An Open-Label Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of SAGE-547 Injection as Adjunctive Therapy for the Treatment of Super-Refractory Status Epilepticus
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Change From Baseline in Vital Sign Parameter: Body Temperature
研究概览
简要总结
The purpose of this study is to evaluate the safety and tolerability of SAGE-547 in participants in super-refractory status epilepticus (SRSE).
详细描述
This is an open-label study consisting of a screening period (1 day), 4-day treatment period (96 hours) followed by a 1-day dose taper period (24 hours), a 2-day acute follow-up period, and a 3 week extended follow-up period.
On Day 1 of treatment SRSE participants under seizure suppression or burst-suppression with a continuous intravenous (IV) anti-epileptic drug (AED) (third-line agent) were given a 1-hour IV loading infusion of SAGE-547 followed by a maintenance infusion. After 48 hours of SAGE-547 treatment, the continuous IV AED (third-line agent) was weaned while continuing SAGE-547 at the maintenance infusion for the remainder of the treatment period. After 96 hours (4 days) of therapy with SAGE-547, the dose was to be tapered and discontinued over 24 hours.
The participants would have routine continuous electroencephalogram (EEG) monitoring during the screening period, and continuing until 48 hours after SAGE-547 treatment had completed. Participants would then have follow-up examinations weekly for the next 3 weeks (Days 8, 15, 22, and 29), during which safety and functional assessments would be obtained. Apart from treatment with SAGE-547, all participants would receive the standard of care for adults in SRSE along with ongoing treatment for all underlying medical conditions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants 2 years of age and older.
- •Participants with an EEG-confirmed SRSE diagnosis under concomitant therapy with a continuous IV AED (third-line agent) for ≥ 24 hours. For this study, SRSE is defined by the following criteria and in accordance with those used at major epilepsy treatment centers:
- •Failure to respond to the administration of at least one first-line agent (e.g., benzodiazepine or other emergent initial AED treatment), according to institution standard of care, and
- •Failure to respond to at least one second-line agent (e.g., phenytoin, fosphenytoin, valproate, phenobarbital, levetiracetam or other urgent control AED) according to institution standard of care, and
- •Presence of one or more breakthrough seizures > 6 hours after initiation of the continuous IV AED/third-line agent (e.g., pentobarbital, midazolam, propofol).
排除标准
- •Participants with SRSE due to anoxic/hypoxic encephalopathy, children (participants aged less than 18 years) with an encephalopathy due to an underlying progressive neurological disorder.
- •Participants with clinically significant electrocardiogram abnormalities.
- •Participants with a significant medical or surgical condition that may compromise vital organ systems, or other conditions that would place the participants at increased risk such as dialysis or acute respiratory distress syndrome, severe cardiogenic or vasodilatory shock requiring 2 or more pressors, fulminant hepatic failure, etc.
- •Participants who are receiving a continuous IV AED (third-line agent) for seizure suppression or burst-suppression that would require greater than 24 hours to wean.
研究组 & 干预措施
SAGE-547 Standard Dose
Participants received SAGE-547 IV loading infusion of 286.6 micrograms per kilogram per hour (μg/kg/hr) for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.
干预措施: SAGE-547 (Drug)
SAGE-547 High Dose
Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
干预措施: SAGE-547 (Drug)
结局指标
主要结局
Change From Baseline in Vital Sign Parameter: Body Temperature
时间窗: Baseline (Screening) to infusion at 0-24 hours: Loading-predose and at 15,30,45 minutes;1,2,4,8 and 24 hour;25-48: 48 hour;49-72:72 hours;73-96: 96 hour;97-120:120 hours;Acute follow-up at 121-144,145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Vital signs included weight, heart rate, blood pressure (SBP and DBP), respiratory rate, temperature, oxygen saturation. CFB in body temperature is reported in this outcome measure.
Change From Baseline in Vital Sign Parameter: Body Weight
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Vital signs included weight, heart rate, blood pressure (systolic blood pressure (SBP) and diastolic blood pressure (DBP)), respiratory rate, temperature, oxygen saturation. CFB in body weight is reported in this outcome measure.
Change From Baseline (CFB) in National Institutes of Health Stroke Scale (NIH-SS) Total Score
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
The National Institutes of Health Stroke Scale (NIH-SS) was used to examine the physical and neurological state of the participants. The NIH-SS is a 15-item assessment with measures of level of consciousness, visual gaze and vision loss, facial palsy, motor ability, ataxia, sensory ability, aphasia, dysarthria, and inattention. The total NIHSS score range is from 0 (normal) to 42 (severe impairment), with higher values indicating greater level of neurological impairment.
