Depressive Disorder, Treatment-Resistant
Conditions
Keywords
Depressive Disorder, Treatment-Resistant, Esketamine, JNJ-54135419
Brief summary
The purpose of this study is to assess the safety and tolerability of esketamine nasal spray in participants with treatment-resistant depression (TRD).
Detailed description
This is an open-label (the researchers and participants know the treatment the participant is receiving) long-term extension study. The study will consist of 2 open-label Phases: 4-week Induction phase (if applicable) and Open-Label Optimization/Maintenance phase (variable). Participants will enter the study Induction Phase from ESKETINTRD3001 (NCT02417064), ESKETINTRD3002 (NCT02418585), ESKETINTRD3003 (NCT02493868), ESKETINTRD3005 (NCT02422186) and ESKETINTRD3006 (US sites only). Participants will enter the study Open-Label Optimization/Maintenance phase from ESKETINTRD3001 (NCT02417064), ESKETINTRD3002 (NCT02418585), ESKETINTRD3003 (NCT02493868) (if appropriate at week 16) or ESKETINTRD3006 (US sites only). In the Open-Label Induction Phase, participants will self-administer flexibly-dosed esketamine nasal spray. During first 4 weeks in Optimization/Maintenance Phase responder participants from the induction phase of study 54135419TRD3008, will continue on the same dose of esketamine nasal spray from the induction phase and have a weekly intranasal treatment session frequency. Participants entering the optimization/maintenance phase from study ESKETINTRD3005 will also have a weekly intranasal treatment session frequency. However, as the ESKETINTRD3005 intranasal study medication is blinded at the time of entry into the current study, the dose of esketamine nasal spray will be administered as outlined in protocol. Participants entering the optimization/maintenance phase from study ESKETINTRD3003 (Direct Entry) or ESKETINTRD3004 who were ongoing in the Optimization, Maintenance, or Optimization/Maintenance phase, respectively, will have the option to have their current intranasal dosing frequency adjusted at the time of entry into 54135419TRD3008 study and should remain on the selected frequency from week 1 to week 4. A one-time dose change will be permitted at study entry. After 4 weeks, esketamine nasal spray treatment sessions will be individualized to either once weekly or once every other week at the fixed 2-week interval (based on clinical global impression - severity \[CGI-S\] performed at that visit), and every 4 weeks for participants dosed at the 4 week interval. Participants safety will be monitored throughout the study.
Interventions
Open-Label Induction Phase: Participants will self-administer with esketamine nasal spray twice per week for 4 weeks as a flexible dose regimen (56 milligram \[mg\] or 84 mg for those \< 65 years; 28 mg, 56 mg or 84 mg for those \>= 65 years). Participants \>= 65 years old will start at a dose of 28 mg on Day 1. Optimization/Maintenance Phase: Participants entering from studies ESKETINTRD3001 (NCT02417064), ESKETINTRD3002 (NCT02418585) or ESKETINTRD3006 (US sites only) will self-administer esketamine nasal spray (same dose) once weekly. Participants entering from study ESKETINTRD3005 (NCT02422186) will self-administer esketamine nasal spray (28 mg in week 1; 28 or 56 mg in week 2; and 28, 56 or 84 mg in week 3 and 4) once weekly. After Week 4 (starting at Week 5), based on the Investigator's clinical judgment, the dose of esketamine for all participants can be adjusted based upon efficacy and tolerability.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Based on the prior study the participant is entering 54135419TRD3008 from: a) From ESKETINTRD3001 (NCT02417064) or ESKETINTRD3002 (NCT02418585) study: Participant has completed the induction phase and the 2-weeks follow up phase visit; or Participants completed the induction phase and was a responder and study ESKETINTRD3003 is terminated.; b) From ESKETINTRD3003 (NCT02493868) study: (1) Participant relapsed during the maintenance phase; or (2) Participant was in the induction phase of the ESKETINTRD3003 study when the study was terminated and, after completion of the induction phase, was determined to be a responder; or (3) Participant was in the optimization or maintenance phases at the time the study was terminated; or (4) or (5) Participants was in the induction phase and after completion of induction phase was determined to not meet response criteria (1) Participant completed ESKETINTRD3004 study (optimization/maintenance phase); or (2) Participant was in the induction phase of the ESKETINTRD3004 study when the study was terminated and, after completion of the induction phase, was determined to be a responder; or (3) Participant was in the optimization/maintenance phase at the time the study was terminated; (4) Participant was in the induction phase and did not meet criteria for response may be eligible for to be rolled over into 54135419TRD3008. d) From ESKETINTRD3005 (NCT02422186) study: Participant was in the induction phase of the ESKETINTRD3005 study at the time enrollment into the ESKETINTRD3004 study was closed and, after completion of the induction phase, was determined to be a responder or did not meet the criteria for response. e) From ESKETINTRD3006 study (US Study sites only) (1) Participant completed the induction phase and was a responder. * Participant must be medically stable on the basis of physical examination, vital signs, pulse oximetry, and 12-lead Electrocardiogram (ECG) performed predose on the day of the first intranasal treatment session. If there are any abnormalities that are not specified in the inclusion and
Exclusion criteria
