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A Study to Evaluate the Efficacy, Pharmacokinetics, Safety and Tolerability of Flexible Doses of Intranasal Esketamine Plus an Oral Antidepressant in Adult Participants With Treatment-resistant Depression

Primary Purpose

Depressive Disorder, Treatment-Resistant

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Esketamine 56 mg

Esketamine 84 mg

Placebo

Duloxetine (Oral Antidepressant)

Escitalopram (Oral Antidepressant)

Sertraline (Oral Antidepressant)

Venlafaxine Extended Release (XR) (Oral Antidepressant)

About this trial

This is an interventional treatment trial for Depressive Disorder, Treatment-Resistant

Eligibility Criteria

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

Inclusion Criteria:

At the start of the screening/prospective observational phase, participant must meet the Diagnostic and Statistical Manual of Mental Disorders-fifth edition (DSM-5) diagnostic criteria for recurrent major depressive disorder (MDD) or single-episode MDD, without psychotic features, based upon clinical assessment and confirmed by the Mini-International Neuropsychiatric Interview (mental status questionnaire) (MINI)
At the start of the screening/prospective observational phase, participant must have had non-response (less than or equal to [<=] 25 percent [%] improvement) to >=1 but <=5 (if current episode is greater than (>) 2 years or not definable, upper limit is applicable to only the last 2 years) oral antidepressant treatments in the current episode of depression, assessed using the Massachusetts General Hospital - Antidepressant Treatment Response Questionnaire (MGH-ATRQ) and confirmed by documented records (for example, medical/ pharmacy/prescription records or letter from a treating physician). In addition, the participant is taking a different oral antidepressant treatment (on the MGH-ATRQ) for at least the previous 2 weeks at or above the minimum therapeutic dose
The participant's current major depressive episode, depression symptom severity (Week 1 Montgomery-Asberg Depression Rating Scale [MADRS] total score >=28 required), and antidepressant treatment response in the current depressive episode, must be confirmed using a Clinical-Validation Inventory for Study Admission (C-VISA)
Participant must be medically stable on the basis of physical examination, medical history, vital signs (including blood pressure), pulse oximetry, and 12-lead electrocardiogram (ECG) performed in the screening/prospective observational phase. If there are any abnormalities that are not specified in the inclusion and exclusion criteria, they must be consistent with the underlying illness in the study population. This determination must be recorded in the participant's source documents and initialed or signed by the investigator
Participant must be medically stable on the basis of clinical laboratory tests performed in the screening/prospective observational phase. If the results of the serum chemistry panel, hematology, or urinalysis are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study. This determination must be recorded in the participant's source documents and initialed or signed by the investigator

Exclusion Criteria:

The participant's depressive symptoms have previously demonstrated non-response to:
1. Esketamine or ketamine in the current major depressive episode per clinical judgment, or
2. All of the oral antidepressant treatment options available in the respective country for the double-blind phase (that is, duloxetine, escitalopram, sertraline, and venlafaxine XR) in the current major depressive episode (based on MGH-ATRQ), or
3. An adequate course of treatment with electroconvulsive therapy (ECT) in the current major depressive episode, defined as at least 7 treatments with unilateral/bilateral ECT
Participant has received vagal nerve stimulation (VNS) or has received deep brain stimulation (DBS) in the current episode of depression
Participant has a current or prior DSM-5 diagnosis of a psychotic disorder or MDD with psychotic features, bipolar or related disorders (confirmed by the MINI), obsessive compulsive disorder (current only), intellectual disability (DSM-5 diagnostic codes 315.8, 317, 318.0, 318.1, 318.2 and 319), autism spectrum disorder, borderline personality disorder, antisocial personality disorder, histrionic personality disorder, or narcissistic personality disorder
Participant has homicidal ideation/intent, per the investigator's clinical judgment, or has suicidal ideation with some intent to act within 6 months prior to the start of the screening/prospective observational phase, per the investigator's clinical judgment or based on the Columbia Suicide Severity Rating Scale (C-SSRS), corresponding to a response of "Yes" on Item 4 (active suicidal ideation with some intent to act, without specific plan) or Item 5 (active suicidal ideation with specific plan and intent) for suicidal ideation on the C-SSRS, or a history of suicidal behavior within the past year prior to the start of the screening/prospective observational phase. Participants reporting suicidal ideation with intent to act or suicidal behavior prior to the start of the double-blind treatment phase should be excluded
Participant has a history of moderate or severe substance or alcohol use disorder according to DSM-5 criteria, except nicotine or caffeine, within 6 months before the start of screening/prospective observational phase a. 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

