Clinical Trial Results:
Open-label Long-Term Extension Study for Participants With Treatment-Resistant Major Depressive Disorder Who are Continuing Esketamine Nasal Spray Treatment From Study 54135419TRD3013
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Summary
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EudraCT number |
2020-004291-18 |
Trial protocol |
DE BE CZ HU PL BG FI GR |
Global end of trial date |
22 Jul 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
03 Aug 2025
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First version publication date |
03 Aug 2025
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
54135419TRD4010
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04829318 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Janssen-Cilag International NV
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Sponsor organisation address |
Turnhoutseweg 30, Beerse, Belgium, B-2340
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Public contact |
Clinical Registry Group, Janssen-Cilag International NV, ClinicalTrialsEU@its.jnj.com
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Scientific contact |
Clinical Registry Group, Janssen-Cilag International NV, ClinicalTrialsEU@its.jnj.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
24 Sep 2024
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
22 Jul 2024
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Main objective of the trial was to assess the long-term safety and tolerability of esketamine nasal spray in combination with a selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI) in subjects who have completed 32 weeks of esketamine nasal spray treatment in Study 54135419TRD3013.
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Protection of trial subjects |
This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practices and applicable regulatory requirements.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
26 Apr 2021
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Argentina: 24
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Country: Number of subjects enrolled |
Belgium: 1
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Country: Number of subjects enrolled |
Bulgaria: 9
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Country: Number of subjects enrolled |
Czechia: 25
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Country: Number of subjects enrolled |
Finland: 1
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Country: Number of subjects enrolled |
Germany: 19
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Country: Number of subjects enrolled |
Greece: 3
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Country: Number of subjects enrolled |
Hungary: 3
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Country: Number of subjects enrolled |
Malaysia: 4
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Country: Number of subjects enrolled |
Poland: 69
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Country: Number of subjects enrolled |
Korea, Republic of: 6
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Country: Number of subjects enrolled |
South Africa: 6
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Country: Number of subjects enrolled |
Taiwan: 7
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Country: Number of subjects enrolled |
Türkiye: 6
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Worldwide total number of subjects |
183
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EEA total number of subjects |
130
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
174
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From 65 to 84 years |
9
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85 years and over |
0
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Recruitment
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Recruitment details |
A total of 183 subjects who completed the maintenance phase (Week 32) of study 54135419TRD3013 were enrolled and treated in this study. | ||||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
A total of 183 subjects who completed the maintenance phase (Week 32) of study 54135419TRD3013 were enrolled and treated in this study. | ||||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||||||
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Arms
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Arm title
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Esketamine nasal spray + Oral Antidepressant (AD) | ||||||||||||||||||||||||||||||||
Arm description |
Subjects (who received esketamine nasal spray in study 54135419TRD3013 through Week 30 [every 2 weeks] or Week 31 [once weekly], and completed the maintenance phase at Week 32) received flexible dose of esketamine nasal spray 28 milligrams (mg) (1 spray per nostril at 0 minute), 56 mg (1 spray per nostril at 0 and 5 minutes) or 84 mg (1 spray per nostril at 0, 5 and 10 minutes) once weekly or every 2 weeks from Day 1 (Week 32 visit of Study 54135419TRD3013 until week 104 along with oral AD, serotonin-norepinephrine reuptake inhibitor/selective serotonin reuptake inhibitor (SSRI/SNRI) in this long-term extension (LTE) study. Time 0 minute signified time of first esketamine nasal spray administration to 1 nostril. Esketamine nasal devices contained a total of 28 mg esketamine per device (2 sprays). Only one device was used at a timepoint. | ||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Esketamine nasal spray
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Investigational medicinal product code |
JNJ-54135419
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Other name |
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Pharmaceutical forms |
Nasal spray
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Routes of administration |
Nasal use
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Dosage and administration details |
Subjects received flexible dose of esketamine nasal spray 28 mg, 56 mg or 84 mg once weekly or every 2 weeks from Day 1 up to Week 104.
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| Notes [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: Only reported subjects were planned to be included in this milestone. [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: Only reported subjects were planned to be included in this milestone. [3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: Only reported subjects were planned to be included in this milestone. |
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Baseline characteristics reporting groups
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Reporting group title |
Overall Study
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Reporting group description |
Subjects (who received esketamine nasal spray in study 54135419TRD3013 through Week 30 [every 2 weeks] or Week 31 [once weekly], and completed the maintenance phase at Week 32) received flexible dose of esketamine nasal spray 28 milligrams (mg) (1 spray per nostril at 0 minute), 56 mg (1 spray per nostril at 0 and 5 minutes) or 84 mg (1 spray per nostril at 0, 5 and 10 minutes) once weekly or every 2 weeks from Day 1 (Week 32 visit of Study 54135419TRD3013 until week 104 along with oral AD, serotonin-norepinephrine reuptake inhibitor/selective serotonin reuptake inhibitor (SSRI/SNRI) in this long-term extension (LTE) study. Time 0 minute signified time of first esketamine nasal spray administration to 1 nostril. Esketamine nasal devices contained a total of 28 mg esketamine per device (2 sprays). Only one device was used at a timepoint. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Esketamine nasal spray + Oral Antidepressant (AD)
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Reporting group description |
Subjects (who received esketamine nasal spray in study 54135419TRD3013 through Week 30 [every 2 weeks] or Week 31 [once weekly], and completed the maintenance phase at Week 32) received flexible dose of esketamine nasal spray 28 milligrams (mg) (1 spray per nostril at 0 minute), 56 mg (1 spray per nostril at 0 and 5 minutes) or 84 mg (1 spray per nostril at 0, 5 and 10 minutes) once weekly or every 2 weeks from Day 1 (Week 32 visit of Study 54135419TRD3013 until week 104 along with oral AD, serotonin-norepinephrine reuptake inhibitor/selective serotonin reuptake inhibitor (SSRI/SNRI) in this long-term extension (LTE) study. Time 0 minute signified time of first esketamine nasal spray administration to 1 nostril. Esketamine nasal devices contained a total of 28 mg esketamine per device (2 sprays). Only one device was used at a timepoint. | ||
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End point title |
Incidence Rate of Treatment-emergent Adverse Events (TEAEs) [1] | ||||||||
End point description |
Incidence rate of TEAEs were reported. AE Incidence rate was defined as incidence rate per 100 patient-months = (number of subjects with AE divided by sum of days at risk for AE) * 100*365.25/12. An AE was any untoward medical occurrence in a clinical study subject administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Any AE occurring at or after the initial administration of study intervention up to 30 days after last dose in Study 54135419TRD4010 was considered to be treatment emergent. TEAEs included both serious and non-serious adverse events. Safety analysis set was used.
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End point type |
Primary
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End point timeframe |
From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No inferential statistics was done. Only descriptive statistics was performed. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects with Treatment-emergent Adverse Events (TEAEs) [2] | ||||||||
End point description |
Percentage of subjects with TEAEs were reported. An AE was any untoward medical occurrence in a clinical study subject administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Any AE occurring at or after the initial administration of study intervention up to 30 days after last dose in Study 54135419TRD4010 was considered to be treatment emergent. TEAEs included both serious and non-serious adverse events. Safety analysis set included all subjects who received at least 1 dose of esketamine anytime during the 54135419TRD4010 study.
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End point type |
Primary
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End point timeframe |
From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No inferential statistics was done. Only descriptive statistics was performed. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects with Treatment-emergent AEs of Special interest (AESIs) [3] | ||||||||||||||||||
End point description |
An AE was any untoward medical occurrence in a clinical study subject administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with intervention. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Any AE occurring at or after the initial administration of study intervention up to 30 days after last dose in Study 54135419TRD4010 was considered to be treatment emergent. TEAEs included both serious and non-serious AEs. AEs of special interest were separately grouped by categories sedation, dissociation, suicidality, suggestive of abuse potential, cystitis and hepatic impairment. Safety analysis set was used.
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End point type |
Primary
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End point timeframe |
From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No inferential statistics was done. Only descriptive statistics was performed. |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Percentage of of Subjects with TEAEs Leading to Death [4] | ||||||||
End point description |
Percentage of subjects with TEAEs leading to death were reported. An AE was any untoward medical occurrence in a clinical study subject administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Any AE occurring at or after the initial administration of study intervention up to 30 days after last dose in Study 54135419TRD4010 was considered to be treatment emergent. TEAEs included both serious and non-serious adverse events. Safety analysis set included all subjects who received at least 1 dose of esketamine anytime during the 54135419TRD4010 study.
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End point type |
Primary
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End point timeframe |
From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No inferential statistics was done. Only descriptive statistics was performed. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects with Treatment-emergent Serious Adverse Events (TESAEs) [5] | ||||||||
End point description |
Percentage of subjects with TESAEs were reported. An AE was any untoward medical occurrence in a clinical study subject administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Any AE occurring at or after the initial administration of study intervention up to 30 days after last dose in Study 54135419TRD4010 was considered to be treatment emergent. Safety analysis set included all subjects who received at least 1 dose of esketamine anytime during the 54135419TRD4010 study.
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End point type |
Primary
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End point timeframe |
From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)
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| Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No inferential statistics was done. Only descriptive statistics was performed. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Incidence Rate of TEAEs Leading to Death [6] | ||||||||
End point description |
Incidence rate of TEAEs leading to death were reported. AE Incidence rate was defined as incidence rate per 100 patient-months = (number of subjects with AE divided by sum of days at risk for AE) * 100*365.25/12. An AE was any untoward medical occurrence in a clinical study subject administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Any AE occurring at or after the initial administration of study intervention up to 30 days after last dose in Study 54135419TRD4010 was considered to be treatment emergent. TEAEs included both serious and non-serious adverse events. Safety analysis set was used.
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End point type |
Primary
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End point timeframe |
From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)
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| Notes [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No inferential statistics was done. Only descriptive statistics was performed. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Incidence Rate of Treatment-emergent Serious Adverse Events (TESAEs) [7] | ||||||||
End point description |
Incidence rate of with TESAEs were reported. AE Incidence rate was defined as incidence rate per 100 patient-months = (number of subjects with AE divided by sum of days at risk for AE) * 100*365.25/12. An AE was any untoward medical occurrence in a clinical study subject administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Any AE occurring at or after the initial administration of study intervention up to 30 days after last dose in Study 54135419TRD4010 was considered to be treatment emergent. Safety analysis set was used.
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End point type |
Primary
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End point timeframe |
From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)
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| Notes [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No inferential statistics was done. Only descriptive statistics was performed. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Incidence Rate of Treatment-emergent AEs of Special interest (AESIs) [8] | ||||||||||||||||||
End point description |
AE Incidence rate: incidence rate per 100 patient-months=(number of subjects with AE divided by sum of days at risk for AE) * 100*365.25/12. AE: any untoward medical occurrence in clinical study subject administered a medicinal (investigational or non investigational) drug. An AE does not necessarily have a causal relationship with drug. SAE: AE resulting following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Any AE occurring at or after the initial drug administration up to 30 days after last dose in Study 54135419TRD4010 was considered to be treatment emergent. TEAEs included both serious and non-SAEs. AEs of special interest were grouped as categories sedation, dissociation, suicidality, suggestive of abuse potential, cystitis and hepatic impairment. Safety analysis set included was used.
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End point type |
Primary
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End point timeframe |
From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)
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| Notes [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No inferential statistics was done. Only descriptive statistics was performed. |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Number of Subjects with Suicidal Ideation and Behavior in Study 54135419TRD4010 as Assessed by Columbia-suicide Severity Rating Scale (C-SSRS) Score [9] | ||||||||||||
End point description |
C-SSRS score was defined as an assessment tool that evaluated suicidal ideation and behavior. Suicidal ideation (5 items): wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intention to act, active suicidal ideation with some intent to act without specific plan, and active suicidal ideation with specific plan and intent. Suicidal behavior (5 items): preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt (non-fatal), and suicide. The total score from 10 categories was summarized into 3 broad categories: No suicidal ideation or behavior (0), Suicidal ideation (1 to 5), Suicidal behavior (6 to 10). Total score ranged from 1 to 10. Higher scores indicated more severe suicidal ideation and behavior. Safety analysis set was analysed.
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End point type |
Primary
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End point timeframe |
Baseline (Day 1 of Study 54135419TRD3013) up to Week 104 of Study 54135419TRD4010
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| Notes [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No inferential statistics was done. Only descriptive statistics was performed. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Subjects with No Relapse and Without Discontinuation Until the end of the Prospective Observation Period at Week 104 | ||||||||
End point description |
Relapse was defined by any of the following: a) Worsening of depressive symptoms as indicated by Montgomery-Asberg Depression Rating Scale (MADRS) total score >=22 confirmed by 1 additional assessment of MADRS total score >=22 within the next 5 to 31 days. b) Any psychiatric hospitalization for: 1) worsening of depression, 2) suicide prevention or due to a suicide attempt for any of these events. c) Suicide attempt, completed suicide, or any other clinically relevant event determined per investigator's clinical judgment to be indicative of relapse of depressive illness, but for which subject was not hospitalized. MADRS scale consisted of 10 items, 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 0 to 60. Higher scores represented a more severe condition. Analysis population included subjects in Remission (MADRS total score of <=10.) at any time point during Study 54135419TRD3013.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1 of Study 54135419TRD3013) up to Week 104 of 54135419TRD4010
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| No statistical analyses for this end point | |||||||||
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End point title |
Change from Baseline of Study 54135419TRD3013 in Clinician-rated Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Change from Baseline of Study 54135419TRD3013 in Clinician-rated MADRS total score were reported. MADRS was a clinician-rated scale designed to measure depression severity and to detect changes due to antidepressant treatment. The scale consists of 10 items , scored from 0 (item is not present or normal) to 6 (severe or continuous presence of symptoms), summed up for a total possible score range of 0 to 60. Higher scores represented a more severe condition. The MADRS evaluated reported sadness, apparent sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Efficacy analysis set included all subjects who received at least 1 dose of esketamine anytime during the 54135419TRD4010 study. Here "N" (Number of subjects analysed) signifies subjects evaluable for this endpoint and "n" signifies subjects analysed at specified timepoints.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1 of Study 54135419TRD3013) up to weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, and 104 of study 54135419TRD4010
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Change from Baseline of Study 54135419TRD3013 in Clinician-rated Montgomery-Asberg Depression Rating Scale (MADRS) Score Individual Items | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Change from Baseline of Study 54135419TRD3013 in Clinician-rated MADRS Score Individual Items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts) were reported. MADRS was a clinician-rated scale designed to measure depression severity and to detect changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of the symptoms), summed up for a total possible score range of 0 to 60. Higher scores represent a more severe condition. Efficacy analysis set included all subjects who received at least 1 dose of esketamine anytime during the 54135419TRD4010 study. Here "N" (Number of subjects analysed) signifies subjects evaluable for this endpoint and "n" signifies subjects analysed at specified timepoints.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1 of Study 54135419TRD3013) up to weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, and 104 of study 54135419TRD4010
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Change from Baseline of Study 54135419TRD3013 in Clinical Global Impression -severity (CGI-S) Scale Score | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Change from Baseline of Study 54135419TRD3013 in CGI-S scale score were reported. The CGI-S provided an overall clinician-determined summary measure of the severity of the subject's illness that took into account all available information, including knowledge of the subject's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the subject's ability to function. The CGI-S evaluated the severity of psychopathology on a scale of 1 to 7: where, 1 = normal (not ill); 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; 7 = among the most extremely ill subjects. Negative change in score indicated improvement. Subjects with a score of zero were considered missing. Efficacy analysis set were used. Here "N" (Number of subjects analysed) signifies subjects evaluable for this endpoint and "n" signifies subjects analysed at specified timepoints.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1 of Study 54135419TRD3013) up to weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, and 104 of study 54135419TRD4010
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Change from Baseline of Study 54135419TRD3013 in Patient Health Questionnaire (PHQ) 9-item Total Score | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Change from Baseline of Study 54135419TRD3013 in PHQ 9-item total score were reported. The PHQ-9 was a validated 9-item, patient-reported outcome (PRO) measure to assess depressive symptoms. 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 subject's item responses were summed to a total score with a range of 0 to 27. Higher scores indicated greater severity of depressive symptoms. Efficacy analysis set was used. Here "N" (Number of subjects analysed) signifies subjects evaluable for this endpoint and "n" signifies subjects analysed at specified timepoints.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1 of Study 54135419TRD3013) up to weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, and 104 of study 54135419TRD4010
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Change from Baseline of Study 54135419TRD3013 in European Quality of Life (EuroQol) 5 Dimension 5-Level (EQ-5D-5L): Health status index | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Change from baseline of Study 54135419TRD3013 in EQ-5D-5LQuestionnaire Score: health status index was reported. The EQ-5D-5L descriptive system comprised the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each of the 5 dimensions were divided into 5 levels of perceived problems (level 1 = no problem, level 2 = slight problems, level 3 = moderate problems, level 4 = severe problems, level 5 = extreme problems). The subject selected an answer for each of the 5 dimensions considering a response that best matched subject's health "today." Responses were used to generate health status index ranged from 0.148 to 0.949, anchored at 0 (dead) and 1 (full health). Positive change in score indicated improvement. Efficacy analysis set was used. Here "N" (Number of subjects analysed) signifies subjects evaluable for this endpoint and "n" signifies subjects analysed at specified timepoints.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1 of Study 54135419TRD3013) up to weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, and 104 of study 54135419TRD4010
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Change from Baseline of Study 54135419TRD3013 in European Quality of Life (EuroQol) 5 Dimension 5-Level (EQ-5D-5L): Visual Analogue Scale (VAS) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Change from baseline of Study 54135419TRD3013 in EQ-5D-5L: visual analogue scale were reported. EQ-VAS self-rating recorded the subject'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 indicated improvement. Efficacy analysis set included all subjects who received at least 1 dose of esketamine anytime during the 54135419TRD4010 study. Here "N" (Number of subjects analysed) signifies subjects evaluable for this endpoint and "n" signifies subjects analysed at specified timepoints.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1 of Study 54135419TRD3013) up to weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, and 104 of study 54135419TRD4010
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)
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Adverse event reporting additional description |
Safety analysis set included all subjects who received at least 1 dose of esketamine anytime during the 54135419TRD4010 study.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
27.0
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Reporting groups
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Reporting group title |
Esketamine + Oral AD
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Reporting group description |
Subjects (who received esketamine nasal spray in study 54135419TRD3013 through Week 30 [every 2 weeks] or Week 31 [once weekly],and completed the maintenance phase at Week 32) received flexible dose of esketamine nasal spray 28 milligrams (mg) (1 spray per nostril at 0 minute), 56 mg (1 spray per nostril at 0 and 5 minutes) or 84 mg (1 spray per nostril at 0, 5 and 105 minutes) once weekly or every 2 weeks from Day 1 (Week 32 visit of Study 54135419TRD3013 until week 104 along with oral AD, serotonin-norepinephrine reuptake inhibitor/selective serotonin reuptake inhibitor (SSRI/SNRI) in this long-term extension (LTE) study. Time 0 minute signified time of first esketamine nasal spray administration to 1 nostril. Esketamine nasal devices contained a total of 28 mg esketamine per device (2 sprays). Only one device was used at a timepoint. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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02 Sep 2022 |
The purpose of the amendment was to indicate that the bicarbonate assay (one of the protocol required clinical laboratory safety tests) was optional, to reduce patient burden. In addition, the window during which the additional assessment of MADRS total score were evaluated to confirm relapse was widened (from ‘14 to 28 days’ to ‘5 to 31 days') to allow greater patient flexibility with undertaking this additional assessment and to align with the parent study (54135419TRD3013) and a previous relapse prevention study. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
