Study to Evaluate the Efficacy and Safety of 3 Fixed Doses of Intranasal Esketamine in Addition to Comprehensive Standard of Care for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicidal Ideation, in Pediatric Participants Assessed to be at Imminent Risk for Suicide

Sponsor

Janssen Research & Development, LLC (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03185819

Collaborator

(none)

146

Enrollment

Locations

Arms

66.7

Anticipated Duration (Months)

2.2

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the efficacy of a single (first) dose of 3 fixed doses of intranasal esketamine {28 milligram (mg), 56 mg, and 84 mg} compared with psychoactive placebo (oral midazolam) in rapidly reducing the symptoms of major depressive disorder (MDD) including suicidal ideation in participants 12 to less than 18 years of age who are assessed to be at imminent risk for suicide.

Condition or Disease	Intervention/Treatment	Phase
Depressive Disorder, Major	Drug: Intranasal Placebo Drug: Midazolam Placebo Solution Drug: Midazolam Drug: Esketamine Drug: Esketamine Drug: Esketamine	Phase 2

Detailed Description

This study will enroll participants with major depressive disorder (MDD) presenting with suicidal ideation who are assessed to be at imminent risk for suicide. The study will be conducted in 4 phases: a screening evaluation performed within 48 hours prior to Day 1 intranasal dose; a 25-day double-blind treatment phase (Days 1-25); an 8-week initial post-treatment phase (Days 25-81); and a subsequent phase to complete a full 6-month post-treatment follow-up (Days 81-200). Efficacy, safety, pharmacokinetic, biomarker, and pharmacogenomic evaluations will be performed in the study at defined schedule. The duration of the participant's participation will be approximately 29 weeks. If you or a loved one are having thoughts of suicide, please seek immediate medical help. Go to the emergency room or call the National Suicide Prevention Lifeline at 1-800-273-8255.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

146 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Double-blind, Randomized, Psychoactive Placebo-controlled, Study to Evaluate the Efficacy and Safety of 3 Fixed Doses (28 mg, 56 mg and 84 mg) of Intranasal Esketamine in Addition to Comprehensive Standard of Care for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicidal Ideation, in Pediatric Subjects Assessed to be at Imminent Risk for Suicide

Actual Study Start Date :

Oct 5, 2017

Anticipated Primary Completion Date :

Apr 27, 2023

Anticipated Study Completion Date :

Apr 27, 2023

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Oral Midazolam + Intranasal Placebo Participants will receive midazolam solution 0.125 milligram per kilogram (mg/kg) orally 2 times per week for 4 weeks and 3 intranasal doses of matched placebo to esketamine.	Drug: Intranasal Placebo Participants will receive placebo as intranasal dose to match intranasal esketamine. Drug: Midazolam Participants will receive midazolam solution 0.125 mg/kg as oral dose to match placebo.
Experimental: Oral Placebo + Esketamine 84 mg Participants will receive intranasal esketamine 84 mg as 3 intranasal doses of esketamine in each nostril (each dose contains 14 mg of esketamine) along with oral placebo 2 times per week for 4 weeks.	Drug: Midazolam Placebo Solution Participants will receive placebo as oral dose to match midazolam drug. Drug: Esketamine Participants will receive esketamine at a dose of 84 mg as intranasal solution.
Experimental: Oral Placebo + Esketamine 56 mg Participants will receive intranasal esketamine 56 mg as 2 intranasal doses of esketamine in each nostril (each dose contains 14 mg of esketamine) along with oral placebo 2 times per week for 4 weeks.	Drug: Midazolam Placebo Solution Participants will receive placebo as oral dose to match midazolam drug. Drug: Esketamine Participants will receive esketamine at a dose of 56 mg as intranasal solution.
Experimental: Oral Placebo + Esketamine 28 mg Participants will receive intranasal esketamine 28 mg as 1 intranasal doses of esketamine in each nostril (each dose contains 14 mg of esketamine) along with oral placebo 2 times per week for 4 weeks.	Drug: Midazolam Placebo Solution Participants will receive placebo as oral dose to match midazolam drug. Drug: Esketamine Participants will receive esketamine at a dose of 28 mg as intranasal solution.

Outcome Measures

Primary Outcome Measures

Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at 24 Hours Post First Dose [Baseline and 24 hours post-administration of first dose on Day 1]
The CDRS-R has been widely used for the evaluation of children and adolescents with major depressive disorder (MDD). The CDRS-R total score is the sum of the responses to 17 questions. Each question is graded on a 5- or 7-point scale. The highest possible score is 113 (the most severe measure of depression), and the lowest is 17 (not suffering from depression).

Eligibility Criteria

Criteria

Ages Eligible for Study:

9 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Participants must meet diagnostic and statistical manual of mental disorders (5th edition) diagnostic criteria for major depressive disorder (MDD), without psychotic features, based upon clinical assessment and confirmed by the mini international neuropsychiatric interview for children and adolescents (MINI KID)
Participant must have a children's depression rating scale-revised (CDRS-R) total score of equal or more than (>=) 58 predose on Day 1
As part of standard of care treatment, participant must agree to be hospitalized voluntarily for a recommended period of 5 days after randomization (may be shorter or longer if clinically warranted in the investigator's opinion)
As part of the newly initiated or optimized standard of care treatment, participant must agree to take one of the prescribed non-investigational antidepressant medications (fluoxetine, escitalopram, sertraline; and 9-11 years old participants at US-sites only: fluoxetin [preferred], sertraline) at least during the double-blind treatment phase (Day 25)
As part of standard of care treatment, participant must agree to participate in a specific psychological intervention (individual cognitive behavioral therapy [CBT], interpersonal therapy, family therapy or psychodynamic psychotherapy) at least through the initial 8-week post-treatment follow-up period (Day 81)

Exclusion Criteria:

Participants has a current DSM-5 diagnosis of bipolar (or related disorders), intellectual disability, autism spectrum disorder, conduct disorder, anorexia nervosa, oppositional defiant disorder, or obsessive compulsive disorder
Participants currently meets DSM-5 criteria for borderline personality disorder. Participants not meeting full DSM-5 criteria for borderline personality disorder but exhibiting recurrent suicidal gestures, threats, or self-mutilating behaviors should also be excluded
Participant has a current or prior DSM-5 diagnosis of a psychotic disorder or MDD with psychosis
Participant meets the DSM-5 severity criteria for moderate or severe substance or alcohol use disorder (except for nicotine or caffeine) within the 6 months before screening. 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 history of seizure disorder

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Asclepes Research	Panorama City	California	United States	91402
2	Rady Children's Hospital	San Diego	California	United States	92123
3	University of California, San Francisco	San Francisco	California	United States	94143
4	Institute of Living/ Hartford Hospital	Hartford	Connecticut	United States	06106
5	Yale University	New Haven	Connecticut	United States	06520
6	Atlanta Center for Medical Research	Atlanta	Georgia	United States	30331
7	Atlanta Behavioral Research, LLC	Atlanta	Georgia	United States	30338
8	Rush University Medical Center	Chicago	Illinois	United States	60612
9	SIU School of Medicine	Springfield	Illinois	United States	62703
10	Neuroscience Research Institute	Winfield	Illinois	United States	60190
11	Riley Hospital for Children at Indiana University Health	Indianapolis	Indiana	United States	46202
12	Beacon Medical Group Clinical Research	South Bend	Indiana	United States	46617
13	University of Iowa, Carver College of Medicine	Iowa City	Iowa	United States	52242
14	Lake Charles Clinical Trials	Lake Charles	Louisiana	United States	70629
15	Sheppard Pratt Health System	Baltimore	Maryland	United States	21204
16	Johns Hopkins Hospital, Child and Adolescent Psychiatry	Baltimore	Maryland	United States	21224
17	CBH Health	Gaithersburg	Maryland	United States	20877
18	State University of New York at Buffalo	Buffalo	New York	United States	14215
19	Columbia University Medical Center	New York	New York	United States	10032
20	University North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599
21	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina	United States	27103
22	University of Cincinnati Hospital	Cincinnati	Ohio	United States	45219
23	University Hospital of Cleveland	Cleveland	Ohio	United States	44106
24	Ohio State University	Columbus	Ohio	United States	43210
25	Tennessee State University	Johnson City	Tennessee	United States	37614
26	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37212
27	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390-9063
28	Hopital Erasme	Brussels		Belgium	1070
29	Hospital Universitario Professor Edgar Santos	Bahia		Brazil	40110-060
30	Trial Tech Tecnologia em Pesquisas com Medicamentos	Curitiba		Brazil	80240-280
31	Hospital Infantil Pequeno Príncipe - Associação Hospitalar de Proteção à Infância Dr. Raul Carneiro	Curitiba		Brazil	80250-060
32	Bioserv SMO - HSVP ( Hospital São Vicente de Paulo)	Passo Fundo		Brazil	99010-080
33	Hospital de Clínicas de Porto Alegre/ HCPA / UFRGS	Porto Alegre		Brazil	90035-003
34	CEMEC - Centro Multidisciplinar de Estudos Clínicos	São Bernardo do Campo		Brazil	09715-090
35	Hospital São Sebastião	Turvo		Brazil	88930-000
36	Mental Health Center - Rousse	Ruse		Bulgaria	7003
37	Multiprofile Hospital for Active Treatment - MHAT Sveta Marina EAD	Varna		Bulgaria
38	Hospices Civils de Lyon HCL	Bron		France	69677
39	CHRU Lille - Hôpital Fontan 1	Lille		France	59000
40	CHU Nantes	Nantes		France	44093
41	Hôpital Universitaire Pitié-Salpêtrière	Paris		France	75013
42	Hopital Sainte Anne	Paris		France	75014
43	Hôpital Robert Debré	Paris		France	75019
44	CHU Saint-etienne	Saint-Priest-En-Jarez		France	42270
45	Vadaskert Gyermek- és Ifjúságpszichiátriai Kórház és Szakambulancia	Budapest		Hungary
46	Szegedi Tudomanyegyetem	Szeged		Hungary
47	Azienda Ospedaliera G. Brotzu	Cagliari		Italy	09134
48	OSP RIUNITI-DIP Donna- Bambino	Foggia		Italy	71122
49	Ospedale di Merano	Merano		Italy	39012
50	Azienda Ospedaliera Universitaria Policlinico G. Martino	Messina		Italy	98125
51	Azienda Ospedaliera Universitaria Federico II	Napoli		Italy	80138
52	IRCCS C. Mondino, Istituto Neurologico Nazionale, Fondazione	Pavia		Italy	27100
53	Ospedale Pediatrico Bambin Gesù	Roma		Italy	00165
54	Irccs Burlo-Garofalo	Trieste		Italy	34137
55	Klinika Psychiatrii Dzieci i Mlodziezy, CM UJ	Krakow		Poland	31-501
56	Dzieciecy Szpital Kliniczny im. Jozefa Polikarpa Brudzinskiego	Warszawa		Poland	02-091
57	Instytut Psychiatrii i Neurologii Klinika Psychiatrii Dzieci i Mlodziezy	Warszawa		Poland	02-957
58	Wojewódzki Szpital Specjalistyczny im. J. Gromkowskiego, Oddział Psychiatryczny Dzieci i Młodzieży	Wroclaw		Poland	51-149
59	Hosp. Clinic I Provincial de Barcelona	Barcelona		Spain	08036
60	Hosp. Sant Joan de Deu	Esplugues de Llobregat		Spain	08950
61	Hosp. Gral. Univ. Gregorio Marañon	Madrid		Spain	28007
62	Hosp. Infantil Univ. Niño Jesus	Madrid		Spain	28009
63	Hosp. Univ. Pta. de Hierro Majadahonda	Majadahonda		Spain	28222
64	Hosp. Univ. Central de Asturias	Oviedo		Spain	33011
65	Clinica Univ. de Navarra	Pamplona		Spain	31008
66	Corporacio Sanitari Parc Tauli	Sabadell		Spain	08208