The purpose of this study is to evaluate how well JNJ-54135419 works (efficacy) in addition to comprehensive standard of care (SoC) in rapidly reducing the symptoms of major depressive disorder (MDD, a mental disorder characterized by a persistent feeling of sadness and loss of interest in activities) as compared with psychoactive placebo (does not contain JNJ-54135419) plus SoC in adolescent participants with acute suicidal ideation or behavior.

A Study to Evaluate the Efficacy and Safety of Esketamine for Reduction of Symptoms of Major Depressive Disorder

Depressive Disorder, Major

Major Depressive Disorder With Anxious Distress

Depressive Disorder

Depression

Mood disorders

Brain and Nervous System Conditions

Midazolam

Esketamine

Intranasal Placebo

Oral Placebo

A Double-blind, Randomized, Psychoactive Placebo-controlled Study to Evaluate the Efficacy and Safety of Intranasal Esketamine 84 mg in Addition to Comprehensive Standard of Care for the Rapid Reduction of the Symptoms of Major Depressive Disorder in Adolescent Participants With Acute Suicidal Ideation or Behavior

The CDRS-R is a 17-item, clinician-reported outcome measure of children's depressive symptom severity. Out of the 17-item, 3 items were non-verbal behavior (listless speech, hypoactivity, and depressed affect) rated on a 5 point scale from 1 (no depression) to 5 (severe depression) and 14 items were rated on a 7-point scale from 1 (no depression) to 7 (severe depression), where higher score indicated more severe depression. The CDRS-R total score was the sum of the 17-tems score and it ranged from 17 (normal) to 113 (severe depression). Higher score indicated more severe depression and worse outcome.

The CDRS-R is a 17-item, clinician-reported outcome measure of children's depressive symptom severity. Out of the 17-item, 3 items were non-verbal behavior (listless speech, hypoactivity, and depressed affect) rated on a 5-point scale from 1 (no depression) to 5 (severe depression) and 14 items were rated on a 7-point scale from 1 (no depression) to 7 (severe depression), where higher score indicated more severe depression. The CDRS-R total score was the sum of the 17-tems score and it ranged from 17 (normal) to 113 (severe depression). Higher score indicated more severe depression and worse outcome.

The CGI-SS-R is a single item clinician-rated measure of the severity of participants' suicidality. The CGI-SS-R asks clinicians to rate the severity of a participant's suicidality using a 7-point scale that ranges from 0 (normal, not at all suicidal) to 6 (among the most extremely suicidal patients). Higher scores indicate greater severity.

Remission of depressive symptoms is defined as a CDRS-R total score of both less than or equal to (<=) 28 and <= 34 during the DB treatment phase. The CDRS-R is a 17-item, clinician-reported outcome measure of children's depressive symptom severity. Out of the 17-item, 3 items were non-verbal behavior (listless speech, hypoactivity, and depressed affect) rated on a 5 point scale from 1 (no depression) to 5 (severe depression) and 14 items were rated on a 7-point scale from 1 (no depression) to 7 (severe depression), where higher score indicated more severe depression. The CDRS-R total score was the sum of the 17-tems score and it ranged from 17 (normal) to 113 (severe depression). Higher score indicated more severe depression and worse outcome.

Responders on depressive symptoms is defined as >= 50 percent (%) improvement in CDRS-R total score from baseline during the DB treatment phase. The CDRS-R is a 17-item, clinician-reported outcome measure of children's depressive symptom severity. Out of the 17-item, 3 items were non-verbal behavior (listless speech, hypoactivity, and depressed affect) rated on a 5 point scale from 1 (no depression) to 5 (severe depression) and 14 items were rated on a 7-point scale from 1 (no depression) to 7 (severe depression), where higher score indicated more severe depression. The CDRS-R total score was the sum of the 17-tems score and it ranged from 17 (normal) to 113 (severe depression). Higher score indicated more severe depression and worse outcome.

