Open-label Long-Term Extension Study for Participants With Treatment-Resistant Major Depressive Disorder Who Are Continuing Esketamine Nasal Spray Treatment From Study 54135419TRD3013
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 183
- 试验地点
- 58
- 主要终点
- Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
The primary purpose of this study is 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 participants who have completed 32 weeks of esketamine nasal spray treatment in Study 54135419TRD3013 (NCT04338321).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Completed the maintenance phase (Week 32) of Study 54135419TRD3013 (NCT04338321) and had esketamine nasal spray in combination with continuing selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI) administered through Week 30 (every 2 week dosing) or Week 31 (once weekly dosing) of Study 54135419TRD3013, and continues to be willing to be treated with esketamine nasal spray
- •Must, in the opinion of the investigator, be benefiting from continuation of esketamine nasal spray in combination with their current SSRI/SNRI based on efficacy and tolerability assessed on Day 1 of this study
- •Must be medically stable based on the investigator's judgment
- •A woman of childbearing potential must have a negative urine pregnancy test on Day 1
- •Male participants who are sexually active with a woman of childbearing potential must agree to the following during the intervention period and for at least 1 spermatogenesis cycle (defined as approximately 90 days) after receiving the last dose of study intervention (that is, esketamine nasal spray), must fulfill the following criteria: must be practicing a highly effective method of contraception with his female partner, must use a condom if his partner is pregnant, and must agree not to donate sperm
排除标准
- •Has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (example, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments
- •Completed Study 54135419TRD3013 while presenting adverse events deemed clinically relevant by the investigator, and which may interfere with safety and well-being of the participant
- •Has developed during participation in Study 54135419TRD3013 any of the following cardiovascular-related conditions where an increase in blood pressure or intracranial pressure poses a serious risk: cerebrovascular disease following stroke or transient ischemic attack, aneurysmal vascular disease (including intracranial, thoracic, or abdominal aorta, or peripheral arterial vessels), intracerebral hemorrhage, coronary artery disease following myocardial infarction, unstable angina, or revascularization procedure (example, coronary angioplasty or bypass graft surgery), uncontrolled brady- or tachyarrhythmias that lead to hemodynamic instability, hemodynamically significant valvular heart disease such as mitral regurgitation, aortic stenosis, or aortic regurgitation or heart failure (New York Heart Association [NYHA] Class III-IV) of any etiology
- •Significant pulmonary insufficiency, including chronic obstructive pulmonary disease
- •Has homicidal ideation or intent, per the investigator's clinical judgment; or has suicidal ideation with some intent to act within 1 month prior to Day 1, per the investigator's clinical judgment; or based on the Columbia-suicide severity rating scale (C-SSRS) performed at Week 32 visit of Study 54135419TRD3013, corresponding to a response of "Yes" on Item 4 (active suicidal ideation with some intent to act, without specific plan) or Item 5 (active suicidal ideation with specific plan and intent) for suicidal ideation
- •Pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 90 days after the last dose of study intervention
研究组 & 干预措施
Esketamine
Participants who were randomly assigned to the esketamine arm in Study 54135419TRD3013 (NCT04338321), had esketamine nasal spray administered through Week 30 (every 2 weeks dosing) or Week 31 (once weekly dosing), completed the maintenance phase at Week 32 will continue to receive esketamine nasal spray once weekly or every 2 weeks along with serotonin-norepinephrine reuptake inhibitor/selective serotonin reuptake inhibitor (SSRI/SNRI) in this long-term extension (LTE) study. The duration of the study participation is 2 years or when esketamine is commercially available.
干预措施: Esketamine (Drug)
Esketamine
Participants who were randomly assigned to the esketamine arm in Study 54135419TRD3013 (NCT04338321), had esketamine nasal spray administered through Week 30 (every 2 weeks dosing) or Week 31 (once weekly dosing), completed the maintenance phase at Week 32 will continue to receive esketamine nasal spray once weekly or every 2 weeks along with serotonin-norepinephrine reuptake inhibitor/selective serotonin reuptake inhibitor (SSRI/SNRI) in this long-term extension (LTE) study. The duration of the study participation is 2 years or when esketamine is commercially available.
