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

NCT03097133 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: CR1082852016-003992-2354135419SUI3002
• Study Type: interventional
• Target: 230
• Locations: 12 countries
• Sites: 61

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.

Conditions

Depressive Disorder, Major

Outcome Measures

Primary Outcomes (2)

• 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

  MADRS is clinician-rated scale designed to be used in participants with Major Depressive Disorder (MDD) to measure depression severity and detect changes due to antidepressant treatment. It evaluates apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic and suicidal thoughts. Scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms), summed for total possible score of 0 to 60. Higher scores represent more severe condition. Negative change in score indicates improvement.

  Baseline (Day 1, predose) and 24 hours first post dose (Day 2)

• 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

  Clinical global impression-severity of suicidality-revised (CGI-SS-R) scale is revised version of the clinical global impression severity scale (CGI-S),a global rating scale that gives an overall measure of the severity of a participants illness. The CGI-SS-R summarizes the clinician's overall impression of severity of suicidality on a 7-point scale from 0 (normal, not at all suicidal) to 6 (among the most extremely suicidal participants), based on the totality of information available to the clinician. Higher score indicates a more severe condition. Negative change in score indicates improvement.

  Baseline (Day 1, predose) and 24 hours first post dose (Day 2)

Secondary Outcomes (21)

• Number of Participants With Remission of Major Depressive Disorder (MADRS Total Score Less Than or Equal to [<=] 12): DB Treatment Phase

  Days 1 (4 hours [h] postdose), 2, 4, 8, 11, 15, 18, 22 and 25 (predose and 4 hours postdose)

• 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

  Baseline (Day 1, predose), Days 1 (4 hours postdose), 2, 4, 8, 11, 15, 18, 22 and 25 (predose and 4 hours postdose)

• 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

  Baseline (Day 1, predose), Days 1 (4 hours postdose), 2, 4, 8, 11, 15, 18, 22 and 25

• Number of Participants Who Achieved Resolution of Suicidality (CGI-SS-R Score of 0 or 1): DB Treatment Phase

  Days 1 (4 hours postdose), 2, 4, 8, 11, 15, 18, 22 and 25

• 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

  Baseline (Day 1, predose), Days 1 (4 hours postdose), 2, 4, 8, 11, 15, 18, 22 and 25

Study Arms (2)

Esketamine + Standard of care

EXPERIMENTAL

Participants will receive intranasal esketamine 84 milligram (mg) on Day 1, 4, 8, 11, 15, 18, 22, and 25 along with standard of care antidepressant treatment.

Drug: Esketamine; Other: Standard of Care

Placebo + Standard of care

PLACEBO COMPARATOR

Participants will receive intranasal placebo on Day 1, 4, 8, 11, 15, 18, 22, and 25 along with standard of care antidepressant treatment.

Drug: Placebo; Other: Standard of Care

Interventions

Esketamine DRUG

Participants will receive intranasal esketamine 84 milligram (mg) two times per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25).

Esketamine + Standard of care

Placebo DRUG

Participants will receive intranasal placebo two times per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25).

Placebo + Standard of care

Standard of Care OTHER

The standard of care antidepressant treatment (antidepressant monotherapy or antidepressant plus augmentation therapy) will be determined by the treating physician(s) based on clinical judgement and practice guidelines prior to randomization, and the treatment will be initiated on Day 1.

Esketamine + Standard of care; Placebo + Standard of care

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (61)

University of California San Diego/Psychiatry

San Diego, California, 92103-8229, United States

Location

Sharp Mesa Vista Hospital

San Diego, California, 92123, United States

Location

University of Conneticut School of Medicine

Farmington, Connecticut, 06030, United States

Location

University of Miami Health System

Miami, Florida, 33136, United States

Location

Innovative Clinical Research Inc

North Miami, Florida, 33161, United States

Location

University of South Florida

Tampa, Florida, 33613, United States

Location

Atlanta Behavioral Research, LLC

Atlanta, Georgia, 30338, United States

Location

Memorial Medical Center

Springfield, Illinois, 62702, United States

Location

Neuroscience Research Institute

Winfield, Illinois, 60190, United States

Location

Lake Charles Clinical Trials

Lake Charles, Louisiana, 70629, United States

Location

John Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Altea Research Institute

Las Vegas, Nevada, 89102, United States

Location

The Zucker Hillside Hospital

Glen Oaks, New York, 11004, United States

Location

Stony Brook University Medical Center

Stony Brook, New York, 11794, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

University of Cincinnati, Dept of Psychiatry & Behavioral Neuroscience

Cincinnati, Ohio, 45219, United States

Location

East Tennessee State University

Johnson City, Tennessee, 37604, United States

Location

University of Wisconsin Medical Center

Madison, Wisconsin, 53705, United States

Location

Clínica Privada Banfield S.A

Banfield, B1828CKR, Argentina

Location

Hospital Fleni

Ciudad de Buenos Aires, C1428AQK, Argentina

Location

Sanatorio Prof. Leon S. Morra

Córdoba, X5009BIN, Argentina

Location

Clinica Privada de Salud Mental Santa Teresa de Ávila

La Plata, B1904ADM, Argentina

Location

Medical University Vienna MUV

Vienna, 1090, Austria

Location

Klinikum Wels Grieskirchen

Wels, 4600, Austria

Location

AZ Sint Jan Brugge Oostende AV

Bruges, 8000, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

ARIADNE

Lede, 9340, Belgium

Location

Universidade Federal De Minas Gerais - Hospital das Clínicas

Belo Horizonte, 30130-100, Brazil

Location

Universidade Federal Do Ceara

Fortaleza, 60430-370, Brazil

Location

Instituto Bairral de Psiquiatria

Itapira, 13970-905, Brazil

Location

Hospital Universitario Professor Edgar Santos

Salvador, 40110-060, Brazil

Location

CEMEC - Centro Multidisciplinar de Estudos Clínicos

Santo André, 09190-510, Brazil

Location

Hospital Das Clinicas Da Faculdade De Medicina Da USP

São Paulo, 05403-903, Brazil

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Institut universitaire en sante mentale de Montreal

