A Study of Esketamine Nasal Spray, Administered as Monotherapy, in Adult Participants With Treatment-resistant Depression

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

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).

Study Overview

• Status: Completed
• Conditions: Depressive Disorder, Treatment-Resistant
• Intervention / Treatment: Drug: Esketamine 56 mg; Drug: Esketamine 84 mg; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 477
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Study Contact; Phone Number: 844-434-4210; Email: Participate-In-This-Study@its.jnj.com

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • UAB Department of Psychiatry and Behavioral Neurobiology
    • Huntsville, Alabama, United States, 35801
      • UAB Huntsville Regional Medical Campus
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Preferred Research Partners
  • California
    • Glendale, California, United States, 91206
      • Behavioral Research Specialists LLC
    • Los Angeles, California, United States, 90025
      • CalNeuro Research
    • Oakland, California, United States, 94607
      • Pacific Research Partners
    • Redlands, California, United States, 92374
      • Anderson Clinical Research
    • San Diego, California, United States, 92103
      • Artemis Institute for Clinical Research
    • San Diego, California, United States, 92103-8620
      • University of California at San Diego
    • San Francisco, California, United States, 94143
      • UCSF Nancy Friend Pritzker Psychiatry Building
    • Santa Ana, California, United States, 91704
      • Velocity Clinical Research
    • Santee, California, United States, 92071
      • CMB Clinical Trials
  • Connecticut
    • Farmington, Connecticut, United States, 06032
      • University of Connecticut Health Center
  • Florida
    • Hallandale Beach, Florida, United States, 33009
      • Velocity Clinical Research, Hallandale Beach
    • Lakeland, Florida, United States, 33803
      • Accel Research Sites
    • Orlando, Florida, United States, 32803
      • APG Research LLC
    • Tampa, Florida, United States, 33613
      • USF, Department of Psychiatry and Behavioral Neurosciences
    • West Palm Beach, Florida, United States, 33407
      • Neuroscience Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30338
      • Atlanta Behavioral Research, LLC
    • Marietta, Georgia, United States, 30060
      • Psych Atlanta, P.C.
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Chicago, Illinois, United States, 60634
      • Chicago Research Center
    • Joliet, Illinois, United States, 60435
      • Joliet Center for Clinical Research
    • Lincolnwood, Illinois, United States, 60712
      • Pillar Clinical Research, LLC
    • Skokie, Illinois, United States, 60076
      • Psychiatric Medicine Associates LLC
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Ascension Via Christi Research
    • Wichita, Kansas, United States, 67214
      • University of Kansas School of Medicine
  • Maryland
    • Baltimore, Maryland, United States, 21204
      • Sheppard Pratt Health System
    • Gaithersburg, Maryland, United States, 20877
      • CBH Health
  • Massachusetts
    • Boston, Massachusetts, United States, 02116
      • Copley Clinical
    • Watertown, Massachusetts, United States, 02472
      • Adams Clinical
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Medical School
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Rochester Hills, Michigan, United States, 48307
      • Rochester Center for Behavioral Medicine (RCBM)
  • Missouri
    • Saint Charles, Missouri, United States, 63304
      • Midwest Research Group - St. Charles Psychiatric Associates
  • New York
    • New York, New York, United States, 10128
      • The Medical Research Network, LLC
    • New York, New York, United States, 10016
      • Clinilabs
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University
    • Dayton, Ohio, United States, 45417
      • Midwest Clinical Research Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73118
      • Paradigm Research Professionals, LLC
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18104
      • Lehigh Center for Clinical Research
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Medical Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • The Warren Alpert Medical School of Brown University - Butler Hospital
  • Texas
    • Austin, Texas, United States, 78759
      • BioBehavioral Research of Austin PC
    • Dallas, Texas, United States, 75243
      • Relaro Medical Trials
    • Dallas, Texas, United States, 75247
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77054
      • The University of Texas Health Science Center at Houston
    • Houston, Texas, United States, 77046
      • Brain Health Consultants and TMS Center
    • Richardson, Texas, United States, 75080
      • Pillar Clinical Research, LLC
    • The Woodlands, Texas, United States, 77381
      • Family Psychiatry of The Woodlands
    • Wichita Falls, Texas, United States, 76309
      • Grayline Research Center
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Center for Psychiatric Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Esketamine 56 Milligram (mg); Participants will receive nasal spray treatment with esketamine 56 mg twice a week for 4 weeks. Participants may participate in an open-label treatment/observation phase, following completion of the double-blind treatment phase assessments (which includes the Day 28 Montgomery-Asberg Depression Rating Scale [MADRS] assessment).	Drug: Esketamine 56 mg; Esketamine 56 mg will be self administered as nasal spray.; Other Names: JNJ-54135419
Experimental: Esketamine 84 mg; Participants will receive nasal spray treatment with esketamine 84 mg twice a week for 4 weeks. Participants may participate in an open-label treatment/observation phase, following completion of the double-blind treatment phase assessments (which includes the Day 28 MADRS assessment).	Drug: Esketamine 84 mg; Esketamine 84 mg will be self administered as nasal spray.; Other Names: JNJ-54135419
Experimental: Placebo; Participants will receive nasal spray treatment with placebo twice a week for 4 weeks. Participants may participate in an open-label treatment/observation phase, following completion of the double-blind treatment phase assessments (which includes the Day 28 MADRS assessment).	Drug: Placebo; Matching placebo will be self administered as nasal spray.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score from Day 1 (Pre-randomization) to the End of the 4-week Double-Blind Treatment Phase (Day 28)	MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The scale 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 possible score of 60. Higher scores represent a more severe condition.	Baseline to Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in MADRS Total Score from Day 1 (Pre-randomization) to Day 2	MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The scale 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 possible score of 60. Higher scores represent a more severe condition.	Baseline to Day 2

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2020
• Primary Completion (Actual): January 31, 2024
• Study Completion (Actual): January 31, 2024

Study Registration Dates

• First Submitted: October 21, 2020
• First Submitted That Met QC Criteria: October 21, 2020
• First Posted (Actual): October 23, 2020

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Treatment-Resistant; Psychotropic Drugs; Antidepressive Agents; Esketamine
• Other Study ID Numbers: CR108741; 54135419TRD4005 (Other Identifier: Janssen Research & Development, LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No