Atlanta Center for Medical Research
Biomedical Research Foundation of Northwest Louisiana
CBH Health
Adams Clinical
The Medical Research Network, LLC
IPS Research Company
Beijing Anding Hospital of Capital Medical University
Beijing HuiLong Guan Hospital
Peking University Sixth Hospital
The Second People's Hospital of Hunan Province / Brian Hospital of Hunan Province
The second Xiangya Hospital of Central South University
West China Hospital, Sichuan University
Chongqing Mental Health Center
the 3rd Affiliated Hospital,Sun Yansen University
Guangdong Provincial People's Hospital
Hangzhou Seventh People's Hospital
First Hospital, Zhejiang University Medical College
The Second Affiliated Hospital of Zhejiang University
Huzhou third people's Hospital
First Affiliated Hospital of Kunming Medical Unversity
Nanjing Brain Hospital Affilicated to Nanjing Medical University
The First Hospital of Hebei Medical University
Tianjin Anding Hospital
Urumqi fourth Hospital
The first affiliated hospital of Xinjiang medical university
Renmin Hospital of Wuhan Universtiy / Hubei General Hospital
The First Affiliated Hospital of Xi'an Jiaotong University
Xi'an Mental Health Center
Xiamen Xianyue Hospital
The First Affiliated Hospital of Zhengzhou University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Intranasal Esketamine plus Oral Antidepressant

Oral Antidepressant plus Intranasal Placebo

Arm Description

Eligible participants will self-administer esketamine (56 mg or 84 mg) intranasally twice per week for 4 weeks as a flexible dose regimen in the Double-Blind Treatment Phase. All participants will start at a dose of 56 milligram (mg) on Day 1. The dose may be increased to 84 mg or maintained at 56 mg per investigator's discretion. In addition, participants will simultaneously initiate a new, open-label 1 of 4 oral antidepressant medications (duloxetine, escitalopram, sertraline, or venlafaxine extended release [XR]) on Day 1 that will be continued for the duration of the 4-week Double-Blind Treatment Phase.

Eligible Participants will self-administer matching placebo intranasally twice per week for 4 weeks in Double-Blind Treatment Phase. In addition, participants will simultaneously initiate a new, open-label oral antidepressant medications (duloxetine, escitalopram, sertraline, or venlafaxine XR) on Day 1 that will be continued for the duration of Double-Blind Treatment Phase.

Outcomes

Primary Outcome Measures

Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score to the End of Double-blind Treatment Phase (Day 28)

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

Secondary Outcome Measures

Change From Baseline in Depressive Symptoms as Measured by the MADRS Total Score to 24 Hours Post First Dose (Day 2)

Change From Baseline in Sheehan Disability Scale (SDS) Total Score to the End of Double-blind Treatment Phase (Day 28)

The SDS is a subject-reported outcome measure that consists of a 5-item questionnaire which has been widely used and accepted for assessment of functional impairment and associated disability. The first three items assess disruption of (1) work/school, (2) social life, and (3) family life/home responsibilities using a 0-10 rating scale. The score for the first three items are summed to create a total score of 0-30, where a higher score indicates greater impairment. It also has one item on days lost from school or work and one item on days when underproductive.

Percentage of Participants With Onset of Clinical Response

Onset of clinical response is defined as greater than or equal to (>=) 50 percent (%) improvement from baseline in MADRS total score with onset by Day 2 that was maintained through Day 28. The MADRS scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, inability to feel (interest level), pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), summed for a total possible score range of 0 to 60. Higher scores represent a more severe condition. Negative change in score indicates improvement.

Percentage of Responders at the End of Double-blind Treatment Phase (Day 28)

Percentage of responders at the end of double-blind treatment phase (Day 28) were assessed. A participant was defined as a responder at a given time point if the percent improvement from baseline in MADRS total score is at least 50%. The MADRS scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, inability to feel (interest level), pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), summed for a total possible score range of 0 to 60. Higher scores represent a more severe condition. Negative change in score indicates improvement.