, their clinical significance must be determined by the investigator and recorded in the participant's source documents and initialed by the investigator * Participant must be medically stable according to the investigator's judgment and knowledge of the subject's medical stability in the parent study. This determination must be documented. * A woman of childbearing potential must have a negative serum (beta-human chorionic gonadotropin \[b-hCG\]) predose on the day of the first intranasal treatment session * During the study (that is, from the first intranasal treatment session) and for a minimum of 1 spermatogenesis cycle (defined as approximately 90 days) after receiving the last dose of intranasal study medication, a man who is sexually active with a woman of childbearing potential must be practicing a highly effective method of contraception with his female partner c) must agree not to donate sperm.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Blood Oxygen Saturation | IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months | Change from baseline in blood oxygen saturation (predose) were reported. |
| Change From Study Baseline in Computerized Cognitive Battery Domain Score: Groton Maze Learning Test (GMLT) Score | IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months | This battery is a series of computerized cognition tests (detection, identification, one card learning, one back and groton maze learning) designed to measure reaction time, visual learning and memory, and executive function/sequencing. GMLT measures executive function; maze/sequencing test, scored for total number of errors. Total score ranged from 0 to 999 number of errors. Lower score indicated better performance. Higher change from baseline indicated better performance. |
| Change From Study Baseline in Hopkins Verbal Learning Test-Revised (HVLT-R) Score | IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months | The HVLT-R measures performance in verbal memory, learning, and long-term recall in which a list of words is read up to three times. Approximately 20-25 minutes later, a delayed recall trial and a recognition trial are completed. The delayed recall requires free recall of any words remembered. The recognition trial is composed of 24 words, including the 12 target words and 12 false-positives. When scoring the HVLT, the three learning trials are combined to calculate a total recall score (0-36); the delayed recall trial creates the delayed recall score (0-12); the total number of true-positive errors (0-12); and the range of recognition discrimination index is comprised by subtracting the total number of false positives from the total number of true positives. A higher total recall score indicated higher cognition. The range of the recognition discrimination index is -12 to 12. Higher score indicated better performance and higher change from baseline indicated better performance. |
| Percentage of Participants Based on Columbia-Suicide Severity Rating Scale (C-SSRS) Score | IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months | C-SSRS: interview-based instrument to systematically assess suicidal ideation (SI) and behavior, to assess whether participant experienced any of following: completed suicide, suicide attempt (response of yes on actual attempt), preparatory acts toward imminent suicidal behavior (yes on preparatory acts or behavior, aborted attempt or interrupted attempt), suicidal ideation (yes on wish to be dead, non-specific active suicidal thoughts, active SI with methods without intent to act or some intent to act, without or with specific plan and intent), any self-injurious behavior with no suicidal intent (yes on has participant engaged in non-suicidal self-injurious behavior). Here, percentage of participants with \>=1 positive behavior, participants with \>=1 positive ideations; no event were reported. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | IND Phase: up to 4 weeks; OP/MA Phase: up to 78 months | An adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Any AE occurring at or after the initial administration of study intervention up to end of study was considered as treatment-emergent. |
| Change From Baseline in Heart Rate | IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months | Change from baseline (predose) in heart rate were reported. |
| Change From Baseline in Systolic and Diastolic Blood Pressure | IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months | Change from baseline in systolic and diastolic blood pressure were reported. |
| Change From Baseline in Respiratory Rate | IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months | Change from baseline in respiratory rate were reported. |
| Change From Study Baseline in Computerized Cognitive Battery Domain Score: Detection Test (DET) Score | IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months | This battery is a series of computerized cognition tests (detection, identification, one card learning, one back and groton maze learning) designed to measure reaction time, visual learning and memory, and executive function/sequencing. The DET is a measure of psychomotor function and uses a well-validated simple reaction time. In this outcome measure, speed of performance of subjects (calculated as mean of the logarithmic base 10 transformed reaction times) for correct responses was reported. Total score ranged from 2 to 3.3 log 10 milliseconds (msec). Lower score indicated better performance. Higher change from baseline indicated better performance. |
| Change From Study Baseline in Computerized Cognitive Battery Domain Score: Identification Test (IDN) Score | IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months | This battery is a series of computerized cognition tests (detection, identification, one card learning, one back and groton maze learning) designed to measure reaction time, visual learning and memory, and executive function/sequencing. IDN test is a measure of visual attention (choice reaction time) and scored for speed of response (mean of the log10 transformed reaction times for correct responses). Total score ranged from 2 to 3.3 log 10 msec. Lower score indicated better performance. Higher change from baseline indicated better performance. |
