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

Sponsor

Janssen Research & Development, LLC (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04599855

Collaborator

(none)

450

Enrollment

Locations

Arms

39.2

Anticipated Duration (Months)

6.9

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief 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).

Condition or Disease	Intervention/Treatment	Phase
Depressive Disorder, Treatment-Resistant	Drug: Esketamine 56 mg Drug: Esketamine 84 mg Drug: Placebo	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

450 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Nov 4, 2020

Anticipated Primary Completion Date :

Feb 9, 2024

Anticipated Study Completion Date :

Feb 9, 2024

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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) [Baseline to 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.

Secondary Outcome Measures

Change from Baseline in MADRS Total Score from Day 1 (Pre-randomization) to Day 2 [Baseline 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UAB Department of Psychiatry and Behavioral Neurobiology	Birmingham	Alabama	United States	35294
2	UAB Huntsville Regional Medical Campus	Huntsville	Alabama	United States	35801
3	Preferred Research Partners	Little Rock	Arkansas	United States	72211
4	Behavioral Research Specialists, LLC	Glendale	California	United States	91206
5	CalNeuro Research	Los Angeles	California	United States	90024
6	Pacific Research Partners	Oakland	California	United States	94607
7	Anderson Clinical Research	Redlands	California	United States	92374
8	University of California at San Diego	San Diego	California	United States	92103-8620
9	Artemis Institute for Clinical Research	San Diego	California	United States	92103
10	University of California San Francisco	San Francisco	California	United States	94143
11	Velocity Clinical Research	Santa Ana	California	United States	91704
12	CMB Clinical Trials	Santee	California	United States	92071
13	University of Connecticut Health Center	Farmington	Connecticut	United States	06032
14	Hartford Hospital - Institute of Living	Hartford	Connecticut	United States	06106
15	Yale University	New Haven	Connecticut	United States	06511
16	Velocity Clinical Research, Hallandale Beach	Hallandale Beach	Florida	United States	33009
17	Florida Research Center Inc.	Miami	Florida	United States	33174
18	APG Research, LLC	Orlando	Florida	United States	32803
19	USF, Department of Psychiatry and Behavioral Neurosciences	Tampa	Florida	United States	33613
20	Neuroscience Research Institute	West Palm Beach	Florida	United States	33407
21	Emory University Department of Psychiatry	Atlanta	Georgia	United States	30329
22	Atlanta Behavioral Research, LLC	Atlanta	Georgia	United States	30338
23	Psych Atlanta, P.C.	Marietta	Georgia	United States	30060
24	Rush University Medical Center	Chicago	Illinois	United States	60612
25	Chicago Research Center	Chicago	Illinois	United States	60634
26	University of Chicago	Chicago	Illinois	United States	60637
27	Mindful TMS	Hinsdale	Illinois	United States	60521
28	Joliet Center for Clinical Research	Joliet	Illinois	United States	60435
29	Pillar Clinical Research, LLC	Lincolnwood	Illinois	United States	60712
30	Psychiatric Medicine Associates LLC	Skokie	Illinois	United States	60076
31	Ascension via Christi Research	Wichita	Kansas	United States	67214
32	University of Kansas School of Medicine	Wichita	Kansas	United States	67214
33	Lake Charles Clinical Trials	Lake Charles	Louisiana	United States	70629
34	Sheppard Pratt Health System	Baltimore	Maryland	United States	21204
35	CBH Health	Gaithersburg	Maryland	United States	20877
36	Copley Clinical	Boston	Massachusetts	United States	02116
37	Adams Clinical	Watertown	Massachusetts	United States	02472
38	University of Massachusetts Medical School	Worcester	Massachusetts	United States	01655
39	University of Michigan	Ann Arbor	Michigan	United States	48109
40	Rochester Center for Behavioral Medicine (RCBM)	Rochester Hills	Michigan	United States	48307
41	Midwest Research Group - St. Charles Psychiatric Associates	Saint Charles	Missouri	United States	63304
42	Washington University School of Medicine	Saint Louis	Missouri	United States	63110-6311
43	Clinilabs	New York	New York	United States	10016
44	The Medical Research Network, LLC	New York	New York	United States	10128
45	Stony Brook University Medical Center	Stony Brook	New York	United States	11794
46	Clinical Trials of America	Hickory	North Carolina	United States	28601
47	Ohio State University	Columbus	Ohio	United States	43210
48	Midwest Clinical Research Center	Dayton	Ohio	United States	45417
49	Lindner Center of Hope	Mason	Ohio	United States	45040
50	Paradigm Research Professionals, LLC	Oklahoma City	Oklahoma	United States	73118
51	Lehigh Center for Clinical Research	Allentown	Pennsylvania	United States	18104
52	University of Pennsylvania Medical Center	Philadelphia	Pennsylvania	United States	19104
53	The Warren Alpert Medical School of Brown University - Butler Hospital	Providence	Rhode Island	United States	02906
54	Medical University of South Carolina	Charleston	South Carolina	United States	29425
55	BioBehavioral Research of Austin, PC	Austin	Texas	United States	78759
56	Future Search Trials of Dallas	Dallas	Texas	United States	75231
57	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75235
58	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75235
59	Relaro Medical Trials	Dallas	Texas	United States	75243
60	Brain Health Consultants and TMS Center	Houston	Texas	United States	77046
61	The University of Texas Health Science Center at Houston	Houston	Texas	United States	77054
62	Pillar Clinical Research, LLC	Richardson	Texas	United States	75080
63	Family Psychiatry of The Woodlands	The Woodlands	Texas	United States	77381
64	Grayline Research Center	Wichita Falls	Texas	United States	76309
65	University of Virginia Center for Psychiatric Clinical Research	Charlottesville	Virginia	United States	22903

Sponsors and Collaborators

Janssen Research & Development, LLC

Investigators

Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Janssen Research & Development, LLC

ClinicalTrials.gov Identifier:

NCT04599855

Other Study ID Numbers:

CR108741
54135419TRD4005

First Posted:

Oct 23, 2020

Last Update Posted:

Aug 18, 2022

Last Verified:

Aug 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Depressive Disorder

Depressive Disorder, Treatment-Resistant

Esketamine

Study Results

No Results Posted as of Aug 18, 2022