54135419SUI3001: 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: NCT03039192

Last Updated: 2025-04-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 226 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-09
• Study Completion Date: 2018-12-18

Brief Summary

The purpose of the 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

This is a randomized (study medication assigned to participants by chance), double-blind (neither the researchers nor the participants know what treatment the participant is receiving), placebo-controlled (an inactive substance which contains no drug) that is compared in a clinical trial with a drug to test if the drug has a real effect), multicenter (when more than one hospital or study team work on a medical research study) study. Study will enroll participants with suicidal ideation who are assessed to be at imminent risk for suicide. The study will consist of a screening evaluation performed within 48 hours prior to the Day 1 intranasal dose immediately followed by a 25-day double-blind treatment phase (Day 1 to 25), and a 65 day follow-up phase (Day 26 to Day 90). The total study duration for each subject will be approximately 13 weeks. Participants' safety will be evaluated throughout the study. 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) two times per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) along with standard of care (SOC) antidepressant treatment.

Group Type: EXPERIMENTAL

Esketamine

Intervention Type: DRUG

Intranasal esketamine solution 84 milligram (mg)

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 two times per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) along with standard of care antidepressant treatment.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Intranasal Placebo solution

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

Intranasal esketamine solution 84 milligram (mg)

Intervention Type: DRUG

Placebo

Intranasal Placebo solution

Intervention Type: OTHER

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)
• In the physician's opinion, acute psychiatric hospitalization is clinically warranted due to participant's imminent risk of suicide
• 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. Note: the response to B3 must refer to the present, whereas the response to B10 may reflect the past 24 hours. If the screening period is longer than 24 hours, assessment of B3 and B10 of MINI must be repeated prior to randomization to confirm eligibility
• 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 5 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)
• Participant is comfortable with self-administration of intranasal medication and able to follow instructions provided

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. 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 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

• 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

UAB Department of Psychiatry and Behavioral Neurobiology

Birmingham, Alabama, United States

Metropolitan Neuro Behavioral Institute

Chandler, Arizona, United States

Collaborative NeuroScience Network

Garden Grove, California, United States

Yale University

New Haven, Connecticut, United States

Rush University

Chicago, Illinois, United States

Alexian Behavioral Health Hospital

Hoffman Estates, Illinois, United States

University of Louisville Department of Psychiatry

Louisville, Kentucky, United States

LSU Health Sciences Center New Orleans

New Orleans, Louisiana, United States

Louisiana Clinical Research

Shreveport, Louisiana, United States

Sheppard Pratt Health System

Baltimore, Maryland, United States

CBH Health

Gaithersburg, Maryland, United States

State University of New York

Buffalo, New York, United States

Columbia University Medical Center

New York, New York, United States

Clinical Trials of America

Hickory, North Carolina, United States

The Ohio State University

Columbus, Ohio, United States

Medical University of South Carolina

Charleston, South Carolina, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Regional Psychiatric Dispansery

Bulgaria, , Bulgaria

Mental Health Center Prof. Dr. Ivan Temkov

Burgas, , Bulgaria

State Psychiatric Hospital - Lovech

Lovech, , Bulgaria

UMHAT 'Sveti Georgi'-Plovdiv

Plovdiv, , Bulgaria

Military Medical Academy Multiprofile Hospital for Active Treatment Sofia

Sofia, , Bulgaria

North Estonian Medical Centre Foundation

Tallinn, , Estonia

Tartu University Hospital

Tartu, , Estonia

Vivantes Humboldt Klinikum

Berlin, , Germany

Universitatsklinikum Frankfurt

Frankfurt am Main, , Germany

Klinik für Psychiatrie und Psychotherapie

Freiburg im Breisgau, , Germany

Eszak Kozep budai Centrum Uj Szent Janos Korhaz es Szakrendelo Budai Csaladkozpontu

Budapest, , Hungary

Semmelweis Egyetem Kútvölgyi Klinikai Tömb

Budapest, , Hungary

Nyiro Gyula Korhaz

Budapest, , Hungary

Petz Aladar Megyei Oktato Korhaz

Győr, , Hungary

Pecsi Tudomanyegyetem Klinikai Kozpont

Pécs, , Hungary

University Kebangsaan Malaysia Medical Centre

Cheras, , Malaysia

Hospital Kuala Lumpur

Kuala Lumpur, , Malaysia

University Malaya Medical Centre

Kuala Lumpur, , Malaysia

Hospital Tuanku Jaafar

Seremban, , Malaysia

Fakultna nemocnica s poliklinikou v Ziline

Žilina, , Slovakia

Flexivest 14 Research

Cape Town, , South Africa

Juan Schrönen - Western Cape South Africa

Welgemoed, , South Africa

Chonnam National University Hospital

Gwangju, , South Korea

Korea University Ansan Hospital

Gyeonggi-do, , South Korea

Kyung Hee University Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Hosp. Univ. Fundacion Alcorcon

Alcorcón, , Spain

Hosp Univ Vall D Hebron

Barcelona, , Spain

Hosp Clinic de Barcelona

Barcelona, , Spain

Inst. Internac. Neurociencias Aplicadas

Barcelona, , Spain

Hosp. Univ. de Basurto

Bilbao, , Spain

Hosp. Univ. Ramon Y Cajal

Madrid, , Spain

Clinica Univ. de Navarra

Pamplona, , Spain

Benito Menni Comp. Asist. Salut Mental

Sant Boi de Llobregat, , Spain

Tri-Service Genaral Hospital

Neihu District, , Taiwan

Taipei Medical University Shuang Ho Hospital

New Taipei City, , Taiwan

Chung Shan Medical University Hospital

Taichung, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

Countries

United States; Bulgaria; Estonia; Germany; Hungary; Malaysia; Slovakia; South Africa; South Korea; Spain; Taiwan

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)

Canuso CM, Ionescu DF, Li X, Qiu X, Lane R, Turkoz I, Nash AI, Lopena TJ, Fu DJ. Esketamine Nasal Spray for the Rapid Reduction of Depressive Symptoms in Major Depressive Disorder With Acute Suicidal Ideation or Behavior. J Clin Psychopharmacol. 2021 Sep-Oct 01;41(5):516-524. doi: 10.1097/JCP.0000000000001465.

Reference Type: DERIVED

PMID: 34412104 (View on PubMed)

Fu DJ, Ionescu DF, Li X, Lane R, Lim P, Sanacora G, Hough D, Manji H, Drevets WC, Canuso CM. Esketamine Nasal Spray for Rapid Reduction of Major Depressive Disorder Symptoms in Patients Who Have Active Suicidal Ideation With Intent: Double-Blind, Randomized Study (ASPIRE I). J Clin Psychiatry. 2020 May 12;81(3):19m13191. doi: 10.4088/JCP.19m13191.

Reference Type: DERIVED

PMID: 32412700 (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=CR108284&attachmentIdentifier=0b008702-9e7b-4d11-b853-d3aba96bb3a1&fileName=54135419SUI3001_(CR108284)_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 I)

Other Identifiers

2016-003990-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

54135419SUI3001

Identifier Type: OTHER

Identifier Source: secondary_id

CR108284

Identifier Type: -

Identifier Source: org_study_id