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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 (Aspire I)

Primary Purpose

Depressive Disorder, Major

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Esketamine

Placebo

Standard of Care

About this trial

This is an interventional treatment trial for Depressive Disorder, Major

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

UAB Department of Psychiatry and Behavioral Neurobiology
Metropolitan Neuro Behavioral Institute
Collaborative NeuroScience Network
Yale University
Rush University
Alexian Behavioral Health Hospital
University of Louisville, Department of Psychiatry
LSU Health Sciences Center New Orleans
Louisiana Clinical Research
Sheppard Pratt Health System
CBH Health
State University of New York
Columbia University Medical Center
Clinical Trials of America
The Ohio State University
Medical University of South Carolina
University of Texas Southwestern Medical Center
Mental Health Center Prof. Dr. Ivan Temkov
Regional Psychiatric Dispansery
State Psychiatric Hospital - Lovech
UMHAT 'Sveti Georgi'-Plovdiv
Military Medical Academy, Multiprofile Hospital for Active Treatment -Sofia
North Estonian Medical Centre Foundation
Tartu University Hospital
Vivantes Humboldt Klinikum
Universitatsklinikum Frankfurt
Klinik für Psychiatrie und Psychotherapie
Semmelweis Egyetem Kútvölgyi Klinikai Tömb
Szent János Kórház és Észak-budai Egyesített Kórházak
Nyírő Gyula Kórház
Petz Aladar Megyei Oktato Korhaz
Pecsi Tudomanyegyetem Klinikai Kozpont
Korea University Ansan Hospital
Chonnam National University Hospital
Kyung Hee University Medical Center
Samsung Medical Center
Seoul National University Hospital
University Kebangsaan Malaysia Medical Centre
Hospital Kuala Lumpur
University Malaya Medical Centre
Hospital Tuanku Jaafar
Fakultna nemocnica s poliklinikou v Ziline
Flexivest 14 Research
Juan Schrönen - Western Cape South Africa
Hosp. Univ. Fundacion Alcorcon
Hosp. Univ. Vall D'Hebron
Hosp. Clinic I Provincial de Barcelona
Inst. Internac. Neurociencias Aplicadas
Hosp. Univ. de Basurto
Hosp. Univ. Ramon Y Cajal
Clinica Univ. de Navarra
Benito Menni Comp. Asist. Salut Mental
Tri-Service Genaral Hospital
Taipei Medical University Shuang Ho Hospital
Chung Shan Medical University Hospital
Taipei Veterans General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Esketamine + Standard of care

Placebo + Standard of care

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

CGI-SS-R was derived from 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 rating is scored on a 7-point scale from 0 (normal, not at all suicidal) to 6 (among the most extremely suicidal participants). A higher score indicates a more severe condition and a reduction in score indicates improvement (that is, lower severity of suicidality).

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

Participants who had a MADRS total score of <=12 were considered remitters. MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition and a negative change in score indicates improvement.

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

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

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

Number of Participants Who Achieved Resolution of Suicidality (CGI-SS-R Score of 0 or 1) Through Double-blind Phase

CGI-SS-R was derived from 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 rating is scored on a 7-point scale from 0 (normal, not at all suicidal) to 6 (among the most extremely suicidal participants). A higher score indicates a more severe condition. Negative change in score indicates improvement. A participant was considered to achieve resolution of suicidality at a given time point if the CGI-SS-R score was 0 (normal, not at all suicidal) or 1 (questionably suicidal).

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

The CGI-SR-I is a scale summarizing the clinician's best assessment of the likelihood that the participant will attempt suicide in the next 7 days. The CGI-SR-I rating is scored on a 7-point scale: where' 0 (no imminent suicide risk); 1 (minimal imminent suicide risk), 2 (mild imminent suicide risk), 3 (moderate imminent suicide risk), 4 (marked imminent suicide risk), 5 (severely imminent suicide risk), 6 (extreme imminent suicide risk). Higher score indicates a more severe condition. Negative change in score indicates improvement.