| Change From Study Baseline in Computerized Cognitive Battery Domain Score: One Card Learning Test (OCL) Score | IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months | This battery is a series of computerized cognition tests (detection, identification, one card learning, one back and groton maze learning) designed to measure reaction time, visual learning and memory, and executive function/sequencing. OCL test is a measure of visual episodic memory and visual recall test scored using arcsine transformation of the percentage of correct responses (CR). The range for OCL is 0 to 100 percent (%) accuracy; presented as an arcsin transformation, the range is 0 to 1.57. Higher score indicated better performance. Higher change from baseline indicated better performance. |
| Change From Study Baseline in Computerized Cognitive Battery Domain Score: One Back Test (ONB) Score | IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months | The ONB is a measure of working memory and scored for speed of correct response (mean of the log10-transformed reaction times for correct responses). Total score ranged from 2 to 3.54 log10 msec. Lower score indicated better performance. Higher change from baseline indicated better performance. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Participant-Reported Depressive Symptoms Using the Patient Health Questionnaire - 9 (PHQ-9) Total Score | IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months | Change from baseline in PHQ-9 total score were reported. The PHQ-9 was a 9-item, patient-reported outcome measure to assess depressive symptoms. The scale scores each of the 9 symptom domains of the Diagnostic and Statistical Manual of Mental Disorders. Each item was 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 were summed to provide a total score (range of 0 to 27) with higher scores indicating greater severity of depressive symptoms. |
| Change From Baseline in Clinical Global Impression-severity (CGI-S) Score | IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months | Change from baseline in clinical global impression-severity (CGI-S) score were 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. |
| Change From Baseline in Sheehan Disability Scale (SDS) Total Score | IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months | Change from baseline in SDS total score were reported. The SDS, a patient-reported outcome measure, was a 5 item questionnaire which had been widely used and accepted for assessment of functional and associated disability impairment. The first three items assessed 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 were summed to create a total score of 0-30 where a higher score indicated greater impairment. |
| Change From Baseline in Participant-Reported Health-related Quality of Life as Assessed by EuroQol-5 Dimension-5 Level (EQ-5D-5L) Valuation Index Score (VAS) | IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months | Change from baseline in participant-reported health-related quality of life as assessed by EQ-5D-5L VAS was reported. 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-VAS. EQ-VAS self-rating records the respondent's own assessment of his/her overall health status at time of completion, on a scale of 0 (worst health you can imagine) to 100 (best health you can imagine). Positive change in score indicates improvement. |
| Change From Baseline as Assessed by EQ 5D-5L: Sum Score | IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months | EQ-5D-5L consists of EQ-5D-5L descriptive system and EQ visual analogue scale (EQ-VAS). EQ-5D-5L descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each has 5 levels of perceived problems (1-no problem, 2-slight problems, 3-moderate problems, 4-severe problems, 5-extreme problems). Participant selects answer for each of 5 dimensions considering response that best matches his/her health today. Sum score ranges from 0 to 100 where, sum score = (sum of the scores from the 5 dimensions minus 5) \*5. Higher score indicates worst health state. |
| Change From Baseline in Participant- Reported Health Related Quality of Life Using the Quality of Life in Depression Scale (QLDS) | IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months | Change from baseline in participant- reported health related quality of life using the QLDS. The QLDS is a disease-specific validated patient-reported outcome (PRO) measure which assesses the impact that depression has on a participant's quality of life. It is a 34-item self-rated questionnaire which consists of dichotomous response questions, with the response being either True/Not True. Each statement on the QLDS is given a score of 1 or 0. A score of 1 is indicative of adverse quality of life. All item scores are summed to give a total score that ranges from 0 (good quality of life) to 34 (very poor quality of life). A higher score indicates a more severe condition. |
| Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score | IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months | MADRS measures depression severity, detects changes due to AD treatment. It consists of 10 items (evaluate apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, suicidal thoughts), scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), summed for a total possible score of 0 to 60. Higher scores indicate more severe conditions. Negative change in score indicates improvement. Missing data was imputed using last observation carried forward (LOCF) method. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Czechia, Estonia, Finland, France, Germany, Hungary, Lithuania, Malaysia, Mexico, Poland, Slovakia, South Africa, South Korea, Spain, Sweden, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Esketamine Nasal Spray Participants who entered induction phase (IND) from studies NCT02417064, NCT02418585, NCT02493868, NCT02497287, NCT02422186, or ESKETINTRD3006 received esketamine nasal spray twice per week on Day 1 for 4 weeks as a flexible dose regimen (56 milligrams \[mg\] or 84 mg for participants less than \[\<\] 65 years; 28 mg, 56 mg or 84 mg for participants greater than or equal to \[\>=\] 65 years). Participants who entered the optimization and maintenance phase (OP/MA) from the IND phase of study NCT02782104 continued on the same dose of esketamine from the IND phase, weekly. Participants who entered from studies NCT02417064, NCT02418585, NCT02493868, NCT02497287, or ESKETINTRD3006 were administered esketamine nasal spray, 56 mg or 84 mg, once weekly. Participants who entered from study NCT02422186 received esketamine nasal spray (28 mg in Week 1; 28 or 56 mg in Week 2; and 28, 56 or 84 mg in Weeks 3 and 4) once weekly in OP/MP. | 1,148 |
| Total | 1,148 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 74 |
| Overall Study | Death | 8 |
| Overall Study | Induction Day 28 Non Responder | 9 |
| Overall Study | Lack of Efficacy | 61 |
| Overall Study | Lost to Follow-up | 23 |
| Overall Study | Non-Compliance with Study Drug | 2 |
| Overall Study | Other | 215 |
| Overall Study | Pregnancy | 6 |
| Overall Study | Protocol Violation | 7 |
| Overall Study | Withdrawal by Subject | 63 |
Baseline characteristics
| Characteristic | Esketamine Nasal Spray |
|---|---|
| Age, Continuous | 49.6 years STANDARD_DEVIATION 12.28 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 200 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 922 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 26 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants |
| Race/Ethnicity, Customized Asian | 45 Participants |
| Race/Ethnicity, Customized Black or African American | 45 Participants |
| Race/Ethnicity, Customized More than one race | 10 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Other | 29 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 22 Participants |
| Race/Ethnicity, Customized White | 996 Participants |
| Region of Enrollment ARGENTINA | 71 Participants |
| Region of Enrollment AUSTRALIA | 16 Participants |
| Region of Enrollment AUSTRIA | 4 Participants |
| Region of Enrollment BELGIUM | 18 Participants |
| Region of Enrollment BRAZIL | 100 Participants |
| Region of Enrollment BULGARIA | 50 Participants |
| Region of Enrollment CANADA | 15 Participants |
| Region of Enrollment CZECH REPUBLIC | 90 Participants |
| Region of Enrollment ESTONIA | 9 Participants |
| Region of Enrollment FINLAND | 1 Participants |
| Region of Enrollment FRANCE | 23 Participants |
| Region of Enrollment GERMANY | 13 Participants |
| Region of Enrollment HUNGARY | 20 Participants |
| Region of Enrollment ITALY | 8 Participants |
| Region of Enrollment LITHUANIA | 2 Participants |
| Region of Enrollment MALAYSIA | 9 Participants |
| Region of Enrollment MEXICO | 46 Participants |
| Region of Enrollment POLAND | 101 Participants |
| Region of Enrollment SLOVAKIA | 9 Participants |
| Region of Enrollment SOUTH AFRICA | 48 Participants |
| Region of Enrollment SOUTH KOREA | 7 Participants |
| Region of Enrollment SPAIN | 41 Participants |
| Region of Enrollment SWEDEN | 65 Participants |
| Region of Enrollment TAIWAN | 22 Participants |
| Region of Enrollment TURKEY | 24 Participants |
| Region of Enrollment UNITED KINGDOM | 8 Participants |
| Region of Enrollment UNITED STATES | 328 Participants |
| Sex: Female, Male Female | 764 Participants |
| Sex: Female, Male Male | 384 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 458 | 8 / 1,110 |
| other Total, other adverse events | 318 / 458 | 1,010 / 1,110 |
| serious Total, serious adverse events | 5 / 458 | 212 / 1,110 |
Outcome results
Primary
Change From Baseline in Blood Oxygen Saturation
Change from baseline in blood oxygen saturation (predose) were reported.
Time frame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months
Population: Full analysis set included participants who received at least 1 dose of intranasal study medication in this study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Esketamine Nasal Spray (IND Phase) | Change From Baseline in Blood Oxygen Saturation | -0.1 percentage of SpO2 | Standard Deviation 1.54 |
| Esketamine Nasal Spray (OP/MA Phase) | Change From Baseline in Blood Oxygen Saturation | -0.1 percentage of SpO2 | Standard Deviation 1.63 |
Primary
Change From Baseline in Heart Rate
Change from baseline (predose) in heart rate were reported.
Time frame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months
Population: Full analysis set included participants who received at least 1 dose of intranasal study medication in this study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Esketamine Nasal Spray (IND Phase) | Change From Baseline in Heart Rate | 0.4 beats per minute | Standard Deviation 9.52 |
| Esketamine Nasal Spray (OP/MA Phase) | Change From Baseline in Heart Rate | 0.8 beats per minute | Standard Deviation 10.47 |
Primary
Change From Baseline in Respiratory Rate
Change from baseline in respiratory rate were reported.
Time frame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months
Population: Full analysis set included participants who received at least 1 dose of intranasal study medication in this study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Esketamine Nasal Spray (IND Phase) | Change From Baseline in Respiratory Rate | -0.1 breaths per minute | Standard Deviation 2.51 |
| Esketamine Nasal Spray (OP/MA Phase) | Change From Baseline in Respiratory Rate | -0.4 breaths per minute | Standard Deviation 2.83 |
Primary
Change From Baseline in Systolic and Diastolic Blood Pressure
Change from baseline in systolic and diastolic blood pressure were reported.
