Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT07227454 | A Study to Evaluate the Efficacy and Safety of Esketamine for Reduction of Symptoms of Major Depressive Disorder | PHASE3 | RECRUITING | 258 | — | — | Jan 8, 2026 | Sep 15, 2031 | Jun 5, 2026 | 27 | United States, Brazil +4 |
| 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 | PHASE3 | COMPLETED | 676 | — | — | Aug 21, 2020 | Jul 15, 2022 | Apr 29, 2025 | 171 | Argentina, Austria +22 |
| NCT03097133 | 54135419SUI3002: A Study to Evaluate the Efficacy and Safety of Intranasal Esketamine in Addition to Comprehensive Standard of Care for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicidal Ideation, in Adult Participants Assessed to be at Imminent Risk for Suicide | PHASE3 | COMPLETED | 230 | — | — | Jun 15, 2017 | Apr 11, 2019 | Apr 29, 2025 | 61 | United States, Argentina +10 |
| NCT03039192 | 54135419SUI3001: A Study to Evaluate the Efficacy and Safety of Intranasal Esketamine in Addition to Comprehensive Standard of Care for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicidal Ideation, in Adult Participants Assessed to be at Imminent Risk for Suicide | PHASE3 | COMPLETED | 226 | — | — | Jun 9, 2017 | Dec 18, 2018 | Apr 29, 2025 | 56 | United States, Bulgaria +9 |
| NCT03185819 | Study to Evaluate the Efficacy and Safety of 3 Fixed Doses of Intranasal Esketamine in Addition to Comprehensive Standard of Care for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicidal Ideation, in Pediatric Participants Assessed to be at Imminent Risk for Suicide | PHASE2 | COMPLETED | 147 | — | — | Oct 5, 2017 | Mar 31, 2023 | Apr 29, 2025 | 51 | United States, Belgium +7 |
| NCT02919579 | A Study to Evaluate the Effects of a Single-Dose and Repeat-Administration of Intranasal Esketamine on On-Road Driving in Participants With Major Depressive Disorder | PHASE1 | COMPLETED | 27 | — | — | Oct 7, 2016 | Jun 29, 2018 | Apr 27, 2025 | 1 | Netherlands |
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.
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.
MADRS is clinician-rated scale designed to be used in participants with Major Depressive Disorder (MDD) to measure depression severity and detect changes due to antidepressant treatment. It evaluates apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic and suicidal thoughts. Scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms), summed for total possible score of 0 to 60. Higher scores represent more severe condition. Negative change in score indicates improvement.
Clinical global impression-severity of suicidality-revised (CGI-SS-R) scale is revised version of the clinical global impression severity scale (CGI-S),a global rating scale that gives an overall measure of the severity of a participants illness. The CGI-SS-R summarizes the clinician's overall impression of severity of suicidality on a 7-point scale from 0 (normal, not at all suicidal) to 6 (among the most extremely suicidal participants), based on the totality of information available to the clinician. Higher score indicates a more severe condition. Negative change in score indicates improvement.
MADRS is clinician-rated scale designed to be used in participants with Major Depressive Disorder (MDD) to measure depression severity and detect changes due to antidepressant treatment. It evaluates apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic and suicidal thoughts. Scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms), summed for total possible score of 0 to 60. Higher scores represent more severe condition. Negative change in score indicates improvement.
The CDRS-R is a validated 17- item, clinician-rated instrument developed to assess depressive symptomatology in children. Scores were based on interviews with both the child and their caregiver. 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.
Driving performance will be assessed by the mean difference of standard deviation of lateral position (SDLP) from an on-road driving test.
Driving performance will be assessed by the mean difference of standard deviation of lateral position (SDLP) from an on-road driving test.
| Arm | Type | Description |
|---|---|---|
| Intranasal Esketamine + Oral Placebo | EXPERIMENTAL | 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. |
| Intranasal Placebo + Oral Midazolam | PLACEBO_COMPARATOR | 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. |
| Esketamine Arm | EXPERIMENTAL | Participants will receive treatment with esketamine nasal spray (28 milligram \[mg\] \[initial dose for elderly participants 65 to 74 years of age and adults of Japanese ancestry; may be used throughout the study in these populations; may be uptitrated in 28 mg increments\], 56 mg \[initial dose for adult participants aged 18 to 64 years and may be used for all age groups throughout the study\], or 84 mg \[maximum dose esketamine nasal spray may be uptitrated to\]) twice-weekly with a flexible dose regimen from Day 1 until Week 4, once weekly from Week 5 to Week 8 and once-weekly or once every 2 weeks from Week 9 to Week 32 in combination with continuing serotonin-norepinephrine reuptake inhibitor/selective serotonin reuptake inhibitor (SSRI/SNRI). |
| Comparator Arm | ACTIVE_COMPARATOR | Participants will continue to take their current SSRI/SNRI augmented with quetiapine extended release (XR) as per the Summary of Product Characteristics (SmPC) (or local equivalent, if applicable). In adult participants aged 18 to 64 years, the initial dose is 50 mg/day on Days 1-2, 150 mg/day on Days 3-4 \[lowest effective dose\]; a further dose increase to 300 mg/day on Day 5 and onward will be based on individual participant evaluation. In elderly participants aged 65 to 74 years, the initial dose is 50 mg/day on Days 1-3, 100 mg/day on Days 4-7, and 150 mg/day on Day 8; a further dose increase to 300 mg/day will be based on individual participant evaluation no earlier than Day 22. |
| Esketamine + Standard of care | EXPERIMENTAL | Participants will receive intranasal esketamine 84 milligram (mg) on Day 1, 4, 8, 11, 15, 18, 22, and 25 along with standard of care antidepressant treatment. |
| Placebo + Standard of care | PLACEBO_COMPARATOR | Participants will receive intranasal placebo on Day 1, 4, 8, 11, 15, 18, 22, and 25 along with standard of care antidepressant treatment. |
| Oral Midazolam + Intranasal Placebo | PLACEBO_COMPARATOR | Participants will receive midazolam solution 0.125 milligram per kilogram (mg/kg) orally 2 times per week for 4 weeks and 3 intranasal doses of matched placebo to esketamine. |
| Oral Placebo + Esketamine 84 mg | EXPERIMENTAL | Participants will receive intranasal esketamine 84 mg as 3 intranasal doses of esketamine in each nostril (each dose contains 14 mg of esketamine) along with oral placebo 2 times per week for 4 weeks. |
| Oral Placebo + Esketamine 56 mg | EXPERIMENTAL | Participants will receive intranasal esketamine 56 mg as 2 intranasal doses of esketamine in each nostril (each dose contains 14 mg of esketamine) along with oral placebo 2 times per week for 4 weeks. |
| Oral Placebo + Esketamine 28 mg | EXPERIMENTAL | Participants will receive intranasal esketamine 28 mg as 1 intranasal doses of esketamine in each nostril (each dose contains 14 mg of esketamine) along with oral placebo 2 times per week for 4 weeks. |
| Part A: Sequence ABC (Placebo+Alcohol+Esketamine) | EXPERIMENTAL | Participants will receive intranasal placebo on Day 1 and oral placebo on Day 2 \[Treatment A\] in Period 1, then intranasal placebo on Day 1 and Oral alcohol on Day 2 \[Treatment B\] in Period 2, followed by intranasal esketamine on Day 1 and oral placebo on Day 2 \[Treatment C\] in Period 3. |
| Part A: Sequence BCA (Placebo+Alcohol+Esketamine) | EXPERIMENTAL | Participants will receive Treatment B in Period 1, then Treatment C in Period 2, followed by Treatment A in Period 3. |
| Part A: Sequence CAB (Placebo+Alcohol+Esketamine) | EXPERIMENTAL | Participants will receive Treatment C in Period 1, then Treatment A in Period 2, followed by Treatment B in Period 3. |
| Part A: Sequence CBA (Placebo+Alcohol+Esketamine) | EXPERIMENTAL | Participants will receive Treatment C in Period 1, then Treatment B in Period 2, followed by Treatment A in Period 3. |
| Part A: Sequence ACB (Placebo+Alcohol+Esketamine) | EXPERIMENTAL | Participants will receive Treatment A in Period 1, then Treatment C in Period 2, followed by Treatment B in Period 3. |
| Part A: Sequence BAC (Placebo+Alcohol+Esketamine) | EXPERIMENTAL | Participants will receive Treatment B in Period 1, then Treatment A in Period 2, followed by Treatment C in Period 3. |
| Part B: Placebo+Esketamine | EXPERIMENTAL | Participants will receive intranasal placebo on Day 1, followed by intranasal esketamine on Days 4, 8, 11, 15, 18, 22 and 25. |
| Name | Type | Description |
|---|---|---|
| Esketamine | DRUG | Esketamine will be administered as intranasal solution. |
| Midazolam | DRUG | Midazolam will be administered as oral solution. |
| Oral Placebo | OTHER | Placebo will be administered as oral solution. |
| Intranasal Placebo | OTHER | Intranasal placebo will be administered as nasal solution. |
| Esketamine 28 mg | DRUG | Esketamine will be self-administered at a dose of 28 mg as nasal spray. |
| Esketamine 56 mg | DRUG | Esketamine will be self-administered at a dose of 56 mg as nasal spray. |
| Esketamine 84 mg | DRUG | Esketamine will be self-administered at a dose of 84 mg (maximum uptitrated dose) as nasal spray. |
| Quetiapine XR 50 mg | DRUG | Quetiapine XR will be administered at an initial dose of 50 mg/day and may be further increased to 300 mg/day based on individual participant evaluation. |
| Quetiapine XR 100 mg | DRUG | Quetiapine XR will be administered at a dose of 100 mg/day and may be further increased to 300 mg/day based on individual participant evaluation. |
| Quetiapine XR 150 mg | DRUG | Quetiapine XR will be administered at a dose of 150 mg/day and may be further increased to 300 mg/day based on individual participant evaluation. |
| SSRI/SNRI | DRUG | Participants will continue to take SSRI/SNRI that is approved for use in depression in their country of participation; off-label use of any SSRI/SNRI is not permitted. The continuing SSRI/SNRI dosage may be optimized throughout the study, at the investigator's discretion and based on the SmPC (or local equivalent, if applicable). |
| Placebo | DRUG | Participants will receive intranasal placebo two times per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25). |
| Standard of Care | OTHER | The standard of care antidepressant treatment (antidepressant monotherapy or antidepressant plus augmentation therapy) will be determined by the treating physician(s) based on clinical judgement and practice guidelines prior to randomization, and the treatment will be initiated on Day 1. |
| Midazolam Placebo Solution | DRUG | Participants will receive placebo as oral dose to match midazolam drug. |
| Placebo (Intranasal) | DRUG | Participants will receive intranasal placebo in Part A (as per the treatment sequence in period 1,2 and 3) and Part B. |
| Alcohol | OTHER | Participants will receive oral alcohol in Part A (as per the treatment sequence in period 1,2 and 3). |
| Placebo (Oral) | DRUG | Participants will receive oral placebo in Part A (as per the treatment sequence in period 1,2 and 3). |
Inclusion Criteria: * Must meet diagnostic and statistical manual of mental disorders (5th edition) (DSM-5) diagnostic criteria for major depressive disorder (MDD) based upon clinical assessment and confirmed by the mini-international neuropsychiatric interview for children and adolescents (MINI-KI...