Percentage of Participants in Remission at the End of Double-blind Treatment Phase (Day 28)

Percentage of participants in remission at the end of double-blind treatment phase (Day 28) were assessed. A participant was considered as a remitter if participant had a MADRS total score of less than or equal to [<=] 12 at a visit. MADRS scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, inability to feel (interest level), pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), summed for a total possible score range of 0 to 60. Higher scores represent a more severe condition. Negative change in score indicates improvement.

Percentage of Participants With Sustained Remission

Sustained remission is defined as the first occurrence of remission (MADRS Total score <=12) that was maintained through the Day 28 assessment with one excursion prior to Day 28. The MADRS scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, inability to feel (interest level), pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), summed for a total possible score range of 0 to 60. Higher scores represent a more severe condition. Negative change in score indicates improvement.

Change From Baseline in Clinical Global Impression Severity (CGI-S) Scale Score up to the Endpoint (Double-blind Treatment Phase [Day 28])

The CGI-S provides an overall clinician-determined summary measure of the severity of the participant's illness that takes into account all available information, including knowledge of the participant's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the participant's ability to function. The CGI-S evaluates the severity of psychopathology on a scale of 1 to 7. Considering total clinical experience, a participant is assessed on severity of mental illness at the time of rating according to: 1=normal (not at all ill); 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients. The CGI-S permits a global evaluation of the participant's condition at a given time. Negative change in score indicates improvement. The last post-baseline observation during the double-blind phase was carried forward as Endpoint.

Change From Baseline in Generalized Anxiety Disorder 7-item (GAD-7) Scale Score up to the Endpoint (Double-blind Treatment Phase [Day 28])

The GAD-7 is a brief and validated 7-item self-reported assessment of overall anxiety. Participants respond to each item using a 4 point scale with response categories of 0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day. Item responses are summed to yield a total score with a range of 0 to 21, where higher scores indicate more anxiety. The recall period is 2 weeks. The severity of the GAD-7 is categorized as follows: None (0-4), Mild (5-9), Moderate (10-14) and Severe (15-21). The last post-baseline observation during the double-blind phase was carried forward as the "Endpoint".

Change From Baseline in Participant-Reported Health-Related Quality of Life as Assessed by EuroQol-5 Dimension-5 Level (EQ-5D-5L) Score up to the Endpoint (Double-blind Treatment Phase [Day 28]): Health Status Index

The EQ-5D-5L is a standardized 2-part instrument for use as a measure of health outcome, primarily designed for self-completion by respondents. It essentially consists of the EQ-5D-5L descriptive system and the EQ Visual Analogue Scale (EQ-VAS). The EQ-5D-5L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each of the 5 dimensions is divided into 5 levels of perceived problems (Level 1 indicating no problem, Level 2 indicating slight problems, Level 3 indicating moderate problems, Level 4 indicating severe problems, and Level 5 indicating 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. Health Status Index ranges from -0.148 to 0.949, and is anchored at 0 (dead) and 1 (full health), a lower score indicates worse health.

Change From Baseline in Participant-Reported Health Status as Assessed by EuroQol-5 Dimension-5 Level (EQ-5D-5L) Score up to the Endpoint (Double-blind Treatment Phase [Day 28]): Visual Analogue Scale (VAS)

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

Change From Baseline in Participant-Reported Health Status as Assessed by EuroQol-5 Dimension-5 Level (EQ-5D-5L) up to the Endpoint (Double-blind Treatment Phase [Day 28]): Sum Score

EQ-5D-5L consists of EQ-5D-5L descriptive system and EQ visual analogue scale (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 Health Status Index (HSI). HSI ranges from -0.148 to 0.949 and is anchored at 0 (health state value equal to dead) and 1 (full health). EQ-VAS self-rating records the respondent's own assessment of his/her overall health status at time of completion, on a scale of 0 (worst health you can imagine) to 100 (best health you can imagine). Sum score ranges from 0 to 100 where, sum score = (sum of the scores from the 5 dimensions minus 5) *5. Higher score indicates worst health state.