Time frame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months
Population: Full analysis set included participants who received at least 1 dose of intranasal study medication in this study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Esketamine Nasal Spray (IND Phase) | Change From Baseline in Systolic and Diastolic Blood Pressure | Systolic Blood Pressure | 0.4 Millimeters of mercury (mmHg) | Standard Deviation 10.72 |
| Esketamine Nasal Spray (IND Phase) | Change From Baseline in Systolic and Diastolic Blood Pressure | Diastolic Blood Pressure | 0.3 Millimeters of mercury (mmHg) | Standard Deviation 7.47 |
| Esketamine Nasal Spray (OP/MA Phase) | Change From Baseline in Systolic and Diastolic Blood Pressure | Systolic Blood Pressure | 5.8 Millimeters of mercury (mmHg) | Standard Deviation 12.68 |
| Esketamine Nasal Spray (OP/MA Phase) | Change From Baseline in Systolic and Diastolic Blood Pressure | Diastolic Blood Pressure | 2.7 Millimeters of mercury (mmHg) | Standard Deviation 8.78 |
Primary
Change From Study Baseline in Computerized Cognitive Battery Domain Score: Detection Test (DET) Score
This battery is a series of computerized cognition tests (detection, identification, one card learning, one back and groton maze learning) designed to measure reaction time, visual learning and memory, and executive function/sequencing. The DET is a measure of psychomotor function and uses a well-validated simple reaction time. In this outcome measure, speed of performance of subjects (calculated as mean of the logarithmic base 10 transformed reaction times) for correct responses was reported. Total score ranged from 2 to 3.3 log 10 milliseconds (msec). Lower score indicated better performance. Higher change from baseline indicated better performance.
Time frame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months
Population: All enrolled analysis set included all participants who were eligible to enter this study and received at least 1 dose of intranasal study medication. Here, 'N' (number analyzed) signifies number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Esketamine Nasal Spray (IND Phase) | Change From Study Baseline in Computerized Cognitive Battery Domain Score: Detection Test (DET) Score | 0.0218 log10 msec | Standard Deviation 0.10516 |
| Esketamine Nasal Spray (OP/MA Phase) | Change From Study Baseline in Computerized Cognitive Battery Domain Score: Detection Test (DET) Score | -0.0065 log10 msec | Standard Deviation 0.13526 |
Primary
Change From Study Baseline in Computerized Cognitive Battery Domain Score: Groton Maze Learning Test (GMLT) Score
This battery is a series of computerized cognition tests (detection, identification, one card learning, one back and groton maze learning) designed to measure reaction time, visual learning and memory, and executive function/sequencing. GMLT measures executive function; maze/sequencing test, scored for total number of errors. Total score ranged from 0 to 999 number of errors. Lower score indicated better performance. Higher change from baseline indicated better performance.
Time frame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months
Population: All enrolled analysis set included all participants who were eligible to enter this study and received at least 1 dose of intranasal study medication. Here, 'N' (number analyzed) signifies number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Esketamine Nasal Spray (IND Phase) | Change From Study Baseline in Computerized Cognitive Battery Domain Score: Groton Maze Learning Test (GMLT) Score | 1.5 Number of Errors | Standard Deviation 17.8 |
| Esketamine Nasal Spray (OP/MA Phase) | Change From Study Baseline in Computerized Cognitive Battery Domain Score: Groton Maze Learning Test (GMLT) Score | 5.1 Number of Errors | Standard Deviation 22.52 |
Primary
Change From Study Baseline in Computerized Cognitive Battery Domain Score: Identification Test (IDN) Score
This battery is a series of computerized cognition tests (detection, identification, one card learning, one back and groton maze learning) designed to measure reaction time, visual learning and memory, and executive function/sequencing. IDN test is a measure of visual attention (choice reaction time) and scored for speed of response (mean of the log10 transformed reaction times for correct responses). Total score ranged from 2 to 3.3 log 10 msec. Lower score indicated better performance. Higher change from baseline indicated better performance.
Time frame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months
Population: All enrolled analysis set included all participants who were eligible to enter this study and received at least 1 dose of intranasal study medication. Here, 'N' (number analyzed) signifies number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Esketamine Nasal Spray (IND Phase) | Change From Study Baseline in Computerized Cognitive Battery Domain Score: Identification Test (IDN) Score | 0.0074 log10 msec | Standard Deviation 0.07819 |
| Esketamine Nasal Spray (OP/MA Phase) | Change From Study Baseline in Computerized Cognitive Battery Domain Score: Identification Test (IDN) Score | -0.0185 log10 msec | Standard Deviation 0.09893 |
Primary
Change From Study Baseline in Computerized Cognitive Battery Domain Score: One Back Test (ONB) Score
The ONB is a measure of working memory and scored for speed of correct response (mean of the log10-transformed reaction times for correct responses). Total score ranged from 2 to 3.54 log10 msec. Lower score indicated better performance. Higher change from baseline indicated better performance.
