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

NCT03039192 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: CR1082842016-003990-1754135419SUI3001
• Study Type: interventional
• Target: 226
• Locations: 10 countries
• Sites: 54

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.

Conditions

Depressive Disorder, Major

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score at 24 Hours After the First Dose (Day 2) (Last Observation Carried Forward [LOCF] Data) During Double-blind 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)

Secondary Outcomes (22)

• Change From Baseline in Clinical Global Impression of Severity of Suicidality- Revised (CGI-SS-R) Score at 24 Hours After the First Dose (Day 2) (LOCF Data) During Double-blind Phase

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

• Number of Participants Who Achieved Remission (MADRS Total Score Less Than or Equal to [<=] 12) Through the Double-blind Phase

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

• Change From Baseline in Montgomery Asberg Depression Rating Scale Total Score at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25 During Double-blind Phase

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

• Change From Baseline in Clinical Global Impression- Severity of Suicidality-Revised (CGI-SS-R) at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25 During Double-blind Phase

  Baseline and Days 1, 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) Through Double-blind Phase

  Days 1, 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) 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.

Drug: Esketamine; Other: Standard of Care

Placebo + Standard of care

PLACEBO COMPARATOR

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.

Other: Placebo; Other: Standard of Care

Interventions

Esketamine DRUG

Intranasal esketamine solution 84 milligram (mg)

Esketamine + Standard of care

Placebo OTHER

Intranasal Placebo solution

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)
• 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

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. 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (56)

UAB Department of Psychiatry and Behavioral Neurobiology

Birmingham, Alabama, 35294, United States

Location

Metropolitan Neuro Behavioral Institute

Chandler, Arizona, 85226, United States

Location

Collaborative NeuroScience Network

Garden Grove, California, 92845, United States

Location

Yale University

New Haven, Connecticut, 06511, United States

Location

Rush University

Chicago, Illinois, 60612, United States

Location

Alexian Behavioral Health Hospital

Hoffman Estates, Illinois, 60169, United States

Location

University of Louisville Department of Psychiatry

Louisville, Kentucky, 40202, United States

Location

LSU Health Sciences Center New Orleans

New Orleans, Louisiana, 70115, United States

Location

Louisiana Clinical Research

Shreveport, Louisiana, 71101, United States

Location

Sheppard Pratt Health System

Baltimore, Maryland, 21204, United States

Location

CBH Health

Gaithersburg, Maryland, 20877, United States

Location

State University of New York

Buffalo, New York, 14215, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Clinical Trials of America

Hickory, North Carolina, 28601, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75235, United States

Location

Regional Psychiatric Dispansery

Bulgaria, 7003, Bulgaria

Location

Mental Health Center Prof. Dr. Ivan Temkov

Burgas, 8001, Bulgaria

Location

State Psychiatric Hospital - Lovech

Lovech, 5500, Bulgaria

Location

UMHAT 'Sveti Georgi'-Plovdiv

Plovdiv, 4002, Bulgaria

Location

Military Medical Academy Multiprofile Hospital for Active Treatment Sofia

Sofia, 1606, Bulgaria

Location

North Estonian Medical Centre Foundation

Tallinn, 10614, Estonia

Location

Tartu University Hospital

Tartu, 50417, Estonia

Location

Vivantes Humboldt Klinikum

Berlin, 13509, Germany

Location

Universitatsklinikum Frankfurt

Frankfurt am Main, 60528, Germany

Location

Klinik für Psychiatrie und Psychotherapie

Freiburg im Breisgau, 79104, Germany

Location

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

Budapest, 1125, Hungary

Location

Semmelweis Egyetem Kútvölgyi Klinikai Tömb

Budapest, 1125, Hungary

Location

Nyiro Gyula Korhaz

Budapest, 1135, Hungary

Location

Petz Aladar Megyei Oktato Korhaz

Győr, H-9024, Hungary

Location

Pecsi Tudomanyegyetem Klinikai Kozpont

Pécs, 7623, Hungary

Location

University Kebangsaan Malaysia Medical Centre

Cheras, 56000, Malaysia

Location

Hospital Kuala Lumpur

Kuala Lumpur, 50586, Malaysia

Location

University Malaya Medical Centre

Kuala Lumpur, 59100, Malaysia

Location

Hospital Tuanku Jaafar

Seremban, 70300, Malaysia

Location

Fakultna nemocnica s poliklinikou v Ziline

Žilina, 012 07, Slovakia

Location

Flexivest 14 Research

Cape Town, 7550, South Africa

Location

Juan Schrönen - Western Cape South Africa

Welgemoed, 7530, South Africa

Location

Chonnam National University Hospital

Gwangju, 61469, South Korea

Location

Korea University Ansan Hospital

Gyeonggi-do, 15355, South Korea

Location

Kyung Hee University Medical Center

Seoul, 02447, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Seoul National University Hospital

Seoul, 3080, South Korea

Location

Hosp. Univ. Fundacion Alcorcon

Alcorcón, 28922, Spain

Location

Hosp Univ Vall D Hebron

Barcelona, 08035, Spain

Location

Hosp Clinic de Barcelona

Barcelona, 08036, Spain

Location

Inst. Internac. Neurociencias Aplicadas

Barcelona, 8006, Spain

Location

Hosp. Univ. de Basurto

Bilbao, 48013, Spain

Location

Hosp. Univ. Ramon Y Cajal

Madrid, 28034, Spain

Location

Clinica Univ. de Navarra

Pamplona, 31008, Spain

Location

Benito Menni Comp. Asist. Salut Mental

Sant Boi de Llobregat, 08830, Spain

Location

Tri-Service Genaral Hospital

Neihu District, 114, Taiwan

Location

Taipei Medical University Shuang Ho Hospital

New Taipei City, 23561, Taiwan

Location

Chung Shan Medical University Hospital

Taichung, 40201, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Related Publications (7)

• 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

• 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.

  PMID: 34412104 DERIVED

• 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.

  PMID: 32412700 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 I)

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

Study Record Dates

• First Submitted: January 31, 2017
• First Posted: February 1, 2017
• Study Start: June 9, 2017
• Primary Completion: December 18, 2018
• Study Completion: December 18, 2018
• Last Updated: April 29, 2025
• Results First Posted: October 29, 2020

Record last verified: 2025-04

Locations

ZA (2); DE (3); KR (5); ES (8); US (17); HU (5); MY (4); TW (4); BU (5); SL (1)