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

NCT ID: NCT03097133

Last Updated: 2025-04-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 230 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-15
• Study Completion Date: 2019-04-11

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.

Conditions

Depressive Disorder, Major

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Esketamine + Standard of care

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.

Group Type: EXPERIMENTAL

Esketamine

Intervention Type: 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).

Standard of Care

Intervention Type: 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.

Placebo + Standard of care

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Standard of Care

Intervention Type: 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.

Interventions

Esketamine

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).

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Standard of Care

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.

Intervention Type: OTHER

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

University of California San Diego/Psychiatry

San Diego, California, United States

Sharp Mesa Vista Hospital

San Diego, California, United States

University of Conneticut School of Medicine

Farmington, Connecticut, United States

University of Miami Health System

Miami, Florida, United States

Innovative Clinical Research Inc

North Miami, Florida, United States

University of South Florida

Tampa, Florida, United States

Atlanta Behavioral Research, LLC

Atlanta, Georgia, United States

Memorial Medical Center

Springfield, Illinois, United States

Neuroscience Research Institute

Winfield, Illinois, United States

Lake Charles Clinical Trials

Lake Charles, Louisiana, United States

John Hopkins Hospital

Baltimore, Maryland, United States

Altea Research Institute

Las Vegas, Nevada, United States

The Zucker Hillside Hospital

Glen Oaks, New York, United States

Stony Brook University Medical Center

Stony Brook, New York, United States

University of North Carolina

Chapel Hill, North Carolina, United States

University of Cincinnati, Dept of Psychiatry & Behavioral Neuroscience

Cincinnati, Ohio, United States

East Tennessee State University

Johnson City, Tennessee, United States

University of Wisconsin Medical Center

Madison, Wisconsin, United States

Clínica Privada Banfield S.A

Banfield, , Argentina

Hospital Fleni

Ciudad de Buenos Aires, , Argentina

Sanatorio Prof. Leon S. Morra

Córdoba, , Argentina

Clinica Privada de Salud Mental Santa Teresa de Ávila

La Plata, , Argentina

Medical University Vienna MUV

Vienna, , Austria

Klinikum Wels Grieskirchen

Wels, , Austria

AZ Sint Jan Brugge Oostende AV

Bruges, , Belgium

UZ Gent

Ghent, , Belgium

ARIADNE

Lede, , Belgium

Universidade Federal De Minas Gerais - Hospital das Clínicas

Belo Horizonte, , Brazil

Universidade Federal Do Ceara

Fortaleza, , Brazil

Instituto Bairral de Psiquiatria

Itapira, , Brazil

Hospital Universitario Professor Edgar Santos

Salvador, , Brazil

CEMEC - Centro Multidisciplinar de Estudos Clínicos

Santo André, , Brazil

Hospital Das Clinicas Da Faculdade De Medicina Da USP

São Paulo, , Brazil

St. Michael's Hospital

Toronto, Ontario, Canada

Institut universitaire en sante mentale de Montreal

Montreal, Quebec, Canada

Fakultni nemocnice Brno

Brno, , Czechia

Nemocnice s pol. Havirov, p.o.

Havířov, , Czechia

Narodni ustav dusevniho zdravi

Klecany, , Czechia

Vseobecna Fakultní Nemocnice

Prague, , Czechia

Ústrední vojenské nemocnice Praha

Prague, , Czechia

Hôpital de Bohars

Bohars, , France

CHRU Montpellier Hopital Lapeyronie

Montpellier, , France

CHU Caremeau

Nîmes, , France

Hopital Sainte Anne

Paris, , France

CHU Saint Etienne Hopital Nord

Saint-Priest-en-Jarez, , France

CHU Toulouse

Toulouse, , France

Hospital of Lithuanian University of Health Sciences Kaunas Clinics

Kaunas, , Lithuania

Republic Kaunas Hospital

Kaunas County, , Lithuania

Vilnius Mental Health Center

Vilnius, , Lithuania

Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

Szpital Specjalistyczny im H Klimontowicza Oddzial Psychiatryczny

Gorlice, , Poland

SPZOZ CSK UM w Lodzi Klinika Zaburzen Afektywnych i Psychotycznych

Lodz, , Poland

Klinika Psychiatryczna WUM Mazowieckie Specjalistyczne Centrum Zdrowia im prof Jana Mazurkiewicza

Pruszków, , Poland

Hosp Univ Vall D Hebron

Barcelona, , Spain

Inst. Internac. Neurociencias Aplicadas

Barcelona, , Spain

Hosp. Univ. de Basurto

Bilbao, , Spain

Clinica Univ. de Navarra

Pamplona, , Spain

Bursa Sevket Yilmaz Research and Training Hospital

Bursa, , Turkey (Türkiye)

Uludag University Medical Faculty

Bursa, , Turkey (Türkiye)

Sisli Etfal Research Training Hospital

Istanbul, , Turkey (Türkiye)

Samsun Psychiatric Hospital

Samsun, , Turkey (Türkiye)

Countries

United States; Argentina; Austria; Belgium; Brazil; Canada; Czechia; France; Lithuania; Poland; Spain; Turkey (Türkiye)

References

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.

Reference Type: DERIVED

PMID: 37568081 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37439961 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35904046 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35816217 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34510411 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32861217 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217051&parentIdentifier=CR108285&attachmentIdentifier=6345e95c-007a-4ab5-b5f6-736c8099e66f&fileName=54135419SUI3002_(CR108285)_Additional_Results_Data_CH.pdf&versionIdentifier=

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)

Other Identifiers

2016-003992-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

54135419SUI3002

Identifier Type: OTHER

Identifier Source: secondary_id

CR108285

Identifier Type: -

Identifier Source: org_study_id