Time frame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months
Population: All enrolled analysis set included all participants who were eligible to enter this study and received at least 1 dose of intranasal study medication. Here, 'N' (number analyzed) signifies number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Esketamine Nasal Spray (IND Phase) | Change From Study Baseline in Computerized Cognitive Battery Domain Score: One Back Test (ONB) Score | 0.0086 log10 msec | Standard Deviation 0.08096 |
| Esketamine Nasal Spray (OP/MA Phase) | Change From Study Baseline in Computerized Cognitive Battery Domain Score: One Back Test (ONB) Score | 0.0198 log10 msec | Standard Deviation 0.10329 |
Primary
Change From Study Baseline in Computerized Cognitive Battery Domain Score: One Card Learning Test (OCL) Score
This battery is a series of computerized cognition tests (detection, identification, one card learning, one back and groton maze learning) designed to measure reaction time, visual learning and memory, and executive function/sequencing. OCL test is a measure of visual episodic memory and visual recall test scored using arcsine transformation of the percentage of correct responses (CR). The range for OCL is 0 to 100 percent (%) accuracy; presented as an arcsin transformation, the range is 0 to 1.57. Higher score indicated better performance. Higher change from baseline indicated better performance.
Time frame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months
Population: All enrolled analysis set included all participants who were eligible to enter this study and received at least 1 dose of intranasal study medication. Here, 'N' (number analyzed) signifies number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Esketamine Nasal Spray (IND Phase) | Change From Study Baseline in Computerized Cognitive Battery Domain Score: One Card Learning Test (OCL) Score | 0.0170 Arcsine (sqrt of percentage of CR) | Standard Deviation 0.12356 |
| Esketamine Nasal Spray (OP/MA Phase) | Change From Study Baseline in Computerized Cognitive Battery Domain Score: One Card Learning Test (OCL) Score | 0.0397 Arcsine (sqrt of percentage of CR) | Standard Deviation 0.15364 |
Primary
Change From Study Baseline in Hopkins Verbal Learning Test-Revised (HVLT-R) Score
The HVLT-R measures performance in verbal memory, learning, and long-term recall in which a list of words is read up to three times. Approximately 20-25 minutes later, a delayed recall trial and a recognition trial are completed. The delayed recall requires free recall of any words remembered. The recognition trial is composed of 24 words, including the 12 target words and 12 false-positives. When scoring the HVLT, the three learning trials are combined to calculate a total recall score (0-36); the delayed recall trial creates the delayed recall score (0-12); the total number of true-positive errors (0-12); and the range of recognition discrimination index is comprised by subtracting the total number of false positives from the total number of true positives. A higher total recall score indicated higher cognition. The range of the recognition discrimination index is -12 to 12. Higher score indicated better performance and higher change from baseline indicated better performance.
Time frame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months
Population: All enrolled analysis set included all participants who were eligible to enter this study and received at least 1 dose of intranasal study medication. Here, 'N' (number analyzed) signifies number of participants analyzed for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Esketamine Nasal Spray (IND Phase) | Change From Study Baseline in Hopkins Verbal Learning Test-Revised (HVLT-R) Score | Total Recall | -0.1 score on a scale | Standard Deviation 4.05 |
| Esketamine Nasal Spray (IND Phase) | Change From Study Baseline in Hopkins Verbal Learning Test-Revised (HVLT-R) Score | Delayed Recall | 0.3 score on a scale | Standard Deviation 3.81 |
| Esketamine Nasal Spray (IND Phase) | Change From Study Baseline in Hopkins Verbal Learning Test-Revised (HVLT-R) Score | Total Number of True Positives | 0.1 score on a scale | Standard Deviation 2.54 |
| Esketamine Nasal Spray (IND Phase) | Change From Study Baseline in Hopkins Verbal Learning Test-Revised (HVLT-R) Score | Recognition Discrimination Index | -0.1 score on a scale | Standard Deviation 2.88 |
| Esketamine Nasal Spray (OP/MA Phase) | Change From Study Baseline in Hopkins Verbal Learning Test-Revised (HVLT-R) Score | Recognition Discrimination Index | -0.1 score on a scale | Standard Deviation 3.1 |
| Esketamine Nasal Spray (OP/MA Phase) | Change From Study Baseline in Hopkins Verbal Learning Test-Revised (HVLT-R) Score | Total Recall | 0.8 score on a scale | Standard Deviation 5.05 |
| Esketamine Nasal Spray (OP/MA Phase) | Change From Study Baseline in Hopkins Verbal Learning Test-Revised (HVLT-R) Score | Total Number of True Positives | -0.0 score on a scale | Standard Deviation 2.7 |
| Esketamine Nasal Spray (OP/MA Phase) | Change From Study Baseline in Hopkins Verbal Learning Test-Revised (HVLT-R) Score | Delayed Recall | 0.3 score on a scale | Standard Deviation 2.03 |
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Any AE occurring at or after the initial administration of study intervention up to end of study was considered as treatment-emergent.
Time frame: IND Phase: up to 4 weeks; OP/MA Phase: up to 78 months
Population: All enrolled analysis set included all participants who were eligible to enter this study and received at least 1 dose of intranasal study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Esketamine Nasal Spray (IND Phase) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 346 Participants |
| Esketamine Nasal Spray (OP/MA Phase) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 1052 Participants |
Primary
Percentage of Participants Based on Columbia-Suicide Severity Rating Scale (C-SSRS) Score
C-SSRS: interview-based instrument to systematically assess suicidal ideation (SI) and behavior, to assess whether participant experienced any of following: completed suicide, suicide attempt (response of yes on actual attempt), preparatory acts toward imminent suicidal behavior (yes on preparatory acts or behavior, aborted attempt or interrupted attempt), suicidal ideation (yes on wish to be dead, non-specific active suicidal thoughts, active SI with methods without intent to act or some intent to act, without or with specific plan and intent), any self-injurious behavior with no suicidal intent (yes on has participant engaged in non-suicidal self-injurious behavior). Here, percentage of participants with \>=1 positive behavior, participants with \>=1 positive ideations; no event were reported.
Time frame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months
Population: All enrolled analysis set included all participants who were eligible to enter this study and received at least 1 dose of intranasal study medication. Here, 'N' (number analyzed) signifies number of participants analyzed for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Esketamine Nasal Spray (IND Phase) | Percentage of Participants Based on Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Baseline: No Event | 79.8 Percentage of participants |
| Esketamine Nasal Spray (IND Phase) | Percentage of Participants Based on Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Baseline: Suicidal ideation | 20.2 Percentage of participants |
| Esketamine Nasal Spray (IND Phase) | Percentage of Participants Based on Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Baseline: Suicidal behavior | 0 Percentage of participants |
| Esketamine Nasal Spray (IND Phase) | Percentage of Participants Based on Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Most Severe Post Baseline: No Event | 77.4 Percentage of participants |
| Esketamine Nasal Spray (IND Phase) | Percentage of Participants Based on Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Most Severe Post Baseline: Suicidal ideation | 22.6 Percentage of participants |
| Esketamine Nasal Spray (IND Phase) | Percentage of Participants Based on Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Most Severe Post Baseline: Suicidal behavior | 0 Percentage of participants |
| Esketamine Nasal Spray (OP/MA Phase) | Percentage of Participants Based on Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Most Severe Post Baseline: Suicidal ideation | 27.8 Percentage of participants |
| Esketamine Nasal Spray (OP/MA Phase) | Percentage of Participants Based on Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Baseline: No Event | 94.8 Percentage of participants |
| Esketamine Nasal Spray (OP/MA Phase) | Percentage of Participants Based on Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Most Severe Post Baseline: No Event | 70.2 Percentage of participants |
| Esketamine Nasal Spray (OP/MA Phase) | Percentage of Participants Based on Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Baseline: Suicidal ideation | 5.2 Percentage of participants |
| Esketamine Nasal Spray (OP/MA Phase) | Percentage of Participants Based on Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Most Severe Post Baseline: Suicidal behavior | 2.0 Percentage of participants |
| Esketamine Nasal Spray (OP/MA Phase) | Percentage of Participants Based on Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Baseline: Suicidal behavior | 0 Percentage of participants |
Secondary
Change From Baseline as Assessed by EQ 5D-5L: Sum Score
EQ-5D-5L consists of EQ-5D-5L descriptive system and EQ visual analogue scale (EQ-VAS). EQ-5D-5L descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each has 5 levels of perceived problems (1-no problem, 2-slight problems, 3-moderate problems, 4-severe problems, 5-extreme problems). Participant selects answer for each of 5 dimensions considering response that best matches his/her health today. Sum score ranges from 0 to 100 where, sum score = (sum of the scores from the 5 dimensions minus 5) \*5. Higher score indicates worst health state.
Time frame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months
Population: Full analysis set included all participants who received at least 1 dose of intranasal study medication in this study. Here, 'N' (number analyzed) signifies number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Esketamine Nasal Spray (IND Phase) | Change From Baseline as Assessed by EQ 5D-5L: Sum Score | -10.4 score on a scale | Standard Deviation 12.81 |
| Esketamine Nasal Spray (OP/MA Phase) | Change From Baseline as Assessed by EQ 5D-5L: Sum Score | 2.9 score on a scale | Standard Deviation 15.88 |
Secondary
Change From Baseline in Clinical Global Impression-severity (CGI-S) Score
Change from baseline in clinical global impression-severity (CGI-S) score were 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.
Time frame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months
Population: Full analysis set included all participants who received at least 1 dose of intranasal study medication in this study. Here, 'N' (number analyzed) signifies number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Esketamine Nasal Spray (IND Phase) | Change From Baseline in Clinical Global Impression-severity (CGI-S) Score | -1.0 score on a scale |
| Esketamine Nasal Spray (OP/MA Phase) | Change From Baseline in Clinical Global Impression-severity (CGI-S) Score | 0.0 score on a scale |
Secondary
Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score
MADRS measures depression severity, detects changes due to AD treatment. It consists of 10 items (evaluate apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, suicidal thoughts), scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), summed for a total possible score of 0 to 60. Higher scores indicate more severe conditions. Negative change in score indicates improvement. Missing data was imputed using last observation carried forward (LOCF) method.