Full Information

NCT ID

NCT03434041

First Posted

February 9, 2018

Last Updated

May 23, 2022

Sponsor

Janssen Research & Development, LLC

1. Study Identification

Unique Protocol Identification Number

NCT03434041

Brief Title

A Study to Evaluate the Efficacy, Pharmacokinetics, Safety and Tolerability of Flexible Doses of Intranasal Esketamine Plus an Oral Antidepressant in Adult Participants With Treatment-resistant Depression

Official Title

A Randomized, Double-blind, Multicenter Active-controlled Study to Evaluate the Efficacy, Pharmacokinetics, Safety and Tolerability of Flexible Doses of Intranasal Esketamine Plus an Oral Antidepressant in Adult Subjects With Treatment-resistant Depression

Study Type

Interventional

2. Study Status

Record Verification Date

May 2022

Overall Recruitment Status

Completed

Study Start Date

May 25, 2018 (Actual)

Primary Completion Date

April 13, 2021 (Actual)

Study Completion Date

April 13, 2021 (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

5. Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy of switching adult participants with treatment-resistant depression (TRD) from a prior antidepressant treatment (to which they have not responded) to flexibly dosed intranasal esketamine (56 milligram [mg] or 84 mg) plus a newly initiated oral antidepressant compared with switching to a newly initiated oral antidepressant (active comparator) plus intranasal placebo, in improving depressive symptoms. Efficacy will be assessed by the change from baseline in the Montgomery Asberg Depression Rating Scale (MADRS) total score from Day 1 (before randomization) to the end of the 4-week double-blind treatment phase.

6. Conditions and Keywords

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

Depressive Disorder, Treatment-Resistant

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

252 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Intranasal Esketamine plus Oral Antidepressant

Arm Type

Experimental

Arm Description

Arm Title

Oral Antidepressant plus Intranasal Placebo

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Esketamine 56 mg

Intervention Description

Participants will self-administer 56 mg of esketamine as intranasal spray.

Intervention Type

Drug

Intervention Name(s)

Esketamine 84 mg

Intervention Description

Participants will self-administer 84 mg of esketamine as intranasal spray.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Participants will self-administer matching placebo as intranasal spray.

Intervention Type

Drug

Intervention Name(s)

Duloxetine (Oral Antidepressant)

Intervention Description

Duloxetine can be selected as the oral antidepressant medication based on investigator's discretion. The minimum therapeutic dose is 60 milligram per day (mg/day).

Intervention Type

Drug

Intervention Name(s)

Escitalopram (Oral Antidepressant)

Intervention Description

Escitalopram can be selected as the oral antidepressant medication based on investigator's discretion. Escitalopram will be started at a dose of 10 mg/day and up-titrated to a maximum dose of 20 mg/day.

Intervention Type

Drug

Intervention Name(s)

Sertraline (Oral Antidepressant)

Intervention Description

Sertraline can be selected as the oral antidepressant medication based on investigator's discretion. Sertraline will be started at a dose of 50 mg/day and up-titrated to a maximum dose of 200 mg/day.

Intervention Type

Drug

Intervention Name(s)

Venlafaxine Extended Release (XR) (Oral Antidepressant)

Intervention Description

Venlafaxine XR can be selected as the oral antidepressant medication based on investigator's discretion. Venlafaxine XR will be started at a dose of 75 mg/day and up-titrated to a maximum dose of 225 mg/day.

Primary Outcome Measure Information:

Title

Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score to the End of Double-blind Treatment Phase (Day 28)

Description

Time Frame

Baseline up to end of the double-blind treatment phase (Day 28)

Secondary Outcome Measure Information:

Title

Change From Baseline in Depressive Symptoms as Measured by the MADRS Total Score to 24 Hours Post First Dose (Day 2)

Description

Time Frame

Baseline (Day 1: predose) to 24 hours post first dose (Day 2)

Title

Change From Baseline in Sheehan Disability Scale (SDS) Total Score to the End of Double-blind Treatment Phase (Day 28)

Description

Time Frame

Baseline up to end of the double-blind treatment phase (Day 28)

Title

Percentage of Participants With Onset of Clinical Response

Description

Time Frame

Day 2 up to Day 28

Title

Percentage of Responders at the End of Double-blind Treatment Phase (Day 28)

Description

Time Frame

Day 28

Title

Percentage of Participants in Remission at the End of Double-blind Treatment Phase (Day 28)

Description

Time Frame

Day 28

Title

Percentage of Participants With Sustained Remission

Description

Time Frame

Up to Day 28

Title

Change From Baseline in Clinical Global Impression Severity (CGI-S) Scale Score up to the Endpoint (Double-blind Treatment Phase [Day 28])

