Trial · NCT03434041
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
NCT03434041, Phase 3, Completed, Janssen Research & Development, LLC; results first posted 2022-05-24
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. 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. Trials, record NCT03434041. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT03434041
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- 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
- NCT number
- NCT03434041
- Status
- Completed
- Phases
- Phase 3
- Enrollment
- 252 participants, actual
- Lead sponsor
- Janssen Research & Development, LLC
- Conditions
- Depressive Disorder, Treatment-Resistant
- Interventions
Esketamine 56 mg, Esketamine 84 mg, Placebo, Duloxetine (Oral Antidepressant), Escitalopram (Oral Antidepressant), Sertraline (Oral Antidepressant), Venlafaxine Extended Release (XR) (Oral Antidepressant)
- First posted
- 2018-02-15
- Last updated
- 2025-04-29
- Results first posted
- 2022-05-24
- Limitations and caveats
As esketamine has known transient dissociative effects that are difficult to blind, these specific treatment-emergent events could have biased the staff who provided and observed the dosing. Therefore, to ensure an unbiased efficacy evaluation, independent, remote (by telephone), blinded MADRS raters were used to assess the treatment response.
Source ClinicalTrials.gov
Registered outcomes12
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score to the End of Double-blind Treatment Phase (Day 28) | Baseline up to end of the 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 | Change From Baseline in Depressive Symptoms as Measured by the MADRS Total Score to 24 Hours Post First Dose (Day 2) | Baseline (Day 1: predose) to 24 hours post first dose (Day 2) | 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 | Change From Baseline in Sheehan Disability Scale (SDS) Total Score to the End of Double-blind Treatment Phase (Day 28) | Baseline up to end of the 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. |
| Secondary | Percentage of Participants With Onset of Clinical Response | Day 2 up to Day 28 | 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. |
| Secondary | Percentage of Responders at the End of Double-blind Treatment Phase (Day 28) | 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. |
| Secondary | Percentage of Participants in Remission at the End of Double-blind Treatment Phase (Day 28) | 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. |
| Secondary | Percentage of Participants With Sustained Remission | Up to Day 28 | 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. |
| Secondary | Change From Baseline in Clinical Global Impression Severity (CGI-S) Scale Score up to the Endpoint (Double-blind Treatment Phase [Day 28]) | Baseline up to Double-blind Endpoint (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. |
| Secondary | Change From Baseline in Generalized Anxiety Disorder 7-item (GAD-7) Scale Score up to the Endpoint (Double-blind Treatment Phase [Day 28]) | Baseline up to 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". |
| Secondary | 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 | Baseline up to Double-blind Endpoint (Day 28) | 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. |
1 to 10 of 12Source ClinicalTrials.gov
See all 12 registered outcomesOutcomes12
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score to the End of Double-blind Treatment Phase (Day 28) | Baseline up to end of the double-blind treatment phase (Day 28) | Full analysis set included all randomized participants who received a least 1 dose of intranasal study medication and 1 dose of oral antidepressant medication during the double-blind treatment phase. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. | Units on a Scale | MEAN |
| SECONDARY | Change From Baseline in Depressive Symptoms as Measured by the MADRS Total Score to 24 Hours Post First Dose (Day 2) | Baseline (Day 1: predose) to 24 hours post first dose (Day 2) | Full analysis set included all randomized participants who received a least 1 dose of intranasal study medication and 1 dose of oral antidepressant medication during the double-blind treatment phase. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. | Units on a Scale | MEAN |
| SECONDARY | Change From Baseline in Sheehan Disability Scale (SDS) Total Score to the End of Double-blind Treatment Phase (Day 28) | Baseline up to end of the double-blind treatment phase (Day 28) | Full analysis set included all randomized participants who received a least 1 dose of intranasal study medication and 1 dose of oral antidepressant medication during the double-blind treatment phase. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. | Units on a Scale | MEAN |
| SECONDARY | Percentage of Participants With Onset of Clinical Response | Day 2 up to Day 28 | Full analysis set included all randomized participants who received a least 1 dose of intranasal study medication and 1 dose of oral antidepressant medication during the double-blind treatment phase. | Percentage of participants | NUMBER |
| SECONDARY | Percentage of Responders at the End of Double-blind Treatment Phase (Day 28) | Day 28 | Full analysis set included all randomized participants who received a least 1 dose of intranasal study medication and 1 dose of oral antidepressant medication during the double-blind treatment phase. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. | Percentage of Responders | NUMBER |
| SECONDARY | Percentage of Participants in Remission at the End of Double-blind Treatment Phase (Day 28) | Day 28 | Full analysis set included all randomized participants who received a least 1 dose of intranasal study medication and 1 dose of oral antidepressant medication during the double-blind treatment phase. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. | Percentage of Participants | NUMBER |
| SECONDARY | Percentage of Participants With Sustained Remission | Up to Day 28 | Full analysis set included all randomized participants who received a least 1 dose of intranasal study medication and 1 dose of oral antidepressant medication during the double-blind treatment phase. | Percentage of Participants | NUMBER |
| SECONDARY | Change From Baseline in Clinical Global Impression Severity (CGI-S) Scale Score up to the Endpoint (Double-blind Treatment Phase [Day 28]) | Baseline up to Double-blind Endpoint (Day 28) | Full analysis set included all randomized participants who received a least 1 dose of intranasal study medication and 1 dose of oral antidepressant medication during the double-blind treatment phase. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. | Units on a Scale | MEDIAN |
| SECONDARY | Change From Baseline in Generalized Anxiety Disorder 7-item (GAD-7) Scale Score up to the Endpoint (Double-blind Treatment Phase [Day 28]) | Baseline up to Endpoint (double-blind treatment phase [Day 28]) | Full analysis set included all randomized participants who received a least 1 dose of intranasal study medication and 1 dose of oral antidepressant medication during the double-blind treatment phase. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. | Units on a Scale | MEAN |
| SECONDARY | 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 | Baseline up to Double-blind Endpoint (Day 28) | Full analysis set included all randomized participants who received a least 1 dose of intranasal study medication and 1 dose of oral antidepressant medication during the double-blind treatment phase. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. | Units on a Scale | MEAN |
1 to 10 of 12Source ClinicalTrials.gov
See all 12 outcomesResults by group24
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score to the End of Double-blind Treatment Phase (Day 28) | Intranasal Esketamine + Oral Antidepressant (AD) | -10.1 | Standard Deviation 10.80 | Units on a Scale | |
| Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score to the End of Double-blind Treatment Phase (Day 28) | Intranasal Placebo + Oral AD | -8.1 | Standard Deviation 10.26 | Units on a Scale | |
| Change From Baseline in Depressive Symptoms as Measured by the MADRS Total Score to 24 Hours Post First Dose (Day 2) | Intranasal Esketamine + Oral Antidepressant (AD) | -8.0 | Standard Deviation 9.01 | Units on a Scale | |
| Change From Baseline in Depressive Symptoms as Measured by the MADRS Total Score to 24 Hours Post First Dose (Day 2) | Intranasal Placebo + Oral AD | -4.4 | Standard Deviation 7.66 | Units on a Scale | |
| Change From Baseline in Sheehan Disability Scale (SDS) Total Score to the End of Double-blind Treatment Phase (Day 28) | Intranasal Esketamine + Oral Antidepressant (AD) | -6.3 | Standard Deviation 7.54 | Units on a Scale | |
| Change From Baseline in Sheehan Disability Scale (SDS) Total Score to the End of Double-blind Treatment Phase (Day 28) | Intranasal Placebo + Oral AD | -5.3 | Standard Deviation 7.03 | Units on a Scale | |
| Percentage of Participants With Onset of Clinical Response | Intranasal Esketamine + Oral Antidepressant (AD) | 6.5 | Percentage of participants | ||
| Percentage of Participants With Onset of Clinical Response | Intranasal Placebo + Oral AD | 1.6 | Percentage of participants | ||
| Percentage of Responders at the End of Double-blind Treatment Phase (Day 28) | Intranasal Esketamine + Oral Antidepressant (AD) | 19.3 | Percentage of Responders | ||
| Percentage of Responders at the End of Double-blind Treatment Phase (Day 28) | Intranasal Placebo + Oral AD | 16.0 | Percentage of Responders |
1 to 10 of 24Source ClinicalTrials.gov
See all 24 results by groupParticipant flow14
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Double Blind Treatment Phase (4 Weeks) | STARTED | Intranasal Esketamine + Oral Antidepressant (AD) | 126 | |
| Double Blind Treatment Phase (4 Weeks) | STARTED | Intranasal Placebo + Oral AD | 126 | |
| Double Blind Treatment Phase (4 Weeks) | Full Analysis Set | Intranasal Esketamine + Oral Antidepressant (AD) | 124 | |
| Double Blind Treatment Phase (4 Weeks) | Full Analysis Set | Intranasal Placebo + Oral AD | 126 | |
| Double Blind Treatment Phase (4 Weeks) | COMPLETED | Intranasal Esketamine + Oral Antidepressant (AD) | 108 | |
| Double Blind Treatment Phase (4 Weeks) | COMPLETED | Intranasal Placebo + Oral AD | 106 | |
| Double Blind Treatment Phase (4 Weeks) | NOT COMPLETED | Intranasal Esketamine + Oral Antidepressant (AD) | 18 | |
| Double Blind Treatment Phase (4 Weeks) | NOT COMPLETED | Intranasal Placebo + Oral AD | 20 | |
| Follow-up Phase (Up to 8 Weeks) | STARTED | Intranasal Esketamine + Oral Antidepressant (AD) | 106 | |
| Follow-up Phase (Up to 8 Weeks) | STARTED | Intranasal Placebo + Oral AD | 103 |
1 to 10 of 14Source ClinicalTrials.gov
See all 14 participant flowAdverse events96
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 | Vision Blurred | Eye disorders | Double-blind: Intranasal Esketamine+ Oral Antidepressant (AD) | 23 | 126 | |
| other | Vision Blurred | Eye disorders | Double-blind: Oral AD + Intranasal Placebo | 1 | 126 | |
| other | Vision Blurred | Eye disorders | Follow-up: Intranasal Esketamine+ Oral AD | 0 | 106 | |
| other | Vision Blurred | Eye disorders | Follow-up: Oral AD + Intranasal Placebo | 0 | 103 | |
| other | Constipation | Gastrointestinal disorders | Double-blind: Intranasal Esketamine+ Oral Antidepressant (AD) | 3 | 126 | |
| other | Constipation | Gastrointestinal disorders | Double-blind: Oral AD + Intranasal Placebo | 2 | 126 | |
| other | Constipation | Gastrointestinal disorders | Follow-up: Intranasal Esketamine+ Oral AD | 1 | 106 | |
| other | Constipation | Gastrointestinal disorders | Follow-up: Oral AD + Intranasal Placebo | 6 | 103 | |
| other | Hypoaesthesia Oral | Gastrointestinal disorders | Double-blind: Intranasal Esketamine+ Oral Antidepressant (AD) | 10 | 126 | |
| other | Hypoaesthesia Oral | Gastrointestinal disorders | Double-blind: Oral AD + Intranasal Placebo | 1 | 126 |
1 to 10 of 96Source ClinicalTrials.gov
See all 96 adverse eventsAdverse event totals12
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Double-blind: Intranasal Esketamine+ Oral Antidepressant (AD) | 1 | 126 |
| Total, all-cause mortality | Double-blind: Oral AD + Intranasal Placebo | 0 | 126 |
| Total, all-cause mortality | Follow-up: Intranasal Esketamine+ Oral AD | 0 | 106 |
| Total, all-cause mortality | Follow-up: Oral AD + Intranasal Placebo | 0 | 103 |
| Total, other adverse events | Double-blind: Intranasal Esketamine+ Oral Antidepressant (AD) | 118 | 126 |
| Total, other adverse events | Double-blind: Oral AD + Intranasal Placebo | 61 | 126 |
| Total, other adverse events | Follow-up: Intranasal Esketamine+ Oral AD | 10 | 106 |
| Total, other adverse events | Follow-up: Oral AD + Intranasal Placebo | 13 | 103 |
| Total, serious adverse events | Double-blind: Intranasal Esketamine+ Oral Antidepressant (AD) | 3 | 126 |
| Total, serious adverse events | Double-blind: Oral AD + Intranasal Placebo | 3 | 126 |
1 to 10 of 12Source ClinicalTrials.gov
See all 12 adverse event totalsPapers0
The papers the trial lists on ClinicalTrials.gov.
None in this release.
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.
For software
Read this trial from software.
The record and each of its lists are JSON, twenty rows a page. No key.
GET https://conductscience.org/api/trials/v1/NCT03434041
GET https://conductscience.org/api/trials/v1/NCT03434041/results?page=2