Clinical trial NCT03039192: 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
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: 2017-02-01
Enrollment: 226
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 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.

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

Primary outcomes:
measure: 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
timeFrame: Baseline (Day 1, predose) and 24 hours first post dose (Day 2)
Secondary outcomes:
measure: 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
timeFrame: Baseline (Day 1, predose) and 24 hours first post dose (Day 2)
measure: Number of Participants Who Achieved Remission (MADRS Total Score Less Than or Equal to [<=] 12) Through the Double-blind Phase
timeFrame: Days 1 (4 hours postdose), 2, 4, 8, 11, 15, 18, 22 and Day 25 (predose and 4 hours postdose)
measure: 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
timeFrame: Baseline and Days 1, 2, 4, 8, 11, 15, 18, 22 and 25 (predose and 4 hours postdose)
measure: 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
timeFrame: Baseline and Days 1, 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) Through Double-blind Phase
timeFrame: Days 1, 2, 4, 8, 11, 15, 18, 22 and 25
measure: Change From Baseline in Clinical Global Impression of Imminent Suicide Risk (CGI-SR-I) Scale Total Score at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25 During Double-blind Phase
timeFrame: Baseline and Days 1, 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 During Double-blind Phase
timeFrame: Baseline, Days 8 and 25
measure: Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) at Days 2, 11 and 25 During Double-blind Phase: Health Status Index
timeFrame: Baseline and Days 2, 11 and 25
measure: Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) at Days 2, 11 and 25 During Double-blind Phase: EQ-Visual Analogue Scale (EQ-VAS)
timeFrame: Baseline, Days 2, 11 and 25
measure: Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) at Days 2, 11 and 25 During Double-blind Phase: Sum Score
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 During Double-blind Phase
timeFrame: Baseline and Days 2, 11 and 25
measure: Treatment Satisfaction Questionnaire for Medication (TSQM-9) Total Score at Days 15 and 25 During Double-blind Phase
timeFrame: Days 15 and 25
measure: Change From Baseline in Suicide Ideation and Behavior Assessment Tool (SIBAT) Module 5 (My Risk) Question 3 (Patient-reported FoST) Total Score at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25 During Double-blind Phase
timeFrame: Baseline, Days 1, 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 FoST Total Score at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25 During Double-blind Phase
timeFrame: Baseline and Days 1, 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: Birmingham
country: United States
facility: UAB Department of Psychiatry and Behavioral Neurobiology
state: Alabama
city: Chandler
country: United States
facility: Metropolitan Neuro Behavioral Institute
state: Arizona
city: Garden Grove
country: United States
facility: Collaborative NeuroScience Network
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Chicago
country: United States
facility: Rush University
state: Illinois
city: Hoffman Estates
country: United States
facility: Alexian Behavioral Health Hospital
state: Illinois
city: Louisville
country: United States
facility: University of Louisville Department of Psychiatry
state: Kentucky
city: New Orleans
country: United States
facility: LSU Health Sciences Center New Orleans
state: Louisiana
city: Shreveport
country: United States
facility: Louisiana Clinical Research
state: Louisiana
city: Baltimore
country: United States
facility: Sheppard Pratt Health System
state: Maryland
city: Gaithersburg
country: United States
facility: CBH Health
state: Maryland
city: Buffalo
country: United States
facility: State University of New York
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Hickory
country: United States
facility: Clinical Trials of America
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Bourgas
country: Bulgaria
facility: Mental Health Center Prof. Dr. Ivan Temkov
city: Bulgaria
country: Bulgaria
facility: Regional Psychiatric Dispansery
city: Lovech
country: Bulgaria
facility: State Psychiatric Hospital - Lovech
city: Plovdiv
country: Bulgaria
facility: UMHAT 'Sveti Georgi'-Plovdiv
city: Sofia
country: Bulgaria
facility: Military Medical Academy Multiprofile Hospital for Active Treatment Sofia
city: Tallinn
country: Estonia
facility: North Estonian Medical Centre Foundation
city: Tartu
country: Estonia
facility: Tartu University Hospital
city: Berlin
country: Germany
facility: Vivantes Humboldt Klinikum
city: Frankfurt Am Main
country: Germany
facility: Universitatsklinikum Frankfurt
city: Freiburg
country: Germany
facility: Klinik für Psychiatrie und Psychotherapie
city: Budapest
country: Hungary
facility: Eszak Kozep budai Centrum Uj Szent Janos Korhaz es Szakrendelo Budai Csaladkozpontu
city: Budapest
country: Hungary
facility: Semmelweis Egyetem Kútvölgyi Klinikai Tömb
city: Budapest
country: Hungary
facility: Nyiro Gyula Korhaz
city: Gyor
country: Hungary
facility: Petz Aladar Megyei Oktato Korhaz
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem Klinikai Kozpont
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: Korea University Ansan Hospital
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Cheras
country: Malaysia
facility: University Kebangsaan Malaysia Medical Centre
city: Kuala Lumpur
country: Malaysia
facility: Hospital Kuala Lumpur
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
city: Seremban
country: Malaysia
facility: Hospital Tuanku Jaafar
city: Zilina
country: Slovakia
facility: Fakultna nemocnica s poliklinikou v Ziline
city: Cape Town
country: South Africa
facility: Flexivest 14 Research
city: Welgemoed
country: South Africa
facility: Juan Schrönen - Western Cape South Africa
city: Alcorcón
country: Spain
facility: Hosp. Univ. Fundacion Alcorcon
city: Barcelona
country: Spain
facility: Hosp Univ Vall D Hebron
city: Barcelona
country: Spain
facility: Hosp Clinic de Barcelona
city: Barcelona
country: Spain
facility: Inst. Internac. Neurociencias Aplicadas
city: Bilbao
country: Spain
facility: Hosp. Univ. de Basurto
city: Madrid
country: Spain
facility: Hosp. Univ. Ramon Y Cajal
city: Pamplona
country: Spain
facility: Clinica Univ. de Navarra
city: Sant Boi de Llobregat
country: Spain
facility: Benito Menni Comp. Asist. Salut Mental
city: Neihu District
country: Taiwan
facility: Tri-Service Genaral Hospital
city: New Taipei City
country: Taiwan
facility: Taipei Medical University Shuang Ho Hospital
city: Taichung
country: Taiwan
facility: Chung Shan Medical University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General 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: 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.
citation: 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.