Description

Time Frame

Baseline up to Double-blind Endpoint (Day 28)

Title

Change From Baseline in Generalized Anxiety Disorder 7-item (GAD-7) Scale Score up to the Endpoint (Double-blind Treatment Phase [Day 28])

Description

Time Frame

Baseline up to Endpoint (double-blind treatment phase [Day 28])

Title

Description

Time Frame

Baseline up to Double-blind Endpoint (Day 28)

Title

Description

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

Time Frame

Baseline up to Double-blind Endpoint (Day 28)

Title

Change From Baseline in Participant-Reported Health Status as Assessed by EuroQol-5 Dimension-5 Level (EQ-5D-5L) up to the Endpoint (Double-blind Treatment Phase [Day 28]): Sum Score

Description

Time Frame

Baseline up to Double-blind Endpoint (Day 28)

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: At the start of the screening/prospective observational phase, participant must meet the Diagnostic and Statistical Manual of Mental Disorders-fifth edition (DSM-5) diagnostic criteria for recurrent major depressive disorder (MDD) or single-episode MDD, without psychotic features, based upon clinical assessment and confirmed by the Mini-International Neuropsychiatric Interview (mental status questionnaire) (MINI) At the start of the screening/prospective observational phase, participant must have had non-response (less than or equal to [<=] 25 percent [%] improvement) to >=1 but <=5 (if current episode is greater than (>) 2 years or not definable, upper limit is applicable to only the last 2 years) oral antidepressant treatments in the current episode of depression, assessed using the Massachusetts General Hospital - Antidepressant Treatment Response Questionnaire (MGH-ATRQ) and confirmed by documented records (for example, medical/ pharmacy/prescription records or letter from a treating physician). In addition, the participant is taking a different oral antidepressant treatment (on the MGH-ATRQ) for at least the previous 2 weeks at or above the minimum therapeutic dose The participant's current major depressive episode, depression symptom severity (Week 1 Montgomery-Asberg Depression Rating Scale [MADRS] total score >=28 required), and antidepressant treatment response in the current depressive episode, must be confirmed using a Clinical-Validation Inventory for Study Admission (C-VISA) Participant must be medically stable on the basis of physical examination, medical history, vital signs (including blood pressure), pulse oximetry, and 12-lead electrocardiogram (ECG) performed in the screening/prospective observational phase. If there are any abnormalities that are not specified in the inclusion and exclusion criteria, they must be consistent with the underlying illness in the study population. This determination must be recorded in the participant's source documents and initialed or signed by the investigator Participant must be medically stable on the basis of clinical laboratory tests performed in the screening/prospective observational phase. If the results of the serum chemistry panel, hematology, or urinalysis are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study. This determination must be recorded in the participant's source documents and initialed or signed by the investigator Exclusion Criteria: The participant's depressive symptoms have previously demonstrated non-response to: Esketamine or ketamine in the current major depressive episode per clinical judgment, or All of the oral antidepressant treatment options available in the respective country for the double-blind phase (that is, duloxetine, escitalopram, sertraline, and venlafaxine XR) in the current major depressive episode (based on MGH-ATRQ), or An adequate course of treatment with electroconvulsive therapy (ECT) in the current major depressive episode, defined as at least 7 treatments with unilateral/bilateral ECT Participant has received vagal nerve stimulation (VNS) or has received deep brain stimulation (DBS) in the current episode of depression Participant has a current or prior DSM-5 diagnosis of a psychotic disorder or MDD with psychotic features, bipolar or related disorders (confirmed by the MINI), obsessive compulsive disorder (current only), intellectual disability (DSM-5 diagnostic codes 315.8, 317, 318.0, 318.1, 318.2 and 319), autism spectrum disorder, borderline personality disorder, antisocial personality disorder, histrionic personality disorder, or narcissistic personality disorder Participant has homicidal ideation/intent, per the investigator's clinical judgment, or has suicidal ideation with some intent to act within 6 months prior to the start of the screening/prospective observational phase, per the investigator's clinical judgment or based on the Columbia Suicide Severity Rating Scale (C-SSRS), corresponding to a response of "Yes" on Item 4 (active suicidal ideation with some intent to act, without specific plan) or Item 5 (active suicidal ideation with specific plan and intent) for suicidal ideation on the C-SSRS, or a history of suicidal behavior within the past year prior to the start of the screening/prospective observational phase. Participants reporting suicidal ideation with intent to act or suicidal behavior prior to the start of the double-blind treatment phase should be excluded Participant has a history of moderate or severe substance or alcohol use disorder according to DSM-5 criteria, except nicotine or caffeine, within 6 months before the start of screening/prospective observational phase a. 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