Change From Baseline in Beck Hopelessness Scale (BHS) Total Score at Days 8 and 25 During Double-blind Phase

BHS is a self-reported measure to assess one's level of negative expectations or pessimism regarding future. It consists of 20 true-false items that examine respondent's attitude over past week by either endorsing a pessimistic statement or denying an optimistic statement; 9 are keyed false and 11 are keyed true. For every statement, each response was assigned score of 0 or 1. Total BHS score is sum of item responses, ranged from 0-20, where higher score represented higher level of hopelessness.

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

EQ-5D-5L measures health outcome. It consists of EQ-5D-5L descriptive system and EQ visual analogue scale (EQ-VAS). EQ-5D-5L system comprises following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each of 5 dimensions is divided into 5 levels of perceived problems (Level 1-no problem, Level 2-slight problems, Level 3-moderate problems, Level 4-severe problems, Level 5-extreme problems). Participant selects answer for each of 5 dimensions considering response that best matches his/her health "today". Responses were used to generate a health status index (HSI). Health Status Index ranges from 0.148 - 0.949, anchored at 0 (dead) and 1 (full health). Positive change in score indicates improvement.

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)

EQ-5D-5L measures health outcome. It consists of EQ-5D-5L descriptive system and the EQ visual analogue scale (EQ-VAS). EQ-VAS score from 0 (worst health) to 100 (best health), positive change in score indicates improvement.

Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) at Days 2, 11 and 25 During Double-blind Phase: Sum Score

EQ-5D-5L measures health outcome. It consists of EQ-5D-5L system and EQ-VAS. EQ-5D-5L system comprises following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each of 5 dimensions is divided into 5 levels of perceived problems (Level 1-no problem, Level 2-slight problems, Level 3-moderate problems, Level 4-severe problems, and Level 5-extreme problems). Participant selects answer for each of 5 dimensions considering response that best matches his/her health "today". Responses were used to generate a health status index (HSI). Health Status Index ranges from 0.148 - 0.949, anchored at 0 (dead) and 1 (full health), a lower score indicates worse health. Sum score=(sum of the scores from the 5 dimensions minus 5)*5. Sum score ranges from 0-100. Higher score indicates a more severe problem. Negative change in score indicates improvement.

Change From Baseline in Quality of Life in Depression Scale (QLDS) Total Score at Days 2, 11 and 25 During Double-blind Phase

The QLDS is a disease specific patient-reported outcome designed to assess health related quality of life in participants with major depressive disorder (MDD). The instrument has a recall period of "at the moment", contains 34-items with "true"/"not true" response options and takes approximately 5-10 minutes to complete. The total score range is from 0 (good quality of life) to 34 (very poor quality of life). A higher score indicates a more severe condition. Negative change indicates improvement.

Treatment Satisfaction Questionnaire for Medication (TSQM-9) Total Score at Days 15 and 25 During Double-blind Phase

The TSQM-9 is a 9-item generic patient-reported outcome instrument to assess participants' satisfaction with medication. It covers domains of effectiveness, convenience, and global satisfaction. The TSQM-9 domain scores were calculated as recommended by the instrument authors. (i) Effectiveness = [(item 1 + item 2 + item 3) - 3]/18*100, (ii) Convenience = [(item 4 + item 5 + item 6) - 3]/18*100 and (iii) Global satisfaction = [(item 7 + item 8 + item 9) - 3]/14*100. Each domain score can be calculated only if all the three items considered in the calculation of that score are not missing. The TSQM-9 domain score ranges from 0 to 100, with higher scores representing higher satisfaction.

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

SIBAT is an assessment tool that captures suicidal ideation, behavior, and risk. It permits assessment of change in suicidal ideation and behavior and documents clinician assessment of severity of suicidality and suicide risk. SIBAT is organized into 8 modules divided into 2 major divisions: patient-reported section (Modules 1-5) and clinician-rated section (Modules 6-8). Patient-reported section has modules of demographics and suicide history, risk/protective factors, suicidal thinking, suicide behavior, and suicide risk. Question 3 from Module 5 asks participants to describe their thinking about suicide right now from 5 response options ranging from 0 (I have no suicidal thoughts) to 4 (I have suicidal thoughts all of time). SIBAT Module 5 (My Risk) Question 3 (Patient-reported FoST) total score ranges from 0 to 4; a higher score indicates a more severe condition. Negative change in score indicates improvement.

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

SIBAT is assessment tool that captures suicidal ideation, behavior, and risk. It permits assessment of change in suicidal ideation and behavior and documents clinician assessment of severity of suicidality and suicide risk. SIBAT has 8 modules divided into 2 major divisions: patient-reported section (Modules 1-5) and clinician-rated section (Modules 6-8). Clinician-rated section has modules for semi-structured interview, clinical global impressions of current severity of suicidality and imminent suicide risk, clinical global impression of long-term suicide risk, and clinical judgment of optimal suicide management. The score anchor point as in participant report frequency of suicidal thinking (FoST) that is, response options from never to all the time. Module 7-FoST score ranges from 0-5; higher score indicates more severe condition. Negative change in score indicates improvement.

Number of Participants With Treatment Emergent Adverse Events (TEAEs): DB Treatment Phase

An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non investigational) product, whether or not related to that medicinal (investigational or non-investigational) product. A TEAE is categorized as related if assessed by the investigator as possibly, probably, or very likely related to study agent.

Number of Participants With Treatment Emergent Abnormal Laboratory Values: DB Treatment Phase

Low/high abnormal values are: Alanine aminotransferase (ALT)-high=200 Units per liter(U/L); ALP-high=250U/L; aspartate aminotransferase(AST)-high=250U/L; gamma glutamyl transferase(GGT)=300U/L; Albumin(low=24g/L,high=60 g/L); Bicarbonate(low=15.1, high=34.9mmol/L); Bilirubin(high=51.3micromol/L); calcium(low=1.5,high=3mmol/L);Chloride(low=94,high=112mmol/L); CK(High=990U/L); Creatinine(High=265.2micromol/L); Eosinophils(High=10%); Erythrocytes(low=3.0*1012/L,high=6.4*1012/L); Glucose(low=2.2,high=16.7mmol/L); Hemoglobin(low=80g/L,high=190g/L);Hematocrit(low=0.28, high=0.55 fraction); LD(high=500U/L); Leukocytes(low=2.5*109/L,high=15.5*109/L); Lymphocytes(low=10%,high=60%); Monocytes(high=20%); Neutrophils(low=30%,high=90%); Phosphate(low=0.7 mmol/L,high=2.6mmol/L); Platelet count(low=100*109/L,high=600*109/L]; Potassium(low=3.0mmol/L,high=5.8 mmol/L]; Protein(low=50 g/L); Sodium(low=125 mmol/L,high=155 mmol/L); Urate(low=89.2 micromol/L,high=594.8micromol/L); Urine(high=8.0 pH).

Number of Participants With Abnormal Nasal Examinations at Day 25: DB Treatment Phase

Number of participants with abnormal nasal examination were reported. Nasal examination of visual inspection of the epistaxis, nasal crusts, nasal discharge, and nasal erythema was performed.

Number of Participants With Treatment Emergent Abnormal Electrocardiogram (ECG) Values at Any Time: DB Treatment Phase

Number of participants with treatment emergent abnormal ECG values for variables including heart rate (abnormally low refers to less than or equal to [<=] 50 beats per minute [bpm] , abnormally high refers greater than or equal to [>=] 100 bpm), pulse rate (PR) interval (abnormally high refers to >= 210 milliseconds [msec]), QRS interval (abnormally Low refers to <= 50, abnormally high refers to >= 120 msec) and QT interval (abnormally low refers to <= 200, abnormally high >= 500 msec) were reported.

Number of Participants With Abnormal Arterial Oxygen Saturation (SpO2) Levels (Less Than [<] 93%) as Assessed by Pulse Oximetry at Any Time: DB Treatment Phase

Pulse oximetry was used to measure arterial SpO2 levels. On each dosing day, the device was attached to the finger, toe, or ear, and SpO2 was monitored and documented. If oxygen saturation levels were less than (<) 93% at any time during the 1.5 hours postdose interval, pulse oximetry was recorded every 5 minutes until levels return to >= 93% or until the participant is referred for appropriate medical care, if clinically indicated. Participants with at least 2 consecutive postdose oxygen saturation below 93% during the DB treatment phase were reported.

Number of Participants With Treatment Emergent Vital Signs Abnormalities: DB Treatment Phase

Number of participants with treatment emergent vital signs abnormalities (pulse rate in bpm [abnormally low = a decrease from baseline of >= 15 to a value <= 50; abnormally high = an increase from baseline of >=15 to a value >=100] , systolic blood pressure [SBP] in mmHg [abnormally low = a decrease from baseline of >= 20 to a value <= 90; abnormally high = an increase from baseline of >= 20 to a value >= 180], and diastolic blood pressure [DBP] in mmHg [abnormally low= a decrease from baseline of >=15 to a value <= 50; abnormally high = an increase from baseline of >= 15 to a value >= 105) were reported.

Number of Sedated Participants as Assessed by Modified Observer's Assessment of Alertness/Sedation (MOAA/S) Score at Any Time: DB Treatment Phase

MOAA/S was used to measure treatment-emergent sedation with correlation to levels of sedation defined by the American society of anesthesiologists (ASA) continuum. The MOAA/S scores range from 0 to 5 where,0 = no response to painful stimulus; ASA continuum = general anesthesia, 1 = responds to trapezius squeeze; ASA continuum = deep sedation, 2 = purposeful response to mild prodding or mild shaking; ASA continuum = moderate sedation, 3 = responds after name called loudly or repeatedly; ASA continuum = moderate sedation, 4 = lethargic response to name spoken in normal tone; ASA continuum = moderate sedation and 5 = readily responds to name spoken in normal tone (awake); ASA continuum = minimal sedation.

Number of Participants With an Increase in Clinician-administered Dissociative States Scale (CADSS) Total Score Over Time: DB Treatment Phase

The CADSS used to measure present-state dissociative symptoms, and to assess treatment-emergent dissociative symptoms. It comprises 23 subjective items divided into 3 components: depersonalization (with score range from 0 to 28), derealization (with score range from 0 to 52), and amnesia (with score range from 0 to 8). Participants responses are coded on a 5-point scale (0 = "Not at all", 1 = "Mild", 2 = "Moderate", 3 = 'Severe" and 4 = "Extreme"). The total score is sum of the 23 items and range from 0 to 92, where 0 (best) and 92 (worst). A higher score indicates a more severe condition. Number of participants with an increase in CADSS total score (increase based on maximum CADSS total score change from predose of > 0) was reported.

Full Information

NCT ID

NCT03039192

First Posted

January 31, 2017

Last Updated

October 8, 2020

Sponsor

Janssen Research & Development, LLC

1. Study Identification

Unique Protocol Identification Number

NCT03039192

Brief Title

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

Acronym

Aspire I

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

2. Study Status

Record Verification Date

October 2020

Overall Recruitment Status

Completed

Study Start Date

June 9, 2017 (Actual)

Primary Completion Date

December 18, 2018 (Actual)

Study Completion Date

December 18, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Janssen Research & Development, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Depressive Disorder, Major

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

226 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Esketamine + Standard of care

Arm Type

Experimental

Arm Description

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.

Arm Title

Placebo + Standard of care

Arm Type

Placebo Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Esketamine

Intervention Description

Intranasal esketamine solution 84 milligram (mg)

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Intranasal Placebo solution

Intervention Type

Other

Intervention Name(s)

Standard of Care

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Description

Time Frame

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

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

Baseline and Days 1, 2, 4, 8, 11, 15, 18, 22 and 25

Title

Number of Participants Who Achieved Resolution of Suicidality (CGI-SS-R Score of 0 or 1) Through Double-blind Phase

Description

CGI-SS-R was derived from 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 rating is scored on a 7-point scale from 0 (normal, not at all suicidal) to 6 (among the most extremely suicidal participants). A higher score indicates a more severe condition. Negative change in score indicates improvement. A participant was considered to achieve resolution of suicidality at a given time point if the CGI-SS-R score was 0 (normal, not at all suicidal) or 1 (questionably suicidal).

Time Frame

Days 1, 2, 4, 8, 11, 15, 18, 22 and 25

Title

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

Description

Time Frame

Baseline and Days 1, 2, 4, 8, 11, 15, 18, 22 and 25

Title

Change From Baseline in Beck Hopelessness Scale (BHS) Total Score at Days 8 and 25 During Double-blind Phase

Description

Time Frame

Baseline, Days 8 and 25

Title

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

Description

Time Frame

Baseline and Days 2, 11 and 25

Title

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)

Description

Time Frame

Baseline, Days 2, 11 and 25

Title

Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) at Days 2, 11 and 25 During Double-blind Phase: Sum Score

Description

Time Frame

Baseline, Days 2, 11 and 25

Title

Change From Baseline in Quality of Life in Depression Scale (QLDS) Total Score at Days 2, 11 and 25 During Double-blind Phase

Description

Time Frame

Baseline and Days 2, 11 and 25

Title

Treatment Satisfaction Questionnaire for Medication (TSQM-9) Total Score at Days 15 and 25 During Double-blind Phase

Description

Time Frame

Days 15 and 25

Title

Description

Time Frame

Baseline, Days 1, 2, 4, 8, 11, 15, 18, 22 and 25

Title

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

Description

Time Frame

Baseline and Days 1, 2, 4, 8, 11, 15, 18, 22 and 25

Title

Number of Participants With Treatment Emergent Adverse Events (TEAEs): DB Treatment Phase

Description

Time Frame

Up to Day 25

Title

Number of Participants With Treatment Emergent Abnormal Laboratory Values: DB Treatment Phase

Description

Time Frame

Up to Day 25

Title

Number of Participants With Abnormal Nasal Examinations at Day 25: DB Treatment Phase

Description

Number of participants with abnormal nasal examination were reported. Nasal examination of visual inspection of the epistaxis, nasal crusts, nasal discharge, and nasal erythema was performed.

Time Frame

At Day 25

Title

Number of Participants With Treatment Emergent Abnormal Electrocardiogram (ECG) Values at Any Time: DB Treatment Phase

Description

Time Frame

Up to Day 25

Title

Number of Participants With Abnormal Arterial Oxygen Saturation (SpO2) Levels (Less Than [<] 93%) as Assessed by Pulse Oximetry at Any Time: DB Treatment Phase

Description

Time Frame

Up to Day 25

Title

Number of Participants With Treatment Emergent Vital Signs Abnormalities: DB Treatment Phase

Description

Time Frame

Up to Day 25

Title

Number of Sedated Participants as Assessed by Modified Observer's Assessment of Alertness/Sedation (MOAA/S) Score at Any Time: DB Treatment Phase

Description

Time Frame

Up to Day 25

Title

Number of Participants With an Increase in Clinician-administered Dissociative States Scale (CADSS) Total Score Over Time: DB Treatment Phase

Description

Time Frame

Days 1, 4, 8, 11, 15, 18, 22 and 25

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

64 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Janssen Research & Development, LLC Clinical Trial

Organizational Affiliation

Janssen Research & Development, LLC

Official's Role

Study Director

Facility Information:

Facility Name

UAB Department of Psychiatry and Behavioral Neurobiology

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35294

Country

United States

Facility Name

Metropolitan Neuro Behavioral Institute

City

Chandler

State/Province

Arizona

ZIP/Postal Code

85226

Country

United States

Facility Name

Collaborative NeuroScience Network

City

Garden Grove

State/Province

California

ZIP/Postal Code

92845

Country

United States

Facility Name

Yale University

City

New Haven

State/Province

Connecticut

ZIP/Postal Code

06511

Country

United States

Facility Name

Rush University

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60612

Country

United States

Facility Name

Alexian Behavioral Health Hospital

City

Hoffman Estates

State/Province

Illinois

ZIP/Postal Code

60169

Country

United States

Facility Name

University of Louisville, Department of Psychiatry

City

Louisville

State/Province

Kentucky

ZIP/Postal Code

40202

Country

United States

Facility Name

LSU Health Sciences Center New Orleans

City

New Orleans

State/Province

Louisiana

ZIP/Postal Code

70115

Country

United States

Facility Name

Louisiana Clinical Research

City

Shreveport

State/Province

Louisiana

ZIP/Postal Code

71101

Country

United States

Facility Name

Sheppard Pratt Health System

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21204

Country

United States

Facility Name

CBH Health

City

Gaithersburg

State/Province

Maryland

ZIP/Postal Code

20877

Country

United States

Facility Name

State University of New York

City

Buffalo

State/Province

New York

ZIP/Postal Code

14215

Country

United States

Facility Name

Columbia University Medical Center

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

Facility Name

Clinical Trials of America

City

Hickory

State/Province

North Carolina

ZIP/Postal Code

28601

Country

United States

Facility Name

The Ohio State University

City

Columbus

State/Province

Ohio

ZIP/Postal Code

43210

Country

United States

Facility Name

Medical University of South Carolina

City

Charleston

State/Province

South Carolina

ZIP/Postal Code

29425

Country

United States

Facility Name

University of Texas Southwestern Medical Center

City

Dallas

State/Province

Texas

ZIP/Postal Code

75235

Country

United States

Facility Name

Mental Health Center Prof. Dr. Ivan Temkov

City

Bourgas

ZIP/Postal Code

8001

Country

Bulgaria

Facility Name

Regional Psychiatric Dispansery

City

Bulgaria

ZIP/Postal Code

7003

Country

Bulgaria

Facility Name

State Psychiatric Hospital - Lovech

City

Lovech

ZIP/Postal Code

5500

Country

Bulgaria

Facility Name

UMHAT 'Sveti Georgi'-Plovdiv

City

Plovdiv

ZIP/Postal Code

4002

Country

Bulgaria

Facility Name

Military Medical Academy, Multiprofile Hospital for Active Treatment -Sofia

City

Sofia

ZIP/Postal Code

1606

Country

Bulgaria

Facility Name

North Estonian Medical Centre Foundation

City

Tallinn

ZIP/Postal Code

10614

Country

Estonia

Facility Name

Tartu University Hospital

City

Tartu

ZIP/Postal Code

50417

Country

Estonia

Facility Name

Vivantes Humboldt Klinikum

City

Berlin

ZIP/Postal Code

13509

Country

Germany

Facility Name

Universitatsklinikum Frankfurt

City

Frankfurt Am Main

ZIP/Postal Code

60528

Country

Germany

Facility Name

Klinik für Psychiatrie und Psychotherapie

City

Freiburg

ZIP/Postal Code

79104

Country

Germany

Facility Name

Semmelweis Egyetem Kútvölgyi Klinikai Tömb

City

Budapest

ZIP/Postal Code

1125

Country

Hungary

Facility Name

Szent János Kórház és Észak-budai Egyesített Kórházak

City

Budapest

ZIP/Postal Code

1125

Country

Hungary

Facility Name

Nyírő Gyula Kórház

City

Budapest

ZIP/Postal Code

1135

Country

Hungary

Facility Name

Petz Aladar Megyei Oktato Korhaz

City

Gyor

ZIP/Postal Code

H-9024

Country

Hungary

Facility Name

Pecsi Tudomanyegyetem Klinikai Kozpont

City

Pecs

ZIP/Postal Code

7623

Country

Hungary

Facility Name

Korea University Ansan Hospital

City

Ansan-si

ZIP/Postal Code

15355

Country

Korea, Republic of

Facility Name

Chonnam National University Hospital

City

Gwangju-si

ZIP/Postal Code

61469

Country

Korea, Republic of

Facility Name

Kyung Hee University Medical Center

City

Seoul

ZIP/Postal Code

02447

Country

Korea, Republic of

Facility Name

Samsung Medical Center

City

Seoul

ZIP/Postal Code

06351

Country

Korea, Republic of

Facility Name

Seoul National University Hospital

City

Seoul

ZIP/Postal Code

3080

Country

Korea, Republic of

Facility Name

University Kebangsaan Malaysia Medical Centre

City

Cheras

ZIP/Postal Code

56000

Country

Malaysia

Facility Name

Hospital Kuala Lumpur

City

Kuala Lumpur

ZIP/Postal Code

50586

Country

Malaysia

Facility Name

University Malaya Medical Centre

City

Kuala Lumpur

ZIP/Postal Code

59100

Country

Malaysia

Facility Name

Hospital Tuanku Jaafar

City

Seremban

ZIP/Postal Code

70300

Country

Malaysia

Facility Name

Fakultna nemocnica s poliklinikou v Ziline

City

Zilina

ZIP/Postal Code

012 07

Country

Slovakia

Facility Name

Flexivest 14 Research

City

Cape Town

ZIP/Postal Code

7550

Country

South Africa

Facility Name

Juan Schrönen - Western Cape South Africa

City

Welgemoed

ZIP/Postal Code

7530

Country

South Africa

Facility Name

Hosp. Univ. Fundacion Alcorcon

City

Alcorcón

ZIP/Postal Code

28922

Country

Spain

Facility Name

Hosp. Univ. Vall D'Hebron

City

Barcelona

ZIP/Postal Code

08035

Country

Spain

Facility Name

Hosp. Clinic I Provincial de Barcelona

City

Barcelona

ZIP/Postal Code

08036

Country

Spain

Facility Name

Inst. Internac. Neurociencias Aplicadas

City

Barcelona

ZIP/Postal Code

8006

Country

Spain

Facility Name

Hosp. Univ. de Basurto

City

Bilbao

ZIP/Postal Code

48013

Country

Spain

Facility Name

Hosp. Univ. Ramon Y Cajal

City

Madrid

ZIP/Postal Code

28034

Country

Spain

Facility Name

Clinica Univ. de Navarra

City

Pamplona

ZIP/Postal Code

31008

Country

Spain

Facility Name

Benito Menni Comp. Asist. Salut Mental

City

Sant Boi de Llobregat

ZIP/Postal Code

08830

Country

Spain

Facility Name

Tri-Service Genaral Hospital

City

Neihu District

ZIP/Postal Code

114

Country

Taiwan

Facility Name

Taipei Medical University Shuang Ho Hospital

City

New Taipei City

ZIP/Postal Code

23561

Country

Taiwan

Facility Name

Chung Shan Medical University Hospital

City

Taichung

ZIP/Postal Code

40201

Country

Taiwan

Facility Name

Taipei Veterans General Hospital

City

Taipei

ZIP/Postal Code

11217

Country

Taiwan

12. IPD Sharing Statement

Citations:

PubMed Identifier

35816217

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.

Results Reference

derived

PubMed Identifier

34510411

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.

Results Reference

derived

PubMed Identifier

34412104

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.

Results Reference

derived

PubMed Identifier

32412700

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.

Results Reference

derived

Links:

URL

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=

Description

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)

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