RECRUITING Phase 3 ClinicalTrials.gov

A Study of Esketamine Nasal Spray Versus Placebo Spray in Adult Participants With Treatment-resistant Depression

Sponsor: Janssen Research & Development, LLC • ClinicalTrials.gov ID: NCT07716098

Registry updated: 2026-09-25

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Description

The purpose of this study is to evaluate how well each individual dose of esketamine (56 milligrams \[mg\] and 84 mg) works when compared with placebo in improving depressive symptoms in participants with treatment resistant depression (individuals with major depressive disorder \[MDD\] who have not responded to at least 2 different antidepressant treatments given at an adequate dose for an adequate duration in the current episode of depression).

Interventions

Esketamine 56 mg (Drug)
Participants will self-administer 56 mg of esketamine as intranasal spray into each nostril.
Esketamine 84 mg (Drug)
Participants will self-administer 84 mg of esketamine as intranasal spray into each nostril.
Placebo (Drug)
Participants will self-administer placebo as intranasal spray into each nostril.

Eligibility criteria

Inclusion Criteria: * Participant must meet the diagnostic and statistical manual of mental disorders (5th edition) (DSM-5) diagnostic criteria for single-episode major depressive disorder (MDD) (if single episode MDD, the duration of the episode must be greater than or equal to \[\>=\] 12 months) or recurrent MDD, without psychotic features, based upon clinical assessment and confirmed by the mini international neuropsychiatric interview (MINI) as the primary diagnosis. Participant must have had the first onset of depression prior to 55 years of age * Participant must have had nonresponse (less than or equal to \[\<=\] 25 percent \[%\] improvement) to \>=2 oral antidepressant treatments in the current episode of depression, assessed using the massachusetts general hospital-antidepressant treatment response questionnaire (MGH-ATRQ), and confirmed by documented records (for example, medical/pharmacy/prescription records or a letter from a treating physician) * 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 versus trait, assessability, face validity, ecological validity, rule of three P's (SAFER) Interview * Participant must be comfortable with self-administration of nasal spray medication and be able to follow the nasal spray administration instructions provided * A female participant of childbearing potential must have a negative highly sensitive serum (β-human chorionic gonadotropin \[β-hCG\]) at the start of screening and a negative urine pregnancy test must be obtained before the first dose of study drug on Day 1, prior to randomization Exclusion Criteria: * The participant has used ketamine/esketamine (lifetime) * The participant's depressive symptoms have demonstrated nonresponse in the current major depressive episode to an adequate course of treatment with electroconvulsive therapy (ECT), defined as at least 7 treatments with unilateral/bilateral ECT, or to adequate course of treatment with transcranial magnetic stimulation (TMS), defined as at least 4 weeks of treatment with 5 sessions per week * Participant has received vagal nerve stimulation (VNS) or deep brain stimulation (DBS) in the current episode of depression * Participant has homicidal ideation/intent, per the investigator's clinical judgment, or has suicidal ideation with some intent to act within 6 months prior to the start of the screening phase, per the investigator's clinical judgment or based on the columbia suicide severity rating scale (C-SSRS), corresponding to a response of "Yes" on Item 4 (active suicidal ideation with some intent to act, without specific plan) or Item 5 (active suicidal ideation with specific plan and intent) for suicidal ideation on the C-SSRS, or a history of suicidal behavior within the past year prior to the start of the screening phase. Participants reporting suicidal ideation with intent to act or suicidal behavior prior to the start of the double-blind treatment phase should be excluded * Participant has a history of moderate or severe substance or alcohol use disorder according to DSM-5 criteria, except nicotine or caffeine, within 6 months before the start of the screening phase. a. A history (lifetime) of ketamine, phencyclidine (PCP), lysergic acid diethylamide (LSD), or 3, 4-methylenedioxy-methamphetamine (MDMA) hallucinogen-related use disorder is exclusionary * Participant has a current or history of seizures (uncomplicated childhood febrile seizures with no sequelae are not exclusionary)

Conditions

Depressive Disorder, Treatment-Resistant

Locations

Anderson Clinical Research — Redlands, California, United States
Artemis Institute for Clinical Research — San Diego, California, United States
Psych Atlanta, P.C. — Marietta, Georgia, United States
Psychiatric Medicine Associates LLC — Skokie, Illinois, United States
Neurobehavioral Research Inc — Cedarhurst, New York, United States
The Medical Research Network, LLC — New York, New York, United States
Northwest Clinical Research Center — Bellevue, Washington, United States
Kishiro Mental Clinic — Kawasaki, Japan
Tatsuta Clinic — Kobe, Japan
National Center of Neurology and Psychiatry — Kodaira-shi, Japan
Ichikawa Clinic — Maebashi, Japan
The Jikei University Hospital — Minatoku, Japan
Kyorin University Hospital — Mitaka, Japan
Arata Clinic — Nagasaki, Japan
Hokkaido University Hospital — Sapporo, Japan
Sangenjaya neurology-psychosomatic clinic — Setagaya Ku, Japan
Maynds Tower Mental Clinic — Shibuya-ku, Japan
Tottori University Hospital — Tottori, Japan
Chung Shan Medical University Hospital — Taichung, Taiwan
Taipei Medical University — Taipei, Taiwan
Taipei Veterans General Hospital — Taipei, Taiwan
Linkou Chang Gung Memorial Hospital — Taoyuan, Taiwan

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Official Source

Data sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

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