Montreal, Quebec, H1N 3M5, Canada

Location

Fakultni nemocnice Brno

Brno, 62500, Czechia

Location

Nemocnice s pol. Havirov, p.o.

Havířov, 73601, Czechia

Location

Narodni ustav dusevniho zdravi

Klecany, 25067, Czechia

Location

Vseobecna Fakultní Nemocnice

Prague, 12000, Czechia

Location

Ústrední vojenské nemocnice Praha

Prague, 16902, Czechia

Location

Hôpital de Bohars

Bohars, 29820, France

Location

CHRU Montpellier Hopital Lapeyronie

Montpellier, 34090, France

Location

CHU Caremeau

Nîmes, 30029, France

Location

Hopital Sainte Anne

Paris, 75014, France

Location

CHU Saint Etienne Hopital Nord

Saint-Priest-en-Jarez, 42270, France

Location

CHU Toulouse

Toulouse, 31059, France

Location

Hospital of Lithuanian University of Health Sciences Kaunas Clinics

Kaunas, LT-50009, Lithuania

Location

Republic Kaunas Hospital

Kaunas County, Lithuania

Location

Vilnius Mental Health Center

Vilnius, 10309, Lithuania

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80 124, Poland

Location

Szpital Specjalistyczny im H Klimontowicza Oddzial Psychiatryczny

Gorlice, 38-300, Poland

Location

SPZOZ CSK UM w Lodzi Klinika Zaburzen Afektywnych i Psychotycznych

Lodz, 92-216, Poland

Location

Klinika Psychiatryczna WUM Mazowieckie Specjalistyczne Centrum Zdrowia im prof Jana Mazurkiewicza

Pruszków, 05 802, Poland

Location

Hosp Univ Vall D Hebron

Barcelona, 08035, Spain

Location

Inst. Internac. Neurociencias Aplicadas

Barcelona, 8006, Spain

Location

Hosp. Univ. de Basurto

Bilbao, 48013, Spain

Location

Clinica Univ. de Navarra

Pamplona, 31008, Spain

Location

Bursa Sevket Yilmaz Research and Training Hospital

Bursa, 16240, Turkey (Türkiye)

Location

Uludag University Medical Faculty

Bursa, 16285, Turkey (Türkiye)

Location

Sisli Etfal Research Training Hospital

Istanbul, 34360, Turkey (Türkiye)

Location

Samsun Psychiatric Hospital

Samsun, 55070, Turkey (Türkiye)

Location

Related Publications (6)

• Fu DJ, Zhang Q, Shi L, Borentain S, Guo S, Mathews M, Anjo J, Nash AI, O'Hara M, Canuso CM. Esketamine versus placebo on time to remission in major depressive disorder with acute suicidality. BMC Psychiatry. 2023 Aug 11;23(1):587. doi: 10.1186/s12888-023-05017-y.

  PMID: 37568081 DERIVED

• Jamieson C, Canuso CM, Ionescu DF, Lane R, Qiu X, Rozjabek H, Molero P, Fu DJ. Effects of esketamine on patient-reported outcomes in major depressive disorder with active suicidal ideation and intent: a pooled analysis of two randomized phase 3 trials (ASPIRE I and ASPIRE II). Qual Life Res. 2023 Nov;32(11):3053-3061. doi: 10.1007/s11136-023-03451-9. Epub 2023 Jul 13.

  PMID: 37439961 DERIVED

• Turkoz I, Lopena O, Salvadore G, Sanacora G, Shelton R, Fu DJ. Treatment response to esketamine nasal spray in patients with major depressive disorder and acute suicidal ideation or behavior without evidence of early response: a pooled post hoc analysis of ASPIRE. CNS Spectr. 2023 Aug;28(4):482-488. doi: 10.1017/S1092852922000931. Epub 2022 Jul 29.

  PMID: 35904046 DERIVED

• 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.

  PMID: 35816217 DERIVED

• 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.

  PMID: 34510411 DERIVED

• 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.

  PMID: 32861217 DERIVED

Related Links

• 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 (Aspire II)

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Esketamine; Standard of Care

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Limitations and Caveats

Esketamine's known characteristic effects such as dissociative symptoms, sedation, and elevation of blood pressure may have impact on blinding, to minimize this bias, protocol specified that different raters perform efficacy and safety assessments.

Results Point of Contact

• Title: Senior Director
• Organization: Janssen Research & Development, LLC

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: March 27, 2017
• First Posted: March 31, 2017
• Study Start: June 15, 2017
• Primary Completion: April 11, 2019
• Study Completion: April 11, 2019
• Last Updated: April 29, 2025
• Results First Posted: September 25, 2020

Record last verified: 2025-04

Locations

ES (4); PL (4); TU (4); LI (3); AR (4); CA (2); US (18); AU (2); BE (3); BR (6); CZ (5); FR (6)