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

Depressive Disorder, Treatment-Resistant Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04599855
• Other study ID #: CR108741
• Secondary ID: 54135419TRD4005
• Status: Completed
• Phase: Phase 4
• Start date: November 4, 2020
• Est. completion date: January 31, 2024

Study information

• Verified date: March 2024
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 477
• Est. completion date: January 31, 2024
• Est. primary completion date: January 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Depressive Disorder
• Depressive Disorder, Treatment-Resistant

Intervention

Drug:
• Esketamine 56 mg
Esketamine 56 mg will be self administered as nasal spray.
• Esketamine 84 mg
Esketamine 84 mg will be self administered as nasal spray.
• Placebo
Matching placebo will be self administered as nasal spray.

Locations

Country	Name	City	State
United States	Lehigh Center for Clinical Research	Allentown	Pennsylvania
United States	University of Michigan	Ann Arbor	Michigan
United States	Atlanta Behavioral Research, LLC	Atlanta	Georgia
United States	BioBehavioral Research of Austin PC	Austin	Texas
United States	Sheppard Pratt Health System	Baltimore	Maryland
United States	UAB Department of Psychiatry and Behavioral Neurobiology	Birmingham	Alabama
United States	Copley Clinical	Boston	Massachusetts
United States	University of Virginia Center for Psychiatric Clinical Research	Charlottesville	Virginia
United States	Chicago Research Center	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	Ohio State University	Columbus	Ohio
United States	Relaro Medical Trials	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Midwest Clinical Research Center	Dayton	Ohio
United States	University of Connecticut Health Center	Farmington	Connecticut
United States	CBH Health	Gaithersburg	Maryland
United States	Behavioral Research Specialists LLC	Glendale	California
United States	Velocity Clinical Research, Hallandale Beach	Hallandale Beach	Florida
United States	Brain Health Consultants and TMS Center	Houston	Texas
United States	The University of Texas Health Science Center at Houston	Houston	Texas
United States	UAB Huntsville Regional Medical Campus	Huntsville	Alabama
United States	Joliet Center for Clinical Research	Joliet	Illinois
United States	Accel Research Sites	Lakeland	Florida
United States	Pillar Clinical Research, LLC	Lincolnwood	Illinois
United States	Preferred Research Partners	Little Rock	Arkansas
United States	CalNeuro Research	Los Angeles	California
United States	Psych Atlanta, P.C.	Marietta	Georgia
United States	Clinilabs	New York	New York
United States	The Medical Research Network, LLC	New York	New York
United States	Pacific Research Partners	Oakland	California
United States	Paradigm Research Professionals, LLC	Oklahoma City	Oklahoma
United States	APG Research LLC	Orlando	Florida
United States	University of Pennsylvania Medical Center	Philadelphia	Pennsylvania
United States	The Warren Alpert Medical School of Brown University - Butler Hospital	Providence	Rhode Island
United States	Anderson Clinical Research	Redlands	California
United States	Pillar Clinical Research, LLC	Richardson	Texas
United States	Rochester Center for Behavioral Medicine (RCBM)	Rochester Hills	Michigan
United States	Midwest Research Group - St. Charles Psychiatric Associates	Saint Charles	Missouri
United States	Artemis Institute for Clinical Research	San Diego	California
United States	University of California at San Diego	San Diego	California
United States	UCSF Nancy Friend Pritzker Psychiatry Building	San Francisco	California
United States	Velocity Clinical Research	Santa Ana	California
United States	CMB Clinical Trials	Santee	California
United States	Psychiatric Medicine Associates LLC	Skokie	Illinois
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	USF, Department of Psychiatry and Behavioral Neurosciences	Tampa	Florida
United States	Family Psychiatry of The Woodlands	The Woodlands	Texas
United States	Adams Clinical	Watertown	Massachusetts
United States	Neuroscience Research Institute	West Palm Beach	Florida
United States	Ascension via Christi Research	Wichita	Kansas
United States	University of Kansas School of Medicine	Wichita	Kansas
United States	Grayline Research Center	Wichita Falls	Texas
United States	University of Massachusetts Medical School	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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