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

Janssen (J&J Innovative Medicine)

Status and phase: Enrolling; Phase 3

Conditions: Depressive Disorder, Treatment-Resistant

Treatments: Drug: Placebo; Drug: Esketamine 84 mg; Drug: Esketamine 56 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT07716098

54135419TRD3015

Details and patient eligibility

About

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).

Enrollment: 348 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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348 participants in 3 patient groups, including a placebo group

Esketamine 56 milligram (mg)

Experimental group

Description:

Participants will be randomized to receive double-blind (DB) treatment with esketamine 56 mg, twice a week for 4 weeks. Participants who complete the DB treatment phase on Day 28 may be eligible to participate in an open-label treatment phase and receive either esketamine 56 or 84 mg.

Treatment:

Drug: Esketamine 56 mg

Drug: Esketamine 84 mg

Esketamine 84 mg

Experimental group

Description:

Participants will be randomized to receive DB treatment with esketamine 84 mg, twice a week for 4 weeks. Participants who complete the DB treatment phase on Day 28 may be eligible to participate in an open-label treatment phase and receive either esketamine 56 or 84 mg.

Treatment:

Drug: Esketamine 56 mg

Drug: Esketamine 84 mg

Placebo

Placebo Comparator group

Description:

Participants will be randomized to receive DB treatment with placebo twice a week for 4 weeks. Participants who complete the DB treatment phase on Day 28 may be eligible to participate in an open-label treatment phase and receive either esketamine 56 mg or 84 mg.

Treatment:

Drug: Esketamine 56 mg

Drug: Esketamine 84 mg

Drug: Placebo