Trial · NCT04338321
A Long-term Comparison of Esketamine Nasal Spray Versus Quetiapine Extended Release, Both in Combination With a Selective Serotonin Reuptake Inhibitor/Serotonin-Norepinephrine Reuptake Inhibitor, in Participants With Treatment Resistant Major Depressive Disorder
NCT04338321, Phase 3, Completed, Janssen-Cilag International NV; results first posted 2023-02-15
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. A Long-term Comparison of Esketamine Nasal Spray Versus Quetiapine Extended Release, Both in Combination With a Selective Serotonin Reuptake Inhibitor/Serotonin-Norepinephrine Reuptake Inhibitor, in Participants With Treatment Resistant Major Depressive Disorder. Trials, record NCT04338321. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT04338321
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
A Long-term Comparison of Esketamine Nasal Spray Versus Quetiapine Extended Release, Both in Combination With a Selective Serotonin Reuptake Inhibitor/Serotonin-Norepinephrine Reuptake Inhibitor, in Participants With Treatment Resistant Major Depressive Disorder
- NCT number
- NCT04338321
- Status
- Completed
- Phases
- Phase 3
- Enrollment
- 676 participants, actual
- Lead sponsor
- Janssen-Cilag International NV
- Conditions
- Depressive Disorder, Major
- Interventions
- Esketamine 28 mg, Esketamine 56 mg, Esketamine 84 mg, Quetiapine XR 50 mg, Quetiapine XR 100 mg, Quetiapine XR 150 mg, SSRI/SNRI
- First posted
- 2020-04-08
- Last updated
- 2025-04-29
- Other registries' IDs
- eudract:2019-002992-33
- Results first posted
- 2023-02-15
- Limitations and caveats
To minimize potential bias, the Montgomery-Asberg Depression Rating Scale (MADRS) was performed by an independent on-site rater who was blinded to the participant's treatment, and who was not involved in any other study assessments or treatment decisions.
Source ClinicalTrials.gov
Registered outcomes25
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Percentage of Participants With Remission as Assessed by the Montgomery-Asberg Depression Rating Scale (MADRS) Score at Week 8 | Week 8 | Percentage of participants with remission as assessed by the MADRS at Week 8 was reported. The MADRS is a clinician-rated scale designed to measure depression severity and to detect changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition. The MADRS evaluates apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts. A participant was defined as being in remission if the MADRS total score was less than or equal to (\<=)10 and no treatment or study discontinuation before Week 8. |
| Secondary | Percentage of Participants With Both Remission at Week 8 and Relapse-free Until Week 32 | Week 32 | Percentage of participants with both remission at Week 8 and relapse-free until Week 32 were reported. A participant was defined as being in remission if the MADRS total score was \<= 10 and no treatment or study discontinuation before Week 8. A relapse was defined by any of following: a) Worsening of depressive symptoms as indicated by MADRS total score greater than or equal to (\>=) 22 confirmed by 1 additional assessment of MADRS total score \>= 22 within the next 5 to 15 days. The date of the second MADRS assessment was used for the date of relapse; b) Any psychiatric hospitalization for: worsening of depression, suicide prevention or suicide attempt, the start date of hospitalization was the date of relapse; c) Suicide attempt, completed suicide, or any other clinically relevant event determined by investigator's judgment to be indicative of a relapse of depressive illness, but without hospitalized. The onset of the event was used for the date of relapse. |
| Secondary | Change From Baseline in Clinician-rated Overall MADRS Score | Baseline, Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32 | Change from baseline in clinician-rated overall MADRS score was reported. The MADRS is a clinician-rated scale designed to measure depression severity and to detect changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of the symptoms), summed up for a total possible score range of 0 to 60. Higher scores represent a more severe condition. The MADRS evaluates apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts. |
| Secondary | Change From Baseline in Clinician-rated Overall MADRS Score at Last Observation Carried Forward (LOCF) | Baseline, LOCF at Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32 | Change from baseline in clinician-rated overall MADRS score at LOCF was reported. The MADRS is a clinician-rated scale designed to measure depression severity and to detect changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of the symptoms), summed up for a total possible score range of 0 to 60. Higher scores represent a more severe condition. The MADRS evaluates apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts. LOCF is defined as the participants who had a missing value or who stopped treatment at a specific time point had their last non-missing value carried forward. |
| Secondary | Change From Baseline in Clinician-rated Overall Severity of Depressive Illness as Assessed by Clinical Global Impression - Severity (CGI-S) Scale Score | Baseline, Weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 28, 32 | Change from baseline in clinician-rated overall severity of depressive illness as assessed by CGI-S scale score was reported. 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 participants. Negative change in score indicates improvement. |
| Secondary | Change From Baseline in Clinician-rated Overall Severity of Depressive Illness as Assessed by CGI-S Scale Score at LOCF | Baseline, LOCF at Weeks 2, 3, 4, 8, 12, 16, 20, 24, 28, 32 | Change from Baseline in clinician-rated overall severity of depressive illness as assessed by CGI-S scale score at LOCF was reported. 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. 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 participants. LOCF is defined as the participants who had a missing value or who stopped treatment at a specific time point had their last non-missing value carried forward. |
| Secondary | Clinician-rated Overall Severity of Depressive Illness as Assessed by Clinical Global Impression - Change (CGI-C) Scale Score | Baseline, Weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 28, 32 | Clinician-rated overall severity of depressive illness as assessed by CGI-C scale score was reported. The CGI-C evaluates the total improvement whether or not entirely due to drug treatment on a scale of 1 to 7. Compared to the condition at baseline, a participant is assessed on how much he/she has changed, according to: 1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; 7 = very much worse. Higher scores indicate more severity. |
| Secondary | Number of Participants With Clinician-rated Overall Severity of Depressive Illness as Assessed by CGI-C Scale Score at LOCF | Baseline, LOCF at Weeks 2, 3, 4, 8, 12, 16, 20, 24, 28, 32 | Number of participants with clinician-rated overall severity of depressive illness as assessed by CGI-C scale score at LOCF was reported. The CGI-C evaluates the total improvement whether or not entirely due to drug treatment on a scale of 1 to 7. Compared to the condition at baseline, a participant is assessed on how much he/she has changed, according to: 1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; 7 = very much worse. Higher scores indicate more severity. LOCF is defined as the participants who had a missing value or who stopped treatment at a specific time point had their last non-missing value carried forward. |
| Secondary | Change From Baseline in Participant-reported Depressive Symptoms as Assessed by Patient Health Questionnaire (PHQ) 9-item Total Score | Baseline, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32 | Change from baseline in participant-reported depressive symptoms as assessed by PHQ 9-item total score was reported. The PHQ-9 is a validated 9-item, patient-reported outcome (PRO) measure to assess depressive symptoms. Each item is rated on a 4-point scale (0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day). The participant's item responses are summed to provide a total score (range of 0 to 27), with higher scores indicating greater severity of depressive symptoms. The severity of the PHQ-9 is categorized as follows: None-minimal (0-4), Mild (5-9), Moderate (10-14), Moderately Severe (15-19) and Severe (20-27). |
| Secondary | Change From Baseline in Participant-reported Depressive Symptoms as Assessed by PHQ 9-item Total Score at LOCF | Baseline, LOCF at Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32 | Change from baseline in participant-reported depressive symptoms as assessed by PHQ 9-item total score at LOCF was reported. The PHQ-9 is a validated 9-item, PRO measure to assess depressive symptoms. Each item is rated on a 4-point scale (0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day). The participant's item responses are summed to provide a total score (range of 0 to 27), with higher scores indicating greater severity of depressive symptoms. The severity of the PHQ-9 is categorized as follows: None-minimal (0-4), Mild (5-9), Moderate (10-14), Moderately Severe (15-19) and Severe (20-27). LOCF is defined as participants who had a missing value or who stopped treatment at a specific time point had their last non-missing value carried forward. |
1 to 10 of 25Source ClinicalTrials.gov
See all 25 registered outcomesOutcomes25
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Percentage of Participants With Remission as Assessed by the Montgomery-Asberg Depression Rating Scale (MADRS) Score at Week 8 | Week 8 | The full analysis set (FAS) included all randomized participants. | Percentage of participants | NUMBER |
| SECONDARY | Percentage of Participants With Both Remission at Week 8 and Relapse-free Until Week 32 | Week 32 | The FAS includes all randomized participants. | Percentage of Participants | NUMBER |
| SECONDARY | Change From Baseline in Clinician-rated Overall MADRS Score | Baseline, Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32 | The FAS included all randomized participants. Here, 'N' (number of participants analyzed) signifies participants evaluable for this outcome measure. Here, 'n' (number analyzed) signifies participants evaluable for this outcome measure at specified time points. | Unit on scale | MEAN |
| SECONDARY | Change From Baseline in Clinician-rated Overall MADRS Score at Last Observation Carried Forward (LOCF) | Baseline, LOCF at Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32 | The FAS included all randomized participants. Here, 'N' (number of participants analyzed) signifies participants evaluable for this outcome measure. | Unit on scale | MEAN |
| SECONDARY | Change From Baseline in Clinician-rated Overall Severity of Depressive Illness as Assessed by Clinical Global Impression - Severity (CGI-S) Scale Score | Baseline, Weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 28, 32 | The FAS included all randomized participants. Here, 'N' (number of participants analyzed) signifies participants evaluable for this outcome measure. Here, 'n' (number analyzed) signifies participants evaluable for this outcome measure at specified time points. | Units on scale | MEAN |
| SECONDARY | Change From Baseline in Clinician-rated Overall Severity of Depressive Illness as Assessed by CGI-S Scale Score at LOCF | Baseline, LOCF at Weeks 2, 3, 4, 8, 12, 16, 20, 24, 28, 32 | The FAS included all randomized participants. Here, 'N' (number of participants analyzed) signifies participants evaluable for this outcome measure. | Units on scale | MEAN |
| SECONDARY | Clinician-rated Overall Severity of Depressive Illness as Assessed by Clinical Global Impression - Change (CGI-C) Scale Score | Baseline, Weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 28, 32 | The FAS included all randomized participants. Here, 'N' (number of participants analyzed) signifies participants evaluable for this outcome measure. Here, 'n' (number analyzed) signifies participants evaluable for this outcome measure at specified time points. | Units on scale | MEAN |
| SECONDARY | Number of Participants With Clinician-rated Overall Severity of Depressive Illness as Assessed by CGI-C Scale Score at LOCF | Baseline, LOCF at Weeks 2, 3, 4, 8, 12, 16, 20, 24, 28, 32 | The FAS included all randomized participants. Here, 'N' (number of participants analyzed) signifies participants evaluable for this outcome measure. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Change From Baseline in Participant-reported Depressive Symptoms as Assessed by Patient Health Questionnaire (PHQ) 9-item Total Score | Baseline, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32 | The FAS included all randomized participants. Here, 'N' (number of participants analyzed) signifies participants evaluable for this outcome measure. Here, 'n' (number analyzed) signifies participants evaluable for this outcome measure at specified time points. | Units on scale | MEAN |
| SECONDARY | Change From Baseline in Participant-reported Depressive Symptoms as Assessed by PHQ 9-item Total Score at LOCF | Baseline, LOCF at Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32 | The FAS included all randomized participants. Here, 'N' (number of participants analyzed) signifies participants evaluable for this outcome measure. Here, 'n' (number analyzed) signifies participants evaluable for this outcome measure at specified time points. | Units on scale | MEAN |
1 to 10 of 25Source ClinicalTrials.gov
See all 25 outcomesResults by group882
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Percentage of Participants With Remission as Assessed by the Montgomery-Asberg Depression Rating Scale (MADRS) Score at Week 8 | Esketamine Nasal Spray + Oral Antidepressant (AD) | 27.1 | Percentage of participants | ||
| Percentage of Participants With Remission as Assessed by the Montgomery-Asberg Depression Rating Scale (MADRS) Score at Week 8 | Quetiapine Extended Release (XR) + Oral AD | 17.6 | Percentage of participants | ||
| Percentage of Participants With Both Remission at Week 8 and Relapse-free Until Week 32 | Esketamine Nasal Spray + Oral Antidepressant (AD) | 21.7 | Percentage of Participants | ||
| Percentage of Participants With Both Remission at Week 8 and Relapse-free Until Week 32 | Quetiapine Extended Release (XR) + Oral AD | 14.1 | Percentage of Participants | ||
| Change From Baseline in Clinician-rated Overall MADRS Score | Esketamine Nasal Spray + Oral Antidepressant (AD) | Week 1 | -5.3 | Standard Deviation 5.71 | Unit on scale |
| Change From Baseline in Clinician-rated Overall MADRS Score | Quetiapine Extended Release (XR) + Oral AD | Week 1 | -3.7 | Standard Deviation 4.65 | Unit on scale |
| Change From Baseline in Clinician-rated Overall MADRS Score | Esketamine Nasal Spray + Oral Antidepressant (AD) | Week 2 | -9.0 | Standard Deviation 6.87 | Unit on scale |
| Change From Baseline in Clinician-rated Overall MADRS Score | Quetiapine Extended Release (XR) + Oral AD | Week 2 | -6.1 | Standard Deviation 6.52 | Unit on scale |
| Change From Baseline in Clinician-rated Overall MADRS Score | Esketamine Nasal Spray + Oral Antidepressant (AD) | Week 4 | -12.8 | Standard Deviation 7.50 | Unit on scale |
| Change From Baseline in Clinician-rated Overall MADRS Score | Quetiapine Extended Release (XR) + Oral AD | Week 4 | -9.8 | Standard Deviation 7.32 | Unit on scale |
1 to 10 of 882Source ClinicalTrials.gov
See all 882 results by groupParticipant flow10
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Esketamine Nasal Spray + Oral Antidepressant (AD) | 336 | |
| Overall Study | STARTED | Quetiapine Extended Release (XR) + Oral AD | 340 | |
| Overall Study | Treated (Safety Analysis Set) | Esketamine Nasal Spray + Oral Antidepressant (AD) | 334 | |
| Overall Study | Treated (Safety Analysis Set) | Quetiapine Extended Release (XR) + Oral AD | 336 | |
| Overall Study | Completed Treatment | Esketamine Nasal Spray + Oral Antidepressant (AD) | 258 | |
| Overall Study | Completed Treatment | Quetiapine Extended Release (XR) + Oral AD | 203 | |
| Overall Study | COMPLETED | Esketamine Nasal Spray + Oral Antidepressant (AD) | 274 | |
| Overall Study | COMPLETED | Quetiapine Extended Release (XR) + Oral AD | 232 | |
| Overall Study | NOT COMPLETED | Esketamine Nasal Spray + Oral Antidepressant (AD) | 62 | |
| Overall Study | NOT COMPLETED | Quetiapine Extended Release (XR) + Oral AD | 108 |
Source ClinicalTrials.gov
Adverse events90
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Vertigo | Ear and labyrinth disorders | Esketamine Nasal Spray + Oral Antidepressant (AD) | 63 | 334 | |
| other | Vertigo | Ear and labyrinth disorders | Quetiapine Extended Release (XR) + Oral AD | 3 | 336 | |
| other | Vision blurred | Eye disorders | Esketamine Nasal Spray + Oral Antidepressant (AD) | 21 | 334 | |
| other | Vision blurred | Eye disorders | Quetiapine Extended Release (XR) + Oral AD | 3 | 336 | |
| other | Dry mouth | Gastrointestinal disorders | Esketamine Nasal Spray + Oral Antidepressant (AD) | 3 | 334 | |
| other | Dry mouth | Gastrointestinal disorders | Quetiapine Extended Release (XR) + Oral AD | 22 | 336 | |
| other | Nausea | Gastrointestinal disorders | Esketamine Nasal Spray + Oral Antidepressant (AD) | 98 | 334 | |
| other | Nausea | Gastrointestinal disorders | Quetiapine Extended Release (XR) + Oral AD | 12 | 336 | |
| other | Vomiting | Gastrointestinal disorders | Esketamine Nasal Spray + Oral Antidepressant (AD) | 36 | 334 | |
| other | Vomiting | Gastrointestinal disorders | Quetiapine Extended Release (XR) + Oral AD | 5 | 336 |
1 to 10 of 90Source ClinicalTrials.gov
See all 90 adverse eventsAdverse event totals6
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Esketamine Nasal Spray + Oral Antidepressant (AD) | 1 | 334 |
| Total, all-cause mortality | Quetiapine Extended Release (XR) + Oral AD | 1 | 336 |
| Total, other adverse events | Esketamine Nasal Spray + Oral Antidepressant (AD) | 289 | 334 |
| Total, other adverse events | Quetiapine Extended Release (XR) + Oral AD | 216 | 336 |
| Total, serious adverse events | Esketamine Nasal Spray + Oral Antidepressant (AD) | 19 | 334 |
| Total, serious adverse events | Quetiapine Extended Release (XR) + Oral AD | 17 | 336 |
Source ClinicalTrials.gov
Papers5
The papers the trial lists on ClinicalTrials.gov.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons4
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
| Comparison | Source |
|---|---|
| Esketamine Nasal Spray + Oral Antidepressant (AD) vs Quetiapine Extended Release (XR) + Oral AD: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Trial comparisons |
| Esketamine Nasal Spray + Oral Antidepressant (AD) vs Quetiapine Extended Release (XR) + Oral AD: Number of Participants With TEAEs of Special Interest | Trial comparisons |
| Esketamine Nasal Spray + Oral Antidepressant (AD) vs Quetiapine Extended Release (XR) + Oral AD: deaths from any cause | Trial comparisons |
| Esketamine Nasal Spray + Oral Antidepressant (AD) vs Quetiapine Extended Release (XR) + Oral AD: serious adverse events | Trial comparisons |
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
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