Trial · NCT02493868
A Study of Intranasal Esketamine Plus an Oral Antidepressant for Relapse Prevention in Adult Participants With Treatment-resistant Depression
NCT02493868, Phase 3, Completed, Janssen Research & Development, LLC; results first posted 2019-05-21
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ConductScience Library. A Study of Intranasal Esketamine Plus an Oral Antidepressant for Relapse Prevention in Adult Participants With Treatment-resistant Depression. Trials, record NCT02493868. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT02493868
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- A Study of Intranasal Esketamine Plus an Oral Antidepressant for Relapse Prevention in Adult Participants With Treatment-resistant Depression
- NCT number
- NCT02493868
- Status
- Completed
- Phases
- Phase 3
- Enrollment
- 719 participants, actual
- Lead sponsor
- Janssen Research & Development, LLC
- Conditions
- Depressive Disorder, Treatment-Resistant
- Interventions
- Esketamine, Placebo, Duloxetine (Oral Antidepressant), Escitalopram (Oral antidepressant), Sertraline (Oral Antidepressant), Venlafaxine Extended Release (XR) (Oral Antidepressant)
- First posted
- 2015-07-10
- Last updated
- 2025-04-29
- Other registries' IDs
- eudract:2014-004586-24
- Results first posted
- 2019-05-21
Source ClinicalTrials.gov
Registered outcomes18
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Time to Relapse in Participants With Stable Remission (Maintenance Phase) | Time from randomization to the first relapse during the maintenance phase (up to 92 Weeks) | Relapse is defined as any of following: Montgomery-asberg depression rating scale (MADRS) total score greater than or equal to (\>=) 22 for 2 consecutive assessments separated by 5-15 days and/or hospitalization for worsening depression or any other clinically relevant event to be suggestive of a relapse of depressive illness such as suicide attempt/completed suicide/hospitalization for suicide prevention; If hospitalized, start date of hospitalization will be date of relapse, if not hospitalized date of event will be used. MADRS: clinician-rated scale to measure depression severity and to detect changes due to antidepressant treatment. It has 10 items, scored from 0-6 (not present/normal-severe/continuous symptoms), with total score of 60. Higher scores mean more severe condition. Stable remission: MADRS total score less than or equal to (\<=) 12 for at least 3 of last 4 weeks of OP phase, with 1 excursion total score greater than (\>) 12 or one missing assessment at OP week 13 or 14. |
| Secondary | Time to Relapse in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase) | Time from randomization to the first relapse during the maintenance phase (up to 92 Weeks) | Relapse is defined as any of following: MADRS total score \>= 22 for 2 consecutive assessments separated by 5-15 days and/or hospitalization for worsening depression or any other clinically relevant event to be suggestive of a relapse of depressive illness such as suicide attempt/completed suicide/hospitalization for suicide prevention; If hospitalized, start date of hospitalization will be date of relapse, if not hospitalized date of event will be used. MADRS: clinician-rated scale to measure depression severity and to detect changes due to antidepressant treatment. It has 10 items, scored from 0-6 (not present/normal-severe/continuous symptoms), with total score of 60. Higher scores mean more severe condition. Stable response is defined as \>= 50 percent (%) reduction in MADRS total score from baseline (Day 1 of induction phase, prior to first intranasal dose) in each of the last 2 weeks of the OP phase, but without meeting criteria for stable remission. |
| Secondary | Change From Baseline in MADRS Total Score at Endpoint in Participants With Stable Remission (Maintenance Phase) | Baseline and Endpoint (Up to 92 Weeks) | MADRS: clinician-rated scale to measure depression severity and to detect changes due to antidepressant treatment. It has 10 items, scored from 0-6 (not present/normal - severe/continuous symptoms), with total score of 60. Higher scores mean more severe condition. The change from baseline in MADRS total score (last observation carried forward \[LOCF\] data), at endpoint was reported. The last post baseline observation was carried forward as the endpoint. |
| Secondary | Change From Baseline in MADRS Total Score at Endpoint in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase) | Baseline and Endpoint (Up to 92 Weeks) | MADRS: clinician-rated scale to measure depression severity and to detect changes due to antidepressant treatment. It has 10 items, scored from 0-6 (not present/normal - severe/continuous symptoms), with total score of 60. Higher scores mean more severe condition. The change from baseline in MADRS total score (LOCF data), at endpoint was reported. The last post baseline observation was carried forward as the endpoint. |
| Secondary | Change From Baseline in Patient Health Questionnaire-9 (PHQ-9) Total Score at Endpoint in Participants With Stable Remission (Maintenance Phase) | Baseline and Endpoint (Up to 92 Weeks) | PHQ-9 is a 9-item, self-report scale assessing 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). The change from baseline in PHQ-9 total score, (LOCF data) at endpoint was reported. The last post baseline observation was carried forward as the endpoint. |
| Secondary | Change From Baseline in PHQ-9 Total Score at Endpoint in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase) | Baseline and Endpoint (Up to 92 Weeks) | PHQ-9 is a 9-item, self-report scale assessing 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). The change from baseline in PHQ-9 total score, (LOCF data) at endpoint was reported. The last post baseline observation was carried forward as the endpoint. |
| Secondary | Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Endpoint in Participants With Stable Remission (Maintenance Phase) | Baseline and Endpoint (Up to 92 Weeks) | 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 0 to 7. Considering total clinical experience, a participant is assessed on severity of mental illness at the time of rating according to: 0=not assessed; 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 change from baseline in CGI-S score, (LOCF data) at endpoint was reported. The last post baseline observation was carried forward as the endpoint. |
| Secondary | Change From Baseline in Clinical Global Impression-Severity Score at Endpoint in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase) | Baseline and Endpoint (Up to 92 Weeks) | 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 0 to 7. Considering total clinical experience, a participant is assessed on severity of mental illness at the time of rating according to: 0=not assessed; 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 change from baseline in CGI-S score, (LOCF data) at endpoint was reported. The last post baseline observation was carried forward as the endpoint. |
| Secondary | Change From Baseline in Generalized Anxiety Disorder-7 Items (GAD-7) Total Score at Endpoint in Participants With Stable Remission (Maintenance Phase) | Baseline and Endpoint (Up to 92 Weeks) | GAD-7 is a brief and validated 7-item self-report 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). Item responses are summed to yield a total score (range of 0 to 21), with higher scores indicating more anxiety. The change from baseline in GAD-7 total score, (LOCF data), at endpoint was reported. The last post baseline observation was carried forward as the endpoint. |
| Secondary | Change From Baseline in Generalized Anxiety Disorder-7 Items Total Score at Endpoint in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase) | Baseline and Endpoint (Up to 92 Weeks) | GAD-7 is a brief and validated 7-item self-report 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). Item responses are summed to yield a total score (range of 0 to 21), with higher scores indicating more anxiety. The change from baseline in GAD-7 total score, (LOCF data), at endpoint was reported. The last post baseline observation was carried forward as the endpoint. |
1 to 10 of 18Source ClinicalTrials.gov
See all 18 registered outcomesOutcomes18
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Time to Relapse in Participants With Stable Remission (Maintenance Phase) | Time from randomization to the first relapse during the maintenance phase (up to 92 Weeks) | Full (stable remitters) analysis set included all the randomized participants who were in stable remission at the end of the optimization phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during the maintenance phase. | Days | MEDIAN |
| SECONDARY | Time to Relapse in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase) | Time from randomization to the first relapse during the maintenance phase (up to 92 Weeks) | Full (stable responders) analysis set included all randomized participants who were stable responders (who were not stable remitters) at the end of the optimization phase and who received at least 1 dose of intranasal study drug and 1 dose of oral antidepressant during the maintenance phase. | Days | MEDIAN |
| SECONDARY | Change From Baseline in MADRS Total Score at Endpoint in Participants With Stable Remission (Maintenance Phase) | Baseline and Endpoint (Up to 92 Weeks) | Full (stable remitters) analysis set included all randomized participants who were in stable remission at end of OP phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this outcome measure (OM). | Units on a scale | MEAN |
| SECONDARY | Change From Baseline in MADRS Total Score at Endpoint in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase) | Baseline and Endpoint (Up to 92 Weeks) | Full (stable responders) analysis set included all randomized participants who were stable responders (who were not stable remitters) at the end of the optimization phase and who received at least 1 dose of intranasal study drug and 1 dose of oral antidepressant during the maintenance phase. | Units on a scale | MEAN |
| SECONDARY | Change From Baseline in Patient Health Questionnaire-9 (PHQ-9) Total Score at Endpoint in Participants With Stable Remission (Maintenance Phase) | Baseline and Endpoint (Up to 92 Weeks) | Full (stable remitters) analysis set included all randomized participants who were in stable remission at the end of OP phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this OM. | Units on a scale | MEAN |
| SECONDARY | Change From Baseline in PHQ-9 Total Score at Endpoint in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase) | Baseline and Endpoint (Up to 92 Weeks) | Full (stable responders) analysis set: all randomized participants who were stable responders (not stable remitters) at end of OP phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this OM. | Units on a scale | MEAN |
| SECONDARY | Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Endpoint in Participants With Stable Remission (Maintenance Phase) | Baseline and Endpoint (Up to 92 Weeks) | Full (stable remitters) analysis set included all randomized participants who were in stable remission at the end of OP phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this OM. | Units on a scale | MEDIAN |
| SECONDARY | Change From Baseline in Clinical Global Impression-Severity Score at Endpoint in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase) | Baseline and Endpoint (Up to 92 Weeks) | Full (stable responders) analysis set: all randomized participants who were stable responders (not stable remitters) at end of OP phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this OM. | Units on a scale | MEDIAN |
| SECONDARY | Change From Baseline in Generalized Anxiety Disorder-7 Items (GAD-7) Total Score at Endpoint in Participants With Stable Remission (Maintenance Phase) | Baseline and Endpoint (Up to 92 Weeks) | Full (stable remitters) analysis set included all randomized participants who were in stable remission at the end of OP phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this OM. | Units on a scale | MEAN |
| SECONDARY | Change From Baseline in Generalized Anxiety Disorder-7 Items Total Score at Endpoint in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase) | Baseline and Endpoint (Up to 92 Weeks) | Full (stable responders) analysis set: all randomized participants who were stable responders (not stable remitters) at end of OP phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this OM. | Units on a scale | MEAN |
1 to 10 of 18Source ClinicalTrials.gov
See all 18 outcomesResults by group36
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Time to Relapse in Participants With Stable Remission (Maintenance Phase) | Intranasal Esketamine + Oral AD | NA | 95% Confidence Interval NA to NA | Days | |
| Time to Relapse in Participants With Stable Remission (Maintenance Phase) | Oral AD+ Intranasal Placebo | 273.0 | 95% Confidence Interval 97.0 to NA | Days | |
| Time to Relapse in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase) | Intranasal Esketamine + Oral AD | 635.0 | 95% Confidence Interval 264.0 to 635.0 | Days | |
| Time to Relapse in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase) | Oral AD+ Intranasal Placebo | 88.0 | 95% Confidence Interval 46.0 to 196.0 | Days | |
| Change From Baseline in MADRS Total Score at Endpoint in Participants With Stable Remission (Maintenance Phase) | Intranasal Esketamine + Oral AD | 7.5 | Standard Deviation 11.59 | Units on a scale | |
| Change From Baseline in MADRS Total Score at Endpoint in Participants With Stable Remission (Maintenance Phase) | Oral AD+ Intranasal Placebo | 12.5 | Standard Deviation 13.63 | Units on a scale | |
| Change From Baseline in MADRS Total Score at Endpoint in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase) | Intranasal Esketamine + Oral AD | 4.4 | Standard Deviation 11.38 | Units on a scale | |
| Change From Baseline in MADRS Total Score at Endpoint in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase) | Oral AD+ Intranasal Placebo | 11.4 | Standard Deviation 12.00 | Units on a scale | |
| Change From Baseline in Patient Health Questionnaire-9 (PHQ-9) Total Score at Endpoint in Participants With Stable Remission (Maintenance Phase) | Intranasal Esketamine + Oral AD | 3.3 | Standard Deviation 5.58 | Units on a scale | |
| Change From Baseline in Patient Health Questionnaire-9 (PHQ-9) Total Score at Endpoint in Participants With Stable Remission (Maintenance Phase) | Oral AD+ Intranasal Placebo | 5.9 | Standard Deviation 7.09 | Units on a scale |
1 to 10 of 36Source ClinicalTrials.gov
See all 36 results by groupParticipant flow28
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Induction Phase: DE Participants | STARTED | Intranasal Esketamine + Oral AD | 437 | |
| Induction Phase: DE Participants | STARTED | Oral AD + Intranasal Placebo | 0 | |
| Induction Phase: DE Participants | COMPLETED | Intranasal Esketamine + Oral AD | 273 | |
| Induction Phase: DE Participants | COMPLETED | Oral AD + Intranasal Placebo | 0 | |
| Induction Phase: DE Participants | NOT COMPLETED | Intranasal Esketamine + Oral AD | 164 | |
| Induction Phase: DE Participants | NOT COMPLETED | Oral AD + Intranasal Placebo | 0 | |
| Optimization Phase: DE+TE Participants | STARTED | Intranasal Esketamine + Oral AD | 455 | |
| Optimization Phase: DE+TE Participants | STARTED | Oral AD + Intranasal Placebo | 86 | |
| Optimization Phase: DE+TE Participants | COMPLETED | Intranasal Esketamine + Oral AD | 297 | |
| Optimization Phase: DE+TE Participants | COMPLETED | Oral AD + Intranasal Placebo | 54 |
1 to 10 of 28Source ClinicalTrials.gov
See all 28 participant flowAdverse events440
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 | IND: Intranasal Esketamine + Oral AD | 99 | 437 | |
| other | Vertigo | Ear and labyrinth disorders | OP: Intranasal Esketamine + Oral AD | 91 | 455 | |
| other | Vertigo | Ear and labyrinth disorders | MA: Intranasal Esketamine + Oral AD | 38 | 152 | |
| other | Vertigo | Ear and labyrinth disorders | MA: Oral AD + Intranasal Placebo | 8 | 145 | |
| other | Vertigo | Ear and labyrinth disorders | FU: Intranasal Esketamine + Oral AD | 2 | 481 | |
| other | Vertigo | Ear and labyrinth disorders | FU: Oral AD + Intranasal Placebo | 0 | 64 | |
| other | Vertigo | Ear and labyrinth disorders | OP_TEP: Oral AD + Intranasal Placebo | 0 | 86 | |
| other | Vertigo | Ear and labyrinth disorders | MA_TEP: Oral AD + Intranasal Placebo | 0 | 54 | |
| other | Diplopia | Eye disorders | IND: Intranasal Esketamine + Oral AD | 16 | 437 | |
| other | Diplopia | Eye disorders | OP: Intranasal Esketamine + Oral AD | 10 | 455 |
1 to 10 of 440Source ClinicalTrials.gov
See all 440 adverse eventsAdverse event totals24
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | IND: Intranasal Esketamine + Oral AD | 0 | 437 |
| Total, all-cause mortality | OP: Intranasal Esketamine + Oral AD | 0 | 455 |
| Total, all-cause mortality | MA: Intranasal Esketamine + Oral AD | 0 | 152 |
| Total, all-cause mortality | MA: Oral AD + Intranasal Placebo | 0 | 145 |
| Total, all-cause mortality | FU: Intranasal Esketamine + Oral AD | 0 | 481 |
| Total, all-cause mortality | FU: Oral AD + Intranasal Placebo | 0 | 64 |
| Total, all-cause mortality | OP_TEP: Oral AD + Intranasal Placebo | 0 | 86 |
| Total, all-cause mortality | MA_TEP: Oral AD + Intranasal Placebo | 0 | 54 |
| Total, other adverse events | IND: Intranasal Esketamine + Oral AD | 306 | 437 |
| Total, other adverse events | OP: Intranasal Esketamine + Oral AD | 279 | 455 |
1 to 10 of 24Source ClinicalTrials.gov
See all 24 adverse event totalsPapers8
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 comparisons0
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
None in this release.
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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