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Depressive Disorder, Treatment-ResistantPhase 4NCT04599855

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

A Phase 4 study testing Esketamine 56 mg and Esketamine 84 mg in people with Depressive Disorder, Treatment-Resistant, run by Janssen Research & Development, LLC at 54 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Depressive Disorder, Treatment-Resistant
What is being tested?
Esketamine 56 mg and Esketamine 84 mg
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
477 participants
Where
54 sitesUnited States
Study dates
4 Nov 2020to 31 Jan 2024
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

54 sites in 1 country.

54 sites in 1 country

United States54 sites

  • Lehigh Center for Clinical Research

    Allentown, Pennsylvania, 18104

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Atlanta Behavioral Research, LLC

    Atlanta, Georgia, 30338

  • BioBehavioral Research of Austin PC

    Austin, Texas, 78759

  • Sheppard Pratt Health System

    Baltimore, Maryland, 21204

  • UAB Department of Psychiatry and Behavioral Neurobiology

    Birmingham, Alabama, 35294

  • Copley Clinical

    Boston, Massachusetts, 02116

  • University of Virginia Center for Psychiatric Clinical Research

    Charlottesville, Virginia, 22903

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • Chicago Research Center

    Chicago, Illinois, 60634

  • University of Chicago

    Chicago, Illinois, 60637

  • Ohio State University

    Columbus, Ohio, 43210

  • Relaro Medical Trials

    Dallas, Texas, 75243

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75247

  • Midwest Clinical Research Center

    Dayton, Ohio, 45417

  • University of Connecticut Health Center

    Farmington, Connecticut, 06032

  • CBH Health

    Gaithersburg, Maryland, 20877

  • Behavioral Research Specialists LLC

    Glendale, California, 91206

  • Velocity Clinical Research, Hallandale Beach

    Hallandale, Florida, 33009

  • Brain Health Consultants and TMS Center

    Houston, Texas, 77046

  • The University of Texas Health Science Center at Houston

    Houston, Texas, 77054

  • UAB Huntsville Regional Medical Campus

    Huntsville, Alabama, 35801

  • Joliet Center for Clinical Research

    Joliet, Illinois, 60435

  • Accel Research Sites

    Lakeland, Florida, 33803

  • Pillar Clinical Research, LLC

    Lincolnwood, Illinois, 60712

  • Preferred Research Partners

    Little Rock, Arkansas, 72211

  • CalNeuro Research

    Los Angeles, California, 90025

  • Psych Atlanta, P.C.

    Marietta, Georgia, 30060

  • Clinilabs

    New York, New York, 10016

  • The Medical Research Network, LLC

    New York, New York, 10128

  • Pacific Research Partners

    Oakland, California, 94607

  • Paradigm Research Professionals, LLC

    Oklahoma City, Oklahoma, 73118

  • APG Research LLC

    Orlando, Florida, 32803

  • University of Pennsylvania Medical Center

    Philadelphia, Pennsylvania, 19104

  • The Warren Alpert Medical School of Brown University - Butler Hospital

    Providence, Rhode Island, 02906

  • Anderson Clinical Research

    Redlands, California, 92374

  • Pillar Clinical Research, LLC

    Richardson, Texas, 75080

  • Rochester Center for Behavioral Medicine (RCBM)

    Rochester Hills, Michigan, 48307

  • Midwest Research Group - St. Charles Psychiatric Associates

    Saint Charles, Missouri, 63304

  • University of California at San Diego

    San Diego, California, 92103-8620

  • Artemis Institute for Clinical Research

    San Diego, California, 92103

  • UCSF Nancy Friend Pritzker Psychiatry Building

    San Francisco, California, 94143

  • Velocity Clinical Research

    Santa Ana, California, 91704

  • CMB Clinical Trials

    Santee, California, 92071

  • Psychiatric Medicine Associates LLC

    Skokie, Illinois, 60076

  • Stony Brook University Medical Center

    Stony Brook, New York, 11794

  • USF, Department of Psychiatry and Behavioral Neurosciences

    Tampa, Florida, 33613

  • Family Psychiatry of The Woodlands

    The Woodlands, Texas, 77381

  • Adams Clinical

    Watertown, Massachusetts, 02472

  • Neuroscience Research Institute

    West Palm Beach, Florida, 33407

  • Ascension via Christi Research

    Wichita, Kansas, 67214

  • University of Kansas School of Medicine

    Wichita, Kansas, 67214

  • Grayline Research Center

    Wichita Falls, Texas, 76309

  • University of Massachusetts Medical School

    Worcester, Massachusetts, 01655

Other trials in United States

About this study

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

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).

