on assessment, may impede delivery or absorption of nasal spray study drug

Primary outcomes:
measure: Double-blind Treatment Phase: Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Day 1 (Pre-randomization) to Day 28
timeFrame: Day 1 (pre-randomization) to Day 28 (end of DB treatment phase)
Secondary outcomes:
measure: Double-blind Treatment Phase: Change in MADRS Total Score From Day 1 (Pre-randomization) to Day 2 (24 Hours Post First Dose on Day 1)
timeFrame: Day 1 (pre-randomization) to Day 2 of DB treatment phase (24 hours post first dose on Day 1)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB Department of Psychiatry and Behavioral Neurobiology
state: Alabama
city: Huntsville
country: United States
facility: UAB Huntsville Regional Medical Campus
state: Alabama
city: Little Rock
country: United States
facility: Preferred Research Partners
state: Arkansas
city: Glendale
country: United States
facility: Behavioral Research Specialists LLC
state: California
city: Los Angeles
country: United States
facility: CalNeuro Research
state: California
city: Oakland
country: United States
facility: Pacific Research Partners
state: California
city: Redlands
country: United States
facility: Anderson Clinical Research
state: California
city: San Diego
country: United States
facility: University of California at San Diego
state: California
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: San Francisco
country: United States
facility: UCSF Nancy Friend Pritzker Psychiatry Building
state: California
city: Santa Ana
country: United States
facility: Velocity Clinical Research
state: California
city: Santee
country: United States
facility: CMB Clinical Trials
state: California
city: Farmington
country: United States
facility: University of Connecticut Health Center
state: Connecticut
city: Hallandale Beach
country: United States
facility: Velocity Clinical Research, Hallandale Beach
state: Florida
city: Lakeland
country: United States
facility: Accel Research Sites
state: Florida
city: Orlando
country: United States
facility: APG Research LLC
state: Florida
city: Tampa
country: United States
facility: USF, Department of Psychiatry and Behavioral Neurosciences
state: Florida
city: West Palm Beach
country: United States
facility: Neuroscience Research Institute
state: Florida
city: Atlanta
country: United States
facility: Atlanta Behavioral Research, LLC
state: Georgia
city: Marietta
country: United States
facility: Psych Atlanta, P.C.
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: Chicago Research Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Joliet
country: United States
facility: Joliet Center for Clinical Research
state: Illinois
city: Lincolnwood
country: United States
facility: Pillar Clinical Research, LLC
state: Illinois
city: Skokie
country: United States
facility: Psychiatric Medicine Associates LLC
state: Illinois
city: Wichita
country: United States
facility: Ascension via Christi Research
state: Kansas
city: Wichita
country: United States
facility: University of Kansas School of Medicine
state: Kansas
city: Baltimore
country: United States
facility: Sheppard Pratt Health System
state: Maryland
city: Gaithersburg
country: United States
facility: CBH Health
state: Maryland
city: Boston
country: United States
facility: Copley Clinical
state: Massachusetts
city: Watertown
country: United States
facility: Adams Clinical
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Medical School
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Rochester Hills
country: United States
facility: Rochester Center for Behavioral Medicine (RCBM)
state: Michigan
city: Saint Charles
country: United States
facility: Midwest Research Group - St. Charles Psychiatric Associates
state: Missouri
city: New York
country: United States
facility: Clinilabs
state: New York
city: New York
country: United States
facility: The Medical Research Network, LLC
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Dayton
country: United States
facility: Midwest Clinical Research Center
state: Ohio
city: Oklahoma City
country: United States
facility: Paradigm Research Professionals, LLC
state: Oklahoma
city: Allentown
country: United States
facility: Lehigh Center for Clinical Research
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania Medical Center
state: Pennsylvania
city: Providence
country: United States
facility: The Warren Alpert Medical School of Brown University - Butler Hospital
state: Rhode Island
city: Austin
country: United States
facility: BioBehavioral Research of Austin PC
state: Texas
city: Dallas
country: United States
facility: Relaro Medical Trials
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Brain Health Consultants and TMS Center
state: Texas
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
city: Richardson
country: United States
facility: Pillar Clinical Research, LLC
state: Texas
city: The Woodlands
country: United States
facility: Family Psychiatry of The Woodlands
state: Texas
city: Wichita Falls
country: United States
facility: Grayline Research Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Center for Psychiatric Clinical Research
state: Virginia
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: