Back to results

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 (Aspire II)

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)
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

Sites / Locations

University of California San Diego/Psychiatry
Sharp Mesa Vista Hospital
University of Conneticut School of Medicine
University of Miami Health System
Innovative Clinical Research, Inc.
University of South Florida
Atlanta Behavioral Research, LLC
Memorial Medical Center
Neuroscience Research Institute
Lake Charles Clinical Trials
John Hopkins Hospital
Altea Research Institute
The Zucker Hillside Hospital
Stony Brook University Medical Center
University of North Carolina
University of Cincinnati, Dept of Psychiatry & Behavioral Neuroscience
East Tennessee State University
University of Wisconsin Medical Center
Clínica Privada Banfield S.A
Hospital Fleni
Sanatorio Prof. Leon S. Morra
Clinica Privada de Salud Mental Santa Teresa de Ávila
Medical University Vienna, MUV
Klinikum Wels-Grieskirchen
AZ Sint-Jan Brugge-Oostende AV
UZ Gent
ARIADNE
Hospital Universitario Professor Edgar Santos
Hospital Das Clinicas Da Universidade Federal De Minas Gerais
Universidade Federal Do Ceara
Instituto Bairral de Psiquiatria
CEMEC - Centro Multidisciplinar de Estudos Clínicos
Instituto de Psiquiatria - Hcfmusp
St. Michael's Hospital
Institut universitaire en sante mentale de Montreal
Fakultni nemocnice Brno
Nemocnice s pol. Havirov, p.o.
Narodni ustav dusevniho zdravi
Vseobecna Fakultní Nemocnice
Úst?ední vojenské nemocnice Praha
Hôpital de Bohars
CHRU Montpellier - Hôpital Lapeyronie
CHU Caremeau
Hopital Sainte Anne
CHU Saint-Etienne - Hôpital Nord
CHU Toulouse
Republic Kaunas Hospital
Hospital of Lithuanian University of Health Sciences Kaunas Clinics
Vilnius Mental Health Center
Uniwersyteckie Centrum Kliniczne
Szpital Specjalistyczny im. H. Klimontowicza, Oddzial Psychiatryczny
SPZOZ CSK UM w Lodzi Klinika Zaburzen Afektywnych i Psychotycznych
Klinika Psychiatryczna WUM Mazowieckie Specjalistyczne Centrum Zdrowia im prof Jana Mazurkiewicza
Hosp. Univ. Vall D Hebron
Inst. Internac. Neurociencias Aplicadas
Hosp. Univ. de Basurto
Clinica Univ. de Navarra
Bursa Sevket Yilmaz Research and Training Hospital
Uludag University Medical Faculty
Şişli Etfal Research Training Hospital
Samsun Psychiatric 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) on Day 1, 4, 8, 11, 15, 18, 22, and 25 along with standard of care antidepressant treatment.

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

Outcomes

Primary Outcome Measures

Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at 24 Hours Post First Dose (Last Observation Carried Forward [LOCF] Data): Double-blind (DB) Treatment 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.

Change From Baseline in Clinical Global Impression-Severity of Suicidality - Revised (CGI-SS-R) Scale at 24 Hours Post First Dose (LOCF Data): DB Treatment Phase

Clinical global impression-severity of suicidality-revised (CGI-SS-R) scale is revised version of 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 summarizes the clinician's overall impression of severity of suicidality on a 7-point scale from 0 (normal, not at all suicidal) to 6 (among the most extremely suicidal participants), based on the totality of information available to the clinician. Higher score indicates a more severe condition. Negative change in score indicates improvement.

Secondary Outcome Measures

Number of Participants With Remission of Major Depressive Disorder (MADRS Total Score Less Than or Equal to [<=] 12): DB Treatment Phase

Change From Baseline in MADRS Total Score at 4 Hours Post First Dose at Day 1 (4 Hours Post First Dose), and 2, 4, 8, 11, 15, 18, 22 and 25: DB Treatment Phase

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

Change From Baseline in CGI-SS-R Score at 4 Hours Post First Dose at Day 1 (4 Hours Post First Dose), and 2, 4, 8, 11, 15, 18, 22 and 25: DB Treatment Phase

Number of Participants Who Achieved Resolution of Suicidality (CGI-SS-R Score of 0 or 1): DB Treatment Phase

CGI-SS-R is revised version of the CGI-S. The CGI-SS-R summarizes the clinician's overall impression of severity of suicidality on a 7-point scale from 0 (normal, not at all suicidal) to 6 (among the most extremely suicidal participants), based on the totality of information available to the clinician. Higher score indicates a more severe condition. A participant was considered to have achieved 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). Participants who did not met such criterion or discontinued prior to the time point for any reason were not considered to have resolution of suicidality.

Change From Baseline in Clinical Global Impression of Imminent Suicide Risk (CGI-SR-I) at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25: DB Treatment 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 in DB Treatment 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 European Quality of Life Group, 5-Dimension, 5-Level (EQ-5D-5L) Sum Score at Days 2, 11 and 25 of the DB Treatment Phase

EQ-5D-5L consists of EQ-5D-5L descriptive system and EQ visual analogue scale (EQ-VAS). EQ-5D-5L descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each has 5 levels of perceived problems (no problem, slight, moderate, severe and extreme problems). Participant selects answer for each of 5 dimensions considering response that best matches his/her health "today". Responses were used to generate Health Status Index (HSI). HSI ranges from 0 (dead) to 1.00 (full health). EQ-VAS self-rating records respondent's own assessment of his/her overall health status at time of completion, on a scale of 0 (worst imaginable health)-100 (best imaginable health). Sum score ranges from 0 -100. Sum score=(sum of the scores from the 5 dimensions minus 5)*5. Higher score indicates worse health state. Negative change in score indicates improvement.

Change From Baseline in European Quality of Life Group, Visual Analogue Scale (EQ-VAS) Score at Days 2, 11 and 25 of the DB Treatment Phase

EQ-5D-5L is a 2-part instrument for use as a measure of health outcome, designed for self-completion by respondents. It consists of EQ-5D-5L descriptive system and EQ VAS. The EQ VAS self-rating records the respondent's own assessment of his or her overall health status at the time of completion, on a scale of 0 (the worst health you can imagine) to 100 (the best health you can imagine). Positive change in score indicates improvement.

Change From Baseline in EQ-5D-5L Health Status Index at Days 2, 11 and 25 of the DB Treatment Phase

EQ-5D-5L is a 2-part instrument for use as a measure of health outcome, designed for self-completion by respondents. It consists of EQ-5D-5L descriptive system and EQ VAS. EQ-5D-5L descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each has 5 levels of perceived problems (1-no problem, 2-slight problems, 3-moderate problems, 4-severe problems, 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 HSI. HSI ranges from 0 (dead) to 1.00 (full health). Positive change in score indicates improvement.

Change From Baseline in Quality of Life in Depression Scale (QLDS) Total Score at Days 2, 11 and 25 of the DB Treatment Phase

The QLDS is a disease-specific patient-reported outcome designed to assess health-related quality of life in patients with MDD, it captures the impact of depression and its treatment from the participant's perspective. The instrument has a recall period of "at the moment" and contains 34 items with "true"/"not true" response options. 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) Domain Score at Days 15 and 25: DB Treatment 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 (Participant-Reported Frequency of Suicidal Thinking) Score at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25: DB Treatment 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).

Change From Baseline in Suicide Ideation and Behavior Assessment Tool (SIBAT) Module 7 (Clinician-rated Frequency of Suicidal Thinking [FoST]) Score at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25: DB Treatment 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 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

NCT03097133

First Posted

March 27, 2017

Last Updated

August 26, 2021

Sponsor

Janssen Research & Development, LLC

1. Study Identification

Unique Protocol Identification Number

NCT03097133

Brief Title

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

Acronym

Aspire II

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

August 2021

Overall Recruitment Status

Completed

Study Start Date

June 15, 2017 (Actual)

Primary Completion Date

April 11, 2019 (Actual)

Study Completion Date

April 11, 2019 (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 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.

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

230 (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) on Day 1, 4, 8, 11, 15, 18, 22, and 25 along with standard of care antidepressant treatment.

Arm Title

Placebo + Standard of care

Arm Type

Placebo Comparator

Arm Description

Participants will receive intranasal placebo on Day 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

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

Intervention Name(s)

Placebo

Intervention Description

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

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 the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at 24 Hours Post First Dose (Last Observation Carried Forward [LOCF] Data): Double-blind (DB) Treatment Phase

Description

Time Frame

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

Title

Change From Baseline in Clinical Global Impression-Severity of Suicidality - Revised (CGI-SS-R) Scale at 24 Hours Post First Dose (LOCF Data): DB Treatment Phase

Description

Time Frame

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

Secondary Outcome Measure Information:

Title

Number of Participants With Remission of Major Depressive Disorder (MADRS Total Score Less Than or Equal to [<=] 12): DB Treatment Phase

Description

Time Frame

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

Title

Change From Baseline in MADRS Total Score at 4 Hours Post First Dose at Day 1 (4 Hours Post First Dose), and 2, 4, 8, 11, 15, 18, 22 and 25: DB Treatment Phase

Description

Time Frame

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

Title

Change From Baseline in CGI-SS-R Score at 4 Hours Post First Dose at Day 1 (4 Hours Post First Dose), and 2, 4, 8, 11, 15, 18, 22 and 25: DB Treatment Phase

Description

Time Frame

Baseline (Day 1, predose), Days 1 (4 hours postdose), 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): DB Treatment Phase

Description

Time Frame

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

Title

Change From Baseline in Clinical Global Impression of Imminent Suicide Risk (CGI-SR-I) at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25: DB Treatment Phase

Description

Time Frame

Baseline (Day 1, predose), Days 1 (4 hours postdose), 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 in DB Treatment Phase

Description

Time Frame

Baseline, Days 8 and 25

Title

Change From Baseline in European Quality of Life Group, 5-Dimension, 5-Level (EQ-5D-5L) Sum Score at Days 2, 11 and 25 of the DB Treatment Phase

Description

Time Frame

Baseline, Days 2, 11 and 25

Title

Change From Baseline in European Quality of Life Group, Visual Analogue Scale (EQ-VAS) Score at Days 2, 11 and 25 of the DB Treatment Phase

Description

Time Frame

Baseline, Days 2, 11 and 25

Title

Change From Baseline in EQ-5D-5L Health Status Index at Days 2, 11 and 25 of the DB Treatment Phase

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 of the DB Treatment Phase

Description

Time Frame

Baseline, Days 2, 11 and 25

Title

Treatment Satisfaction Questionnaire for Medication (TSQM-9) Domain Score at Days 15 and 25: DB Treatment Phase

Description

Time Frame

Days 15 and 25

Title

Description

Time Frame

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

Title

Description

Time Frame

Baseline, Days 1 (4 hours postdose), 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) 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

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

University of California San Diego/Psychiatry

City

San Diego

State/Province

California

ZIP/Postal Code

92103-8229

Country

United States

Facility Name

Sharp Mesa Vista Hospital

City

San Diego

State/Province

California

ZIP/Postal Code

92123

Country

United States

Facility Name

University of Conneticut School of Medicine

City

Farmington

State/Province

Connecticut

ZIP/Postal Code

06030

Country

United States

Facility Name

University of Miami Health System

City

Miami

State/Province

Florida

ZIP/Postal Code

33136

Country

United States

Facility Name

Innovative Clinical Research, Inc.

City

North Miami

State/Province

Florida

ZIP/Postal Code

33161

Country

United States

Facility Name

University of South Florida

City

Tampa

State/Province

Florida

ZIP/Postal Code

33613

Country

United States

Facility Name

Atlanta Behavioral Research, LLC

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30338

Country

United States

Facility Name

Memorial Medical Center

City

Springfield

State/Province

Illinois

ZIP/Postal Code

62702

Country

United States

Facility Name

Neuroscience Research Institute

City

Winfield

State/Province

Illinois

ZIP/Postal Code

60190

Country

United States

Facility Name

Lake Charles Clinical Trials

City

Lake Charles

State/Province

Louisiana

ZIP/Postal Code

70629

Country

United States

Facility Name

John Hopkins Hospital

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21287

Country

United States

Facility Name

Altea Research Institute

City

Las Vegas

State/Province

Nevada

ZIP/Postal Code

89102

Country

United States

Facility Name

The Zucker Hillside Hospital

City

Glen Oaks

State/Province

New York

ZIP/Postal Code

11004

Country

United States

Facility Name

Stony Brook University Medical Center

City

Stony Brook

State/Province

New York

ZIP/Postal Code

11794

Country

United States

Facility Name

University of North Carolina

City

Chapel Hill

State/Province

North Carolina

ZIP/Postal Code

27599

Country

United States

Facility Name

University of Cincinnati, Dept of Psychiatry & Behavioral Neuroscience

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45219

Country

United States

Facility Name

East Tennessee State University

City

Johnson City

State/Province

Tennessee

ZIP/Postal Code

37604

Country

United States

Facility Name

University of Wisconsin Medical Center

City

Madison

State/Province

Wisconsin

ZIP/Postal Code

53705

Country

United States

Facility Name

Clínica Privada Banfield S.A

City

Banfield

ZIP/Postal Code

B1828CKR

Country

Argentina

Facility Name

Hospital Fleni

City

Ciudad de Buenos Aires

ZIP/Postal Code

C1428AQK

Country

Argentina

Facility Name

Sanatorio Prof. Leon S. Morra

City

Cordoba

ZIP/Postal Code

X5009BIN

Country

Argentina

Facility Name

Clinica Privada de Salud Mental Santa Teresa de Ávila

City

La Plata

ZIP/Postal Code

B1904ADM

Country

Argentina

Facility Name

Medical University Vienna, MUV

City

Vienna

ZIP/Postal Code

1090

Country

Austria

Facility Name

Klinikum Wels-Grieskirchen

City

Wels

ZIP/Postal Code

4600

Country

Austria

Facility Name

AZ Sint-Jan Brugge-Oostende AV

City

Brugge

ZIP/Postal Code

8000

Country

Belgium

Facility Name

UZ Gent

City

Gent

ZIP/Postal Code

9000

Country

Belgium

Facility Name

ARIADNE

City

Lede

ZIP/Postal Code

9340

Country

Belgium

Facility Name

Hospital Universitario Professor Edgar Santos

City

Bahia

ZIP/Postal Code

40110-060

Country

Brazil

Facility Name

Hospital Das Clinicas Da Universidade Federal De Minas Gerais

City

Belo Horizonte

ZIP/Postal Code

301301

Country

Brazil

Facility Name

Universidade Federal Do Ceara

City

Fortaleza

ZIP/Postal Code

60430-370

Country

Brazil

Facility Name

Instituto Bairral de Psiquiatria

City

Itapira

ZIP/Postal Code

13970-905

Country

Brazil

Facility Name

CEMEC - Centro Multidisciplinar de Estudos Clínicos

City

Santo Andre

ZIP/Postal Code

09190-510

Country

Brazil

Facility Name

Instituto de Psiquiatria - Hcfmusp

City

Sao Paulo

ZIP/Postal Code

05403-903

Country

Brazil

Facility Name

St. Michael's Hospital

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5B 1W8

Country

Canada

Facility Name

Institut universitaire en sante mentale de Montreal

City

Montréal

State/Province

Quebec

ZIP/Postal Code

H1N 3M5

Country

Canada

Facility Name

Fakultni nemocnice Brno

City

Brno

ZIP/Postal Code

62500

Country

Czechia

Facility Name

Nemocnice s pol. Havirov, p.o.

City

Havirov

ZIP/Postal Code

73601

Country

Czechia

Facility Name

Narodni ustav dusevniho zdravi

City

Klecany

ZIP/Postal Code

25067

Country

Czechia

Facility Name

Vseobecna Fakultní Nemocnice

City

Praha

ZIP/Postal Code

12000

Country

Czechia

Facility Name

Úst?ední vojenské nemocnice Praha

City

Praha

ZIP/Postal Code

16902

Country

Czechia

Facility Name

Hôpital de Bohars

City

Bohars

ZIP/Postal Code

29820

Country

France

Facility Name

CHRU Montpellier - Hôpital Lapeyronie

City

Montpellier

ZIP/Postal Code

34090

Country

France

Facility Name

CHU Caremeau

City

Nimes

ZIP/Postal Code

30029

Country

France

Facility Name

Hopital Sainte Anne

City

Paris

ZIP/Postal Code

75014

Country

France

Facility Name

CHU Saint-Etienne - Hôpital Nord

City

Saint-Priest en Jarez

ZIP/Postal Code

42270

Country

France

Facility Name

CHU Toulouse

City

Toulouse

ZIP/Postal Code

31059

Country

France

Facility Name

Republic Kaunas Hospital

City

Kaunas County

Country

Lithuania

Facility Name

Hospital of Lithuanian University of Health Sciences Kaunas Clinics

City

Kaunas

ZIP/Postal Code

LT-50009

Country

Lithuania

Facility Name

Vilnius Mental Health Center

City

Vilnius

ZIP/Postal Code

10309

Country

Lithuania

Facility Name

Uniwersyteckie Centrum Kliniczne

City

Gdansk

ZIP/Postal Code

80-952

Country

Poland

Facility Name

Szpital Specjalistyczny im. H. Klimontowicza, Oddzial Psychiatryczny

City

Gorlice

ZIP/Postal Code

38-300

Country

Poland

Facility Name

SPZOZ CSK UM w Lodzi Klinika Zaburzen Afektywnych i Psychotycznych

City

Lodz

ZIP/Postal Code

92-216

Country

Poland

Facility Name

Klinika Psychiatryczna WUM Mazowieckie Specjalistyczne Centrum Zdrowia im prof Jana Mazurkiewicza

City

Pruszkow

ZIP/Postal Code

05-802

Country

Poland

Facility Name

Hosp. Univ. Vall D Hebron

City

Barcelona

ZIP/Postal Code

08035

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

Clinica Univ. de Navarra

City

Pamplona

ZIP/Postal Code

31008

Country

Spain

Facility Name

Bursa Sevket Yilmaz Research and Training Hospital

City

Bursa

ZIP/Postal Code

16240

Country

Turkey

Facility Name

Uludag University Medical Faculty

City

Bursa

ZIP/Postal Code

16285

Country

Turkey

Facility Name

Şişli Etfal Research Training Hospital

City

Istanbul

ZIP/Postal Code

34360

Country

Turkey

Facility Name

Samsun Psychiatric Hospital

City

Samsun

ZIP/Postal Code

55070

Country

Turkey

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

32861217

Citation

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.

Results Reference

derived

Links:

URL

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=

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 II)

Learn more about this trial

We'll reach out to this number within 24 hrs