Participants with resolution of suicidality is defined as a score of 0 (normal, not at all suicidal) or 1 (questionably suicidal) on CGI SS-R, during the DB treatment phase. The CGI-SS-R asks clinicians to rate the severity of a participant's suicidality using a 7-point scale that ranges from 0 (normal, not at all suicidal) to 6 (among the most extremely suicidal patients). Higher score indicate greater severity.

The CGI-SS-R is a single item clinician-rated measure of the severity of participants' suicidality. The CGI-SS-R asks clinicians to rate the severity of a participant's suicidality using a 7-point scale that ranges from 0 (normal, not at all suicidal) to 6 (among the most extremely suicidal patients). Higher score indicate greater severity.

FoST-ClinRO is a clinician-rated measure used to assess a participant's frequency of suicidal thinking assessed during the DB treatment phase. The measure uses a 6-point Likert scale that ranges from 0=Never, to 5=All of the time to assess suicidal thinking frequency, where higher scores indicate a more severe condition.

FoST-PRO is a single item participant reported measure of the frequency of one's suicidal thinking right now. The single item asks participants to rate the frequency with which they have suicidal thoughts (0 = I have no suicidal thoughts, 1 = I have suicidal thoughts a little of the time, 2 = I have suicidal thoughts some of the time, 3 = I have suicidal thoughts most of the time, and 4 = I have suicidal thoughts all of the time). Higher scores indicate greater severity.

The PHQ-A is a modified version of the PHQ-9 scale, specifically designed to measure depressive symptom severity in adolescents. A 10-item version of the PHQ-A will be used in this study; the first 9 items assess depressive symptoms. Adolescents use a 4 point Likert scale to rate the severity of their symptoms over the past 2 weeks (range: 0 = not at all to 3 = nearly every day). The PHQ-A total score is the sum of all item responses. The total score can be used to classify adolescents based on the severity of their depressive symptoms: 0-4 (no or minimal depression), 5-9 (mild depression), 10-14 (moderate depression), 15-19 (moderately severe depression), and 20-27 (severe depression). The tenth PHQ-A item measures the degree to which adolescents experience functional difficulties due to their depressive symptoms. Higher scores indicate greater depressive symptoms.

KIDSCREEN-10 is a global patient-reported outcome (PRO) measure of well-being and health-related quality of life in children and adolescents aged 8-18 years. It includes 10 items that measure the subjective health and psychological, mental and social well-being experiences of children and adolescents over the past week. The scores for the 10 items are summed to produce a total score. This total score can then be transformed into a T-score or percentile rank, based on normative data, to facilitate interpretation. The higher the total score, the better the reported health-related quality of life (HRQoL).

The PGI-S is a single PRO item that captures one's perceptions of the severity of his/her depressive symptoms over the past 24 hours. Participants will be asked to rate their disease severity using the following 5-point scale: 1 = None, 2 = Mild, 3 = Moderate, 4 = Severe, and 5 = Very severe. Higher scores indicate greater disease severity.

The CGI-S provides an overall clinician-determined summary measure of the severity of the participant's illness that considers 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 will be used to rate the overall severity of illness on a scale of 1 to 7. Considering total clinical experience with the depression population, a participant is assessed on severity of illness at the time of rating according to the following scale: 1=normal (not at all ill); 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients. Higher scores indicate greater severity.

Participants will receive intranasal esketamine 84 milligrams (mg) along with oral placebo solution twice weekly for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25). On Day 4 a decrease to intranasal esketamine 56 mg (in a blinded fashion per investigator's judgment) is permitted. Thereafter, dose may be flexed between 56 mg and 84 mg during the treatment period.

Participants will receive oral midazolam (0.0625 milligrams per kilograms [mg/kg]) and intranasal placebo twice weekly for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25). On Day 4 a sham decrease to esketamine 56 mg dose (in a blinded fashion per investigator's judgment) is permitted. Thereafter, sham dose may be flexed between 56 mg and 84 mg during the treatment period.

The purpose of this study is to evaluate how well JNJ-54135419 works (efficacy) in
addition to comprehensive standard of care (SoC) in rapidly reducing the symptoms of
major depressive disorder (MDD, a mental disorder characterized by a persistent feeling
of sadness and loss of interest in activities) as compared with psychoactive placebo
(does not contain JNJ-54135419) plus SoC in adolescent participants with acute suicidal
ideation or behavior.

The CDRS-R is a 17-item, clinician-reported outcome measure of children's depressive
symptom severity. Out of the 17-item, 3 items were non-verbal behavior (listless speech,
hypoactivity, and depressed affect) rated on a 5 point scale from 1 (no depression) to 5
(severe depression) and 14 items were rated on a 7-point scale from 1 (no depression) to
7 (severe depression), where higher score indicated more severe depression. The CDRS-R
total score was the sum of the 17-tems score and it ranged from 17 (normal) to 113
(severe depression). Higher score indicated more severe depression and worse outcome.

The CDRS-R is a 17-item, clinician-reported outcome measure of children's depressive
symptom severity. Out of the 17-item, 3 items were non-verbal behavior (listless speech,
hypoactivity, and depressed affect) rated on a 5-point scale from 1 (no depression) to 5
(severe depression) and 14 items were rated on a 7-point scale from 1 (no depression) to
7 (severe depression), where higher score indicated more severe depression. The CDRS-R
total score was the sum of the 17-tems score and it ranged from 17 (normal) to 113
(severe depression). Higher score indicated more severe depression and worse outcome.

The CGI-SS-R is a single item clinician-rated measure of the severity of participants'
suicidality. The CGI-SS-R asks clinicians to rate the severity of a participant's
suicidality using a 7-point scale that ranges from 0 (normal, not at all suicidal) to 6
(among the most extremely suicidal patients). Higher scores indicate greater severity.

Remission of depressive symptoms is defined as a CDRS-R total score of both less than or
equal to (<=) 28 and <= 34 during the DB treatment phase. The CDRS-R is a 17-item,
clinician-reported outcome measure of children's depressive symptom severity. Out of the
17-item, 3 items were non-verbal behavior (listless speech, hypoactivity, and depressed
affect) rated on a 5 point scale from 1 (no depression) to 5 (severe depression) and 14
items were rated on a 7-point scale from 1 (no depression) to 7 (severe depression),
where higher score indicated more severe depression. The CDRS-R total score was the sum
of the 17-tems score and it ranged from 17 (normal) to 113 (severe depression). Higher
score indicated more severe depression and worse outcome.

Responders on depressive symptoms is defined as >= 50 percent (%) improvement in CDRS-R
total score from baseline during the DB treatment phase. The CDRS-R is a 17-item,
clinician-reported outcome measure of children's depressive symptom severity. Out of the
17-item, 3 items were non-verbal behavior (listless speech, hypoactivity, and depressed
affect) rated on a 5 point scale from 1 (no depression) to 5 (severe depression) and 14
items were rated on a 7-point scale from 1 (no depression) to 7 (severe depression),
where higher score indicated more severe depression. The CDRS-R total score was the sum
of the 17-tems score and it ranged from 17 (normal) to 113 (severe depression). Higher
score indicated more severe depression and worse outcome.

Participants with resolution of suicidality is defined as a score of 0 (normal, not at
all suicidal) or 1 (questionably suicidal) on CGI SS-R, during the DB treatment phase.
The CGI-SS-R asks clinicians to rate the severity of a participant's suicidality using a
7-point scale that ranges from 0 (normal, not at all suicidal) to 6 (among the most
extremely suicidal patients). Higher score indicate greater severity.

The CGI-SS-R is a single item clinician-rated measure of the severity of participants'
suicidality. The CGI-SS-R asks clinicians to rate the severity of a participant's
suicidality using a 7-point scale that ranges from 0 (normal, not at all suicidal) to 6
(among the most extremely suicidal patients). Higher score indicate greater severity.

FoST-ClinRO is a clinician-rated measure used to assess a participant's frequency of
suicidal thinking assessed during the DB treatment phase. The measure uses a 6-point
Likert scale that ranges from 0=Never, to 5=All of the time to assess suicidal thinking
frequency, where higher scores indicate a more severe condition.

FoST-PRO is a single item participant reported measure of the frequency of one's suicidal
thinking right now. The single item asks participants to rate the frequency with which
they have suicidal thoughts (0 = I have no suicidal thoughts, 1 = I have suicidal
thoughts a little of the time, 2 = I have suicidal thoughts some of the time, 3 = I have
suicidal thoughts most of the time, and 4 = I have suicidal thoughts all of the time).
Higher scores indicate greater severity.

The PHQ-A is a modified version of the PHQ-9 scale, specifically designed to measure
depressive symptom severity in adolescents. A 10-item version of the PHQ-A will be used
in this study; the first 9 items assess depressive symptoms. Adolescents use a 4 point
Likert scale to rate the severity of their symptoms over the past 2 weeks (range: 0 = not
at all to 3 = nearly every day). The PHQ-A total score is the sum of all item responses.
The total score can be used to classify adolescents based on the severity of their
depressive symptoms: 0-4 (no or minimal depression), 5-9 (mild depression), 10-14
(moderate depression), 15-19 (moderately severe depression), and 20-27 (severe
depression). The tenth PHQ-A item measures the degree to which adolescents experience
functional difficulties due to their depressive symptoms. Higher scores indicate greater
depressive symptoms.

KIDSCREEN-10 is a global patient-reported outcome (PRO) measure of well-being and
health-related quality of life in children and adolescents aged 8-18 years. It includes
10 items that measure the subjective health and psychological, mental and social
well-being experiences of children and adolescents over the past week. The scores for the
10 items are summed to produce a total score. This total score can then be transformed
into a T-score or percentile rank, based on normative data, to facilitate interpretation.
The higher the total score, the better the reported health-related quality of life
(HRQoL).

The PGI-S is a single PRO item that captures one's perceptions of the severity of his/her
depressive symptoms over the past 24 hours. Participants will be asked to rate their
disease severity using the following 5-point scale: 1 = None, 2 = Mild, 3 = Moderate, 4 =
Severe, and 5 = Very severe. Higher scores indicate greater disease severity.

The CGI-S provides an overall clinician-determined summary measure of the severity of the
participant's illness that considers 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 will be used to rate
the overall severity of illness on a scale of 1 to 7. Considering total clinical
experience with the depression population, a participant is assessed on severity of
illness at the time of rating according to the following scale: 1=normal (not at all
ill); 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill;
7=among the most extremely ill patients. Higher scores indicate greater severity.

Participants will receive intranasal esketamine 84 milligrams (mg) along with oral
placebo solution twice weekly for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25). On Day
4 a decrease to intranasal esketamine 56 mg (in a blinded fashion per investigator's
judgment) is permitted. Thereafter, dose may be flexed between 56 mg and 84 mg during the
treatment period.

Participants will receive oral midazolam (0.0625 milligrams per kilograms [mg/kg]) and
intranasal placebo twice weekly for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25). On
Day 4 a sham decrease to esketamine 56 mg dose (in a blinded fashion per investigator's
judgment) is permitted. Thereafter, sham dose may be flexed between 56 mg and 84 mg
during the treatment period.

A Study to Evaluate the Efficacy and Safety of Esketamine for Reduction of Symptoms of Major Depressive Disorder

Trials at a glance

Trials at a glance

A Study to Evaluate the Efficacy and Safety of Esketamine for Reduction of Symptoms of Major Depressive Disorder

Outcome measures

Primary outcome measures

Secondary outcome measures