Change From Baseline in Vital Sign Parameter: Heart Rate
时间窗: Baseline (Screening) to infusion at 0-24 hours: Loading-predose and at 15,30,45 minutes;1,2,4,8 and 24 hour;25-48: 48 hour;49-72:72 hours;73-96: 96 hour;97-120:120 hours;Acute follow-up at 121-144,145-168 hours; Extended Follow-up at Days 8, 15, 22 and 29
Vital signs included weight, heart rate, blood pressure (SBP and DBP), respiratory rate, temperature, oxygen saturation. CFB in heart rate is reported in this outcome measure.
Change From Baseline in Vital Sign Parameter: Oxygen Saturation
时间窗: Baseline (Screening) to infusion at 0-24 hours: Loading-predose and at 15,30,45 minutes;1,2,4,8 and 24 hour;25-48: 48 hour;49-72:72 hours;73-96: 96 hour;97-120:120 hours;Acute follow-up at 121-144,145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Vital signs included weight, heart rate, blood pressure (SBP and DBP), respiratory rate, temperature, oxygen saturation. Oxygen saturation is a measure of how much hemoglobin is currently bound to oxygen compared to how much hemoglobin remains unbound. CFB in oxygen saturation is reported in this outcome measure.
Change From Baseline in Hematology Parameter: Basophil Levels
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes mean corpuscular hemoglobin concentration, erythrocytes mean corpuscular hemoglobin, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets. CFB in basophil levels is reported in this outcome measure.
Change From Baseline in Serum Chemistry Parameter: Alanine Aminotransferase Levels
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Serum chemistry measures included alanine aminotransferase, albumin, aspartate aminotransferase, bicarbonate, bilirubin, blood urea nitrogen, calcium, chloride, creatine kinase, creatinine, glucose, lipase, magnesium, potassium, protein, sodium. CFB in alanine aminotransferase levels is reported in this outcome measure.
Change From Baseline in Serum Chemistry Parameter: Calcium Levels
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Serum chemistry measures included alanine aminotransferase, albumin, aspartate aminotransferase, bicarbonate, bilirubin, blood urea nitrogen, calcium, chloride, creatine kinase, creatinine, glucose, lipase, magnesium, potassium, protein, sodium. CFB in calcium levels is reported in this outcome measure.
Change From Baseline in Serum Chemistry Parameter: Creatinine Levels
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Serum chemistry measures included alanine aminotransferase, albumin, aspartate aminotransferase, bicarbonate, bilirubin, blood urea nitrogen, calcium, chloride, creatine kinase, creatinine, glucose, lipase, magnesium, potassium, protein, sodium. CFB in creatinine levels is reported in this outcome measure.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
时间窗: Up to Day 29
An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. TEAEs are defined as those that begin on or after initiation of the infusion of SAGE-547.
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP
时间窗: Baseline (Screening) to infusion at 0-24 hours:Loading-predose and at 15,30,45 minutes;1,2,4,8 and 24 hour;25-48: 48 hour;49-72: 72 hour;73-96: 96 hour;97-120:120 hour;Acute follow-up at 121-144,145-168 hours;Extended follow-up at Days 8,15,22 and 29
Vital signs included weight, heart rate, blood pressure (SBP and DBP), respiratory rate, temperature, oxygen saturation. CFB in SBP and DBP is reported in this outcome measure.
Change From Baseline in Vital Sign Parameter: Respiratory Rate
时间窗: Baseline (Screening) to infusion at 0-24 hours:Loading-predose and at 15,30,45 minutes;1,2,4,8 and 24 hour;25-48: 48 hour;49-72:72 hours;73-96: 96 hour;97-120:120 hours;Acute follow-up at 121-144,145-168 hours;Extended follow-up at Days 8, 15, 22 and 29
Vital signs included weight, heart rate, blood pressure (SBP and DBP), respiratory rate, temperature, oxygen saturation. CFB in respiratory rate is reported in this outcome measure.
Change From Baseline in Serum Chemistry Parameter: Aspartate Aminotransferase Levels
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Serum chemistry measures included alanine aminotransferase, albumin, aspartate aminotransferase, bicarbonate, bilirubin, blood urea nitrogen, calcium, chloride, creatine kinase, creatinine, glucose, lipase, magnesium, potassium, protein, sodium. CFB in aspartate aminotransferase levels is reported in this outcome measure.
Change From Baseline in Serum Chemistry Parameter: Chloride Levels
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Serum chemistry measures included alanine aminotransferase, albumin, aspartate aminotransferase, bicarbonate, bilirubin, blood urea nitrogen, calcium, chloride, creatine kinase, creatinine, glucose, lipase, magnesium, potassium, protein, sodium. CFB in chloride levels is reported in this outcome measure.