Atlanta Center for Medical Research

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30331

Country

United States

Facility Name

Biomedical Research Foundation of Northwest Louisiana

City

Shreveport

State/Province

Louisiana

ZIP/Postal Code

71104-2136

Country

United States

Facility Name

CBH Health

City

Gaithersburg

State/Province

Maryland

ZIP/Postal Code

20877

Country

United States

Facility Name

Adams Clinical

City

Watertown

State/Province

Massachusetts

ZIP/Postal Code

02472

Country

United States

Facility Name

The Medical Research Network, LLC

City

New York

State/Province

New York

ZIP/Postal Code

10128

Country

United States

Facility Name

IPS Research Company

City

Oklahoma City

State/Province

Oklahoma

ZIP/Postal Code

73106

Country

United States

Facility Name

Beijing Anding Hospital of Capital Medical University

City

Beijing

ZIP/Postal Code

100088Chile

Country

China

Facility Name

Beijing HuiLong Guan Hospital

City

Beijing

ZIP/Postal Code

100096

Country

China

Facility Name

Peking University Sixth Hospital

City

Beijing

ZIP/Postal Code

100191

Country

China

Facility Name

The Second People's Hospital of Hunan Province / Brian Hospital of Hunan Province

City

Changsha

ZIP/Postal Code

410007

Country

China

Facility Name

The second Xiangya Hospital of Central South University

City

Changsha

ZIP/Postal Code

410011

Country

China

Facility Name

West China Hospital, Sichuan University

City

Chengdu

ZIP/Postal Code

610041

Country

China

Facility Name

Chongqing Mental Health Center

City

Chongqing

ZIP/Postal Code

401147

Country

China

Facility Name

the 3rd Affiliated Hospital,Sun Yansen University

City

Guangzhou

ZIP/Postal Code

510000

Country

China

Facility Name

Guangdong Provincial People's Hospital

City

Guangzhou

ZIP/Postal Code

510100

Country

China

Facility Name

Hangzhou Seventh People's Hospital

City

Hangzhou

ZIP/Postal Code

310000

Country

China

Facility Name

First Hospital, Zhejiang University Medical College

City

Hangzhou

ZIP/Postal Code

310003

Country

China

Facility Name

The Second Affiliated Hospital of Zhejiang University

City

Hangzhou

ZIP/Postal Code

310009

Country

China

Facility Name

Huzhou third people's Hospital

City

Hu Zhou

ZIP/Postal Code

313000

Country

China

Facility Name

First Affiliated Hospital of Kunming Medical Unversity

City

Kunming City

ZIP/Postal Code

650032

Country

China

Facility Name

Nanjing Brain Hospital Affilicated to Nanjing Medical University

City

Nanjing

ZIP/Postal Code

210000

Country

China

Facility Name

The First Hospital of Hebei Medical University

City

Shijiazhuang

ZIP/Postal Code

050031

Country

China

Facility Name

Tianjin Anding Hospital

City

Tianjin

ZIP/Postal Code

300222

Country

China

Facility Name

Urumqi fourth Hospital

City

Urumqi

ZIP/Postal Code

830000

Country

China

Facility Name

The first affiliated hospital of Xinjiang medical university

City

Urumqi

ZIP/Postal Code

830054

Country

China

Facility Name

Renmin Hospital of Wuhan Universtiy / Hubei General Hospital

City

Wuhan

ZIP/Postal Code

430060

Country

China

Facility Name

The First Affiliated Hospital of Xi'an Jiaotong University

City

Xi'an

ZIP/Postal Code

710061

Country

China

Facility Name

Xi'an Mental Health Center

City

Xi'an

ZIP/Postal Code

710061

Country

China

Facility Name

Xiamen Xianyue Hospital

City

Xia Men

ZIP/Postal Code

361012

Country

China

Facility Name

The First Affiliated Hospital of Zhengzhou University

City

Zheng Zhou

ZIP/Postal Code

450052

Country

China

12. IPD Sharing Statement

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