干预措施: SSRI/SNRI (Drug)
结局指标
主要结局
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
时间窗: From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)
Percentage of participants with TEAEs were reported. An AE was any untoward medical occurrence in a clinical study participant 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.
Incidence Rate of Treatment-emergent Adverse Events (TEAEs)
时间窗: From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)
Incidence rate of TEAEs were reported. AE Incidence rate was defined as incidence rate per 100 patient-months = (number of participants 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 participant 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.
Percentage of Participants With Treatment-emergent Serious Adverse Events (TESAEs)
时间窗: From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)
Percentage of participants with TESAEs were reported. An AE was any untoward medical occurrence in a clinical study participant 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.
Incidence Rate of Treatment-emergent Serious Adverse Events (TESAEs)
时间窗: From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)
Incidence rate of with TESAEs were reported. AE Incidence rate was defined as incidence rate per 100 patient-months = (number of participants 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 participant 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.
Percentage of of Participants With TEAEs Leading to Death
时间窗: From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)
Percentage of participants with TEAEs leading to death were reported. An AE was any untoward medical occurrence in a clinical study participant 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.
Incidence Rate of TEAEs Leading to Death
时间窗: From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)
Incidence rate of TEAEs leading to death were reported. AE Incidence rate was defined as incidence rate per 100 patient-months = (number of participants 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 participant 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.
Percentage of Participants With Treatment-emergent AEs of Special Interest (AESIs)
时间窗: From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)
Percentage of participants with TEAEs of special interest were reported. An AE was any untoward medical occurrence in a clinical study participant 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.
Incidence Rate of Treatment-emergent AEs of Special Interest (AESIs)
时间窗: From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)
AE Incidence rate: incidence rate per 100 patient-months=(number of participants 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 participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with intervention. SAE: AE resulting in any 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 intervention administration 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 grouped as categories sedation, dissociation, suicidality, suggestive of abuse potential, cystitis and hepatic impairment.
Number of Participants With Suicidal Ideation and Behavior in Study 54135419TRD4010 as Assessed by Columbia-suicide Severity Rating Scale (C-SSRS) Score
时间窗: Baseline (Day 1 of Study 54135419TRD3013) up to Week 104 of study 54135419TRD4010 (up to Week 136)
Number of participants with suicidal ideation and behavior in study 54135419TRD4010 as assessed by C-SSRS score were reported. C-SSRS score: 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. Total score from 10 categories was summarized into 3 categories: No suicidal ideation or behavior (0), Suicidal ideation (1 to 5), Suicidal behavior (6 to 10). Total score ranged from 0 to 10. Higher scores indicated more severe suicidal ideation and behavior.
次要结局
- Percentage of Participants With No Relapse and Without Discontinuation Until the End of the Prospective Observation Period at Week 104(Baseline (Day 1 of Study 54135419TRD3013) up to Week 104 of study 54135419TRD4010 (up to Week 136))
- Change From Baseline of Study 54135419TRD3013 in Clinician-rated Montgomery-Asberg Depression Rating Scale (MADRS) Total Score(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)
- Change From Baseline of Study 54135419TRD3013 in Clinician-rated Montgomery-Asberg Depression Rating Scale (MADRS) Score Individual Items(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)
- Change From Baseline of Study 54135419TRD3013 in Clinical Global Impression -Severity (CGI-S) Scale Score(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)
- Change From Baseline of Study 54135419TRD3013 in Patient Health Questionnaire (PHQ) 9-item Total Score(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)
- Change From Baseline of Study 54135419TRD3013 in European Quality of Life (EuroQol) 5 Dimension 5-Level (EQ-5D-5L): Health Status Index(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)
- Change From Baseline of Study 54135419TRD3013 in European Quality of Life (EuroQol) 5 Dimension 5-Level (EQ-5D-5L): Visual Analogue Scale (VAS)(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)