Change From Baseline in Serum Chemistry Parameter: Albumin Levels
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Serum chemistry measures included alanine aminotransferase, albumin, aspartate aminotransferase, bicarbonate, bilirubin, blood urea nitrogen, calcium, chloride, creatine kinase, creatinine, glucose, lipase, magnesium, potassium, protein, sodium. CFB in albumin levels is reported in this outcome measure.
Change From Baseline in Serum Chemistry Parameter: Bicarbonate Levels
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Serum chemistry measures included alanine aminotransferase, albumin, aspartate aminotransferase, bicarbonate, bilirubin, blood urea nitrogen, calcium, chloride, creatine kinase, creatinine, glucose, lipase, magnesium, potassium, protein, sodium. CFB in bicarbonate levels is reported in this outcome measure.
Change From Baseline in Serum Chemistry Parameter: Bilirubin Levels
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Serum chemistry measures included alanine aminotransferase, albumin, aspartate aminotransferase, bicarbonate, bilirubin, blood urea nitrogen, calcium, chloride, creatine kinase, creatinine, glucose, lipase, magnesium, potassium, protein, sodium. CFB in bilirubin levels is reported in this outcome measure.
Change From Baseline in Serum Chemistry Parameter: Blood Urea Nitrogen Levels
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Serum chemistry measures included alanine aminotransferase, albumin, aspartate aminotransferase, bicarbonate, bilirubin, blood urea nitrogen, calcium, chloride, creatine kinase, creatinine, glucose, lipase, magnesium, potassium, protein, sodium. CFB in blood urea nitrogen levels is reported in this outcome measure.
Change From Baseline in Serum Chemistry Parameter: Creatine Kinase Levels
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Serum chemistry measures included alanine aminotransferase, albumin, aspartate aminotransferase, bicarbonate, bilirubin, blood urea nitrogen, calcium, chloride, creatine kinase, creatinine, glucose, lipase, magnesium, potassium, protein, sodium. CFB in creatine kinase levels is reported in this outcome measure.
Change From Baseline in Hematology Parameter: Eosinophils to Leukocytes Ratio Reported in Percentage of Cells
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes mean corpuscular hemoglobin concentration, erythrocytes mean corpuscular hemoglobin, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets. CFB in eosinophils to leukocytes ratio is reported in terms of percentage of cells in this outcome measure.
Change From Baseline in Serum Chemistry Parameter: Protein Levels
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Serum chemistry measures included alanine aminotransferase, albumin, aspartate aminotransferase, bicarbonate, bilirubin, blood urea nitrogen, calcium, chloride, creatine kinase, creatinine, glucose, lipase, magnesium, potassium, protein, sodium. CFB in protein levels is reported in this outcome measure.
Change From Baseline in Serum Chemistry Parameter: Sodium Levels
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Serum chemistry measures included alanine aminotransferase, albumin, aspartate aminotransferase, bicarbonate, bilirubin, blood urea nitrogen, calcium, chloride, creatine kinase, creatinine, glucose, lipase, magnesium, potassium, protein, sodium. CFB in sodium levels is reported in this outcome measure.
Change From Baseline in Hematology Parameter: Hematocrit Levels
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes mean corpuscular hemoglobin concentration, erythrocytes mean corpuscular hemoglobin, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets. CFB in hematocrit levels is reported in this outcome measure.
Change From Baseline in Hematology Parameter: Neutrophils to Leukocytes Ratio Reported in Percentage of Cells
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes mean corpuscular hemoglobin concentration, erythrocytes mean corpuscular hemoglobin, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets. CFB in neutrophils to leukocytes ratio is reported in terms of percentage of cells in this outcome measure.
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
ECG measures included heart rate, PR interval, QT interval, QRS duration and QTc interval. CFB in PR interval, QT interval, QRS duration and QTc interval is reported in this outcome measure.
Change From Baseline in Serum Chemistry Parameter: Glucose Levels
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Serum chemistry measures included alanine aminotransferase, albumin, aspartate aminotransferase, bicarbonate, bilirubin, blood urea nitrogen, calcium, chloride, creatine kinase, creatinine, glucose, lipase, magnesium, potassium, protein, sodium. CFB in glucose levels is reported in this outcome measure.
Change From Baseline in Serum Chemistry Parameter: Lipase Levels
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Serum chemistry measures included alanine aminotransferase, albumin, aspartate aminotransferase, bicarbonate, bilirubin, blood urea nitrogen, calcium, chloride, creatine kinase, creatinine, glucose, lipase, magnesium, potassium, protein, sodium. CFB in lipase levels is reported in this outcome measure.
Change From Baseline in Hematology Parameter: Lymphocytes to Leukocytes Ratio Reported in Percentage of Cells
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes mean corpuscular hemoglobin concentration, erythrocytes mean corpuscular hemoglobin, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets. CFB in lymphocytes