Time frame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months
Population: Full analysis set included all participants who received at least 1 dose of intranasal study medication in this study. Here, 'N' (number analyzed) signifies number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Esketamine Nasal Spray (IND Phase) | Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score | -12.8 score on a Scale | Standard Deviation 9.73 |
| Esketamine Nasal Spray (OP/MA Phase) | Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score | 0.2 score on a Scale | Standard Deviation 9.93 |
Secondary
Change From Baseline in Participant-Reported Depressive Symptoms Using the Patient Health Questionnaire - 9 (PHQ-9) Total Score
Change from baseline in PHQ-9 total score were reported. The PHQ-9 was a 9-item, patient-reported outcome measure to assess depressive symptoms. The scale scores each of the 9 symptom domains of the Diagnostic and Statistical Manual of Mental Disorders. Each item was 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 were summed to provide a total score (range of 0 to 27) with higher scores indicating greater severity of depressive symptoms.
Time frame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months
Population: Full analysis set included all participants who received at least 1 dose of intranasal study medication in this study. Here, 'N' (number analyzed) signifies number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Esketamine Nasal Spray (IND Phase) | Change From Baseline in Participant-Reported Depressive Symptoms Using the Patient Health Questionnaire - 9 (PHQ-9) Total Score | -5.8 score on a scale | Standard Deviation 5.84 |
| Esketamine Nasal Spray (OP/MA Phase) | Change From Baseline in Participant-Reported Depressive Symptoms Using the Patient Health Questionnaire - 9 (PHQ-9) Total Score | 0.6 score on a scale | Standard Deviation 6.22 |
Secondary
Change From Baseline in Participant-Reported Health-related Quality of Life as Assessed by EuroQol-5 Dimension-5 Level (EQ-5D-5L) Valuation Index Score (VAS)
Change from baseline in participant-reported health-related quality of life as assessed by EQ-5D-5L VAS was reported. 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-VAS. EQ-VAS self-rating records the respondent's own assessment of his/her overall health status at time of completion, on a scale of 0 (worst health you can imagine) to 100 (best health you can imagine). Positive change in score indicates improvement.
Time frame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months
Population: Full analysis set included who received at least 1 dose of intranasal study medication in this study. Here, 'N' (number analyzed) signifies number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Esketamine Nasal Spray (IND Phase) | Change From Baseline in Participant-Reported Health-related Quality of Life as Assessed by EuroQol-5 Dimension-5 Level (EQ-5D-5L) Valuation Index Score (VAS) | 13.0 score on a scale | Standard Deviation 18.05 |
| Esketamine Nasal Spray (OP/MA Phase) | Change From Baseline in Participant-Reported Health-related Quality of Life as Assessed by EuroQol-5 Dimension-5 Level (EQ-5D-5L) Valuation Index Score (VAS) | 0.7 score on a scale | Standard Deviation 18.95 |
Secondary
Change From Baseline in Participant- Reported Health Related Quality of Life Using the Quality of Life in Depression Scale (QLDS)
Change from baseline in participant- reported health related quality of life using the QLDS. The QLDS is a disease-specific validated patient-reported outcome (PRO) measure which assesses the impact that depression has on a participant's quality of life. It is a 34-item self-rated questionnaire which consists of dichotomous response questions, with the response being either True/Not True. Each statement on the QLDS is given a score of 1 or 0. A score of 1 is indicative of adverse quality of life. All item scores are summed to give a total score that ranges from 0 (good quality of life) to 34 (very poor quality of life). A higher score indicates a more severe condition.
Time frame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months
Population: Full analysis set included who received at least 1 dose of intranasal study medication in this study. Here, 'N' (number analyzed) signifies number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Esketamine Nasal Spray (IND Phase) | Change From Baseline in Participant- Reported Health Related Quality of Life Using the Quality of Life in Depression Scale (QLDS) | -8.2 score on a scale | Standard Deviation 8.47 |
| Esketamine Nasal Spray (OP/MA Phase) | Change From Baseline in Participant- Reported Health Related Quality of Life Using the Quality of Life in Depression Scale (QLDS) | 0.1 score on a scale | Standard Deviation 9.47 |
Secondary
Change From Baseline in Sheehan Disability Scale (SDS) Total Score
Change from baseline in SDS total score were reported. The SDS, a patient-reported outcome measure, was a 5 item questionnaire which had been widely used and accepted for assessment of functional and associated disability impairment. The first three items assessed 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 were summed to create a total score of 0-30 where a higher score indicated greater impairment.
Time frame: IND Phase: Baseline up to 4 weeks; OP/MA Phase: Baseline up to 78 months
Population: Full analysis set included all participants who received at least 1 dose of intranasal study medication in this study. Here, 'N' (number analyzed) signifies number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Esketamine Nasal Spray (IND Phase) | Change From Baseline in Sheehan Disability Scale (SDS) Total Score | -6.4 score on a scale | Standard Deviation 7.13 |
| Esketamine Nasal Spray (OP/MA Phase) | Change From Baseline in Sheehan Disability Scale (SDS) Total Score | -0.1 score on a scale | Standard Deviation 8.35 |