Being tested
Esketamine 56 mg, Esketamine 84 mg, Placebo
Medical subject headings
Depressive Disorder, Treatment-Resistant

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Esketamine 56 mgDrug

    Also called JNJ-54135419

    Esketamine 56 mg will be self administered as nasal spray.

  • Esketamine 84 mgDrug

    Also called JNJ-54135419

    Esketamine 84 mg will be self administered as nasal spray.

  • PlaceboDrug

    Matching placebo will be self administered as nasal spray.

Study groups in NCT04599855
Study groupRoleWhat they receive
Esketamine 56 Milligram (mg)ExperimentalParticipants 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).
Receives: Drug: Esketamine 56 mg
Esketamine 84 mgExperimentalParticipants 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).
Receives: Drug: Esketamine 84 mg
PlaceboExperimentalParticipants 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).
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Double-blind Treatment Phase: Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Day 1 (Pre-randomization) to Day 28

    The MADRS was a clinician-rated scale designed to measure depression severity and detect changes due to antidepressant treatment. The scale consisted of 10 items, each of which was scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms). MADRS total score was the sum of scores from individual question items, which ranged from 0 to 60, higher scores represented a more severe condition. The MADRS evaluated apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, inability to feel (interest level), pessimistic thoughts, and suicidal thoughts. Negative change in MADRS total score indicated improvement.

    Measured: Day 1 (pre-randomization) to Day 28 (end of DB treatment phase)

Secondary outcomes (1)

  1. 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)

    The MADRS was a clinician-rated scale designed to measure depression severity and detect changes due to antidepressant treatment. The scale consisted of 10 items, each of which was scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms). MADRS total score was the sum of scores from individual question items, which ranged from 0 to 60, higher scores represented a more severe condition. The MADRS evaluated apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, inability to feel (interest level), pessimistic thoughts, and suicidal thoughts. Negative change in MADRS total score indicated improvement.

    Measured: Day 1 (pre-randomization) to Day 2 of DB treatment phase (24 hours post first dose on Day 1)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Oct 2020
  2. Study start4 Nov 2020
  3. Primary completion31 Jan 2024
  4. Study completion31 Jan 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
477 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04599855
Sponsor's protocol ID
CR108741
Other IDs
54135419TRD4005
Status last verified
Apr 2025
First submitted
21 Oct 2020
Last updated
25 Apr 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Janik A, Qiu X, Lane R, Popova V, Drevets WC, Canuso CM, Macaluso M, Mattingly GW, Shelton RC, Zajecka JM, Fu DJ. Esketamine Monotherapy in Adults With Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2025 Sep 1;82(9):877-887. doi: 10.1001/jamapsychiatry.2025.1317.

    PubMed 40601310

  • Vekhova KA, Namiot ED, Jonsson J, Schioth HB. Ketamine and Esketamine in Clinical Trials: FDA-Approved and Emerging Indications, Trial Trends With Putative Mechanistic Explanations. Clin Pharmacol Ther. 2025 Feb;117(2):374-386. doi: 10.1002/cpt.3478. Epub 2024 Oct 20.

    PubMed 39428602

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Esketamine 56 mg and Esketamine 84 mg in people with Depressive Disorder, Treatment-Resistant, run by Janssen Research & Development, LLC at 54 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 54 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Double-blind Treatment Phase: Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Day 1 (Pre-randomization) to Day 28 (time frame: Day 1 (pre-randomization) to Day 28 (end of DB treatment phase)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04599855, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Apr 2025; AzTrials last refreshed its copy on 7 Nov 2026.

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