Clinical trial NCT03097133: 54135419SUI3002: A Study to Evaluate the Efficacy and Safety 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 Adult Participants Assessed to be at Imminent Risk for Suicide
Official title: A Double-blind, Randomized, Placebo-controlled Study to Evaluate the Efficacy and Safety 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 Adult Subjects Assessed to be at Imminent Risk for Suicide
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Depressive Disorder, Major
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2017-03-31
Enrollment: 230
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy of intranasal esketamine 84 milligram (mg) compared with intranasal placebo in addition to comprehensive standard of care in reducing the symptoms of Major Depressive Disorder (MDD), including suicidal ideation, in participants who are assessed to be at imminent risk for suicide, as measured by the change from baseline on the Montgomery-Asberg Depression Rating Scale (MADRS) total score at 24 hours post first dose.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Participant must meet Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-5) diagnostic criteria for major depressive disorder (MDD), without psychotic features, based upon clinical assessment and confirmed by the Mini International Psychiatric Interview (MINI)
* Participants must have current suicidal ideation with intent, confirmed by a "Yes" response to Question B3 \[Think (even momentarily) about harming or of hurting or of injuring yourself: with at least some intent or awareness that you might die as a result; or think about suicide (ie, about killing yourself)?\] AND Question B10 \[Intend to act on thoughts of killing yourself?\] obtained from the MINI
* In the physician's opinion, acute psychiatric hospitalization is clinically warranted due to participant's imminent risk of suicide
* Participant has a Montgomery Asberg Depression Rating Scale (MADRS) total score of greater than (\>) 28 predose on Day 1
* As part of standard of care treatment, participant agrees to be hospitalized voluntarily for a recommended period of 14 days after randomization (may be shorter or longer if clinically warranted in the investigator's opinion) and take prescribed non-investigational antidepressant therapy(ies) for at least the duration of the double-blind treatment phase (Day 25)

Exclusion Criteria:

* Participant has a current DSM-5 diagnosis of bipolar (or related disorders), antisocial personality disorder, or obsessive compulsive disorder
* Participant currently meets DSM-5 criteria for borderline personality disorder. Note: Participant 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 clinical diagnosis of autism, dementia, or intellectual disability
* Participant has a current or prior DSM-5 diagnosis of a psychotic disorder, or MDD with psychotic features
* Participant meets the DSM-5 severity criteria for moderate or severe substance or alcohol use disorder, (except for nicotine or caffeine), within the 12 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 or current signs and symptoms of liver or renal insufficiency, clinically significant cardiac (including unstable coronary artery disease and congestive heart failure, tachyarrhythmias and recent myocardial infarction) or vascular, pulmonary, gastrointestinal, endocrine (including uncontrolled hyperthyroidism), neurologic (including current or past history of seizures except uncomplicated childhood febrile seizures with no sequelae), hematologic, rheumatologic, or metabolic (including severe dehydration/ hypovolemia) disease
* Participant has known allergies, hypersensitivity, intolerance or contraindications to esketamine or ketamine or its excipients

Primary outcomes:
measure: Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at 24 Hours Post First Dose (Last Observation Carried Forward [LOCF] Data): Double-blind (DB) Treatment Phase
timeFrame: Baseline (Day 1, predose) and 24 hours first post dose (Day 2)
measure: Change From Baseline in Clinical Global Impression-Severity of Suicidality - Revised (CGI-SS-R) Scale at 24 Hours Post First Dose (LOCF Data): DB Treatment Phase
timeFrame: Baseline (Day 1, predose) and 24 hours first post dose (Day 2)
Secondary outcomes:
measure: Number of Participants With Remission of Major Depressive Disorder (MADRS Total Score Less Than or Equal to [<=] 12): DB Treatment Phase
timeFrame: Days 1 (4 hours [h] postdose), 2, 4, 8, 11, 15, 18, 22 and 25 (predose and 4 hours postdose)
measure: Change From Baseline in MADRS Total Score at 4 Hours Post First Dose at Day 1 (4 Hours Post First Dose), and 2, 4, 8, 11, 15, 18, 22 and 25: DB Treatment Phase
timeFrame: Baseline (Day 1, predose), Days 1 (4 hours postdose), 2, 4, 8, 11, 15, 18, 22 and 25 (predose and 4 hours postdose)
measure: Change From Baseline in CGI-SS-R Score at 4 Hours Post First Dose at Day 1 (4 Hours Post First Dose), and 2, 4, 8, 11, 15, 18, 22 and 25: DB Treatment Phase
timeFrame: Baseline (Day 1, predose), Days 1 (4 hours postdose), 2, 4, 8, 11, 15, 18, 22 and 25
measure: Number of Participants Who Achieved Resolution of Suicidality (CGI-SS-R Score of 0 or 1): DB Treatment Phase
timeFrame: Days 1 (4 hours postdose), 2, 4, 8, 11, 15, 18, 22 and 25
measure: Change From Baseline in Clinical Global Impression of Imminent Suicide Risk (CGI-SR-I) at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25: DB Treatment Phase
timeFrame: Baseline (Day 1, predose), Days 1 (4 hours postdose), 2, 4, 8, 11, 15, 18, 22 and 25
measure: Change From Baseline in Beck Hopelessness Scale (BHS) Total Score at Days 8 and 25 in DB Treatment Phase
timeFrame: Baseline, Days 8 and 25
measure: Change From Baseline in European Quality of Life Group, 5-Dimension, 5-Level (EQ-5D-5L) Sum Score at Days 2, 11 and 25 of the DB Treatment Phase
timeFrame: Baseline, Days 2, 11 and 25
measure: Change From Baseline in European Quality of Life Group, Visual Analogue Scale (EQ-VAS) Score at Days 2, 11 and 25 of the DB Treatment Phase
timeFrame: Baseline, Days 2, 11 and 25
measure: Change From Baseline in EQ-5D-5L Health Status Index at Days 2, 11 and 25 of the DB Treatment Phase
timeFrame: Baseline, Days 2, 11 and 25
measure: Change From Baseline in Quality of Life in Depression Scale (QLDS) Total Score at Days 2, 11 and 25 of the DB Treatment Phase
timeFrame: Baseline, Days 2, 11 and 25
measure: Treatment Satisfaction Questionnaire for Medication (TSQM-9) Domain Score at Days 15 and 25: DB Treatment Phase
timeFrame: Days 15 and 25
measure: Change From Baseline in Suicide Ideation and Behavior Assessment Tool (SIBAT) Module 5 (My Risk) Question 3 (Participant-Reported Frequency of Suicidal Thinking) Score at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25: DB Treatment Phase
timeFrame: Baseline, Days 1 (4h postdose), 2, 4, 8, 11, 15, 18, 22 and 25
measure: Change From Baseline in Suicide Ideation and Behavior Assessment Tool (SIBAT) Module 7 (Clinician-rated Frequency of Suicidal Thinking [FoST]) Score at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25: DB Treatment Phase
timeFrame: Baseline, Days 1 (4 hours postdose), 2, 4, 8, 11, 15, 18, 22 and 25
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs): DB Treatment Phase
timeFrame: Up to Day 25
measure: Number of Participants With Treatment Emergent Abnormal Laboratory Values: DB Treatment Phase
timeFrame: Up to Day 25
measure: Number of Participants With Abnormal Nasal Examinations at Day 25: DB Treatment Phase
timeFrame: At Day 25
measure: Number of Participants With Treatment Emergent Abnormal Electrocardiogram (ECG) Values at Any Time: DB Treatment Phase
timeFrame: Up to Day 25
measure: Number of Participants With Abnormal Arterial Oxygen Saturation (SpO2) Levels (Less Than [<] 93%) as Assessed by Pulse Oximetry at Any Time: DB Treatment Phase
timeFrame: Up to Day 25
measure: Number of Participants With Treatment Emergent Vital Signs Abnormalities: DB Treatment Phase
timeFrame: Up to Day 25
measure: Number of Sedated Participants as Assessed by Modified Observer's Assessment of Alertness/Sedation (MOAA/S) Score at Any Time: DB Treatment Phase
timeFrame: Up to Day 25
measure: Number of Participants With an Increase in Clinician-administered Dissociative States Scale (CADSS) Total Score Over Time: DB Treatment Phase
timeFrame: Days 1, 4, 8, 11, 15, 18, 22 and 25
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California San Diego/Psychiatry
state: California
city: San Diego
country: United States
facility: Sharp Mesa Vista Hospital
state: California
city: Farmington
country: United States
facility: University of Conneticut School of Medicine
state: Connecticut
city: Miami
country: United States
facility: University of Miami Health System
state: Florida
city: North Miami
country: United States
facility: Innovative Clinical Research Inc
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Atlanta
country: United States
facility: Atlanta Behavioral Research, LLC
state: Georgia
city: Springfield
country: United States
facility: Memorial Medical Center
state: Illinois
city: Winfield
country: United States
facility: Neuroscience Research Institute
state: Illinois
city: Lake Charles
country: United States
facility: Lake Charles Clinical Trials
state: Louisiana
city: Baltimore
country: United States
facility: John Hopkins Hospital
state: Maryland
city: Las Vegas
country: United States
facility: Altea Research Institute
state: Nevada
city: Glen Oaks
country: United States
facility: The Zucker Hillside Hospital
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati, Dept of Psychiatry & Behavioral Neuroscience
state: Ohio
city: Johnson City
country: United States
facility: East Tennessee State University
state: Tennessee
city: Madison
country: United States
facility: University of Wisconsin Medical Center
state: Wisconsin
city: Banfield
country: Argentina
facility: Clínica Privada Banfield S.A
city: Ciudad de Buenos Aires
country: Argentina
facility: Hospital Fleni
city: Cordoba
country: Argentina
facility: Sanatorio Prof. Leon S. Morra
city: La Plata
country: Argentina
facility: Clinica Privada de Salud Mental Santa Teresa de Ávila
city: Vienna
country: Austria
facility: Medical University Vienna MUV
city: Wels
country: Austria
facility: Klinikum Wels Grieskirchen
city: Brugge
country: Belgium
facility: AZ Sint Jan Brugge Oostende AV
city: Gent
country: Belgium
facility: UZ Gent
city: Lede
country: Belgium
facility: ARIADNE
city: Belo Horizonte
country: Brazil
facility: Universidade Federal De Minas Gerais - Hospital das Clínicas
city: Fortaleza
country: Brazil
facility: Universidade Federal Do Ceara
city: Itapira
country: Brazil
facility: Instituto Bairral de Psiquiatria
city: Salvador
country: Brazil
facility: Hospital Universitario Professor Edgar Santos
city: Santo Andre
country: Brazil
facility: CEMEC - Centro Multidisciplinar de Estudos Clínicos
city: São Paulo
country: Brazil
facility: Hospital Das Clinicas Da Faculdade De Medicina Da USP
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Montréal
country: Canada
facility: Institut universitaire en sante mentale de Montreal
state: Quebec
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
city: Havirov
country: Czechia
facility: Nemocnice s pol. Havirov, p.o.
city: Klecany
country: Czechia
facility: Narodni ustav dusevniho zdravi
city: Praha
country: Czechia
facility: Vseobecna Fakultní Nemocnice
city: Praha
country: Czechia
facility: Ústrední vojenské nemocnice Praha
city: Bohars
country: France
facility: Hôpital de Bohars
city: Montpellier
country: France
facility: CHRU Montpellier Hopital Lapeyronie
city: Nimes
country: France
facility: CHU Caremeau
city: Paris
country: France
facility: Hopital Sainte Anne
city: Saint-Priest en Jarez
country: France
facility: CHU Saint Etienne Hopital Nord
city: Toulouse
country: France
facility: CHU Toulouse
city: Kaunas County
country: Lithuania
facility: Republic Kaunas Hospital
city: Kaunas
country: Lithuania
facility: Hospital of Lithuanian University of Health Sciences Kaunas Clinics
city: Vilnius
country: Lithuania
facility: Vilnius Mental Health Center
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Gorlice
country: Poland
facility: Szpital Specjalistyczny im H Klimontowicza Oddzial Psychiatryczny
city: Lodz
country: Poland
facility: SPZOZ CSK UM w Lodzi Klinika Zaburzen Afektywnych i Psychotycznych
city: Pruszkow
country: Poland
facility: Klinika Psychiatryczna WUM Mazowieckie Specjalistyczne Centrum Zdrowia im prof Jana Mazurkiewicza
city: Barcelona
country: Spain
facility: Hosp Univ Vall D Hebron
city: Barcelona
country: Spain
facility: Inst. Internac. Neurociencias Aplicadas
city: Bilbao
country: Spain
facility: Hosp. Univ. de Basurto
city: Pamplona
country: Spain
facility: Clinica Univ. de Navarra
city: Bursa
country: Turkey
facility: Bursa Sevket Yilmaz Research and Training Hospital
city: Bursa
country: Turkey
facility: Uludag University Medical Faculty
city: Istanbul
country: Turkey
facility: Sisli Etfal Research Training Hospital
city: Samsun
country: Turkey
facility: Samsun Psychiatric Hospital
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Rozjabek H, Li N, Hartmann H, Fu DJ, Canuso C, Jamieson C. Assessing the meaningful change threshold of Quality of Life in Depression Scale using data from two phase 3 studies of esketamine nasal spray. J Patient Rep Outcomes. 2022 Jul 10;6(1):74. doi: 10.1186/s41687-022-00453-y.
citation: Dean RL, Hurducas C, Hawton K, Spyridi S, Cowen PJ, Hollingsworth S, Marquardt T, Barnes A, Smith R, McShane R, Turner EH, Cipriani A. Ketamine and other glutamate receptor modulators for depression in adults with unipolar major depressive disorder. Cochrane Database Syst Rev. 2021 Sep 12;9(9):CD011612. doi: 10.1002/14651858.CD011612.pub3.
citation: Ionescu DF, Fu DJ, Qiu X, Lane R, Lim P, Kasper S, Hough D, Drevets WC, Manji H, Canuso CM. Esketamine Nasal Spray for Rapid Reduction of Depressive Symptoms in Patients With Major Depressive Disorder Who Have Active Suicide Ideation With Intent: Results of a Phase 3, Double-Blind, Randomized Study (ASPIRE II). Int J Neuropsychopharmacol. 2021 Jan 20;24(1):22-31. doi: 10.1093/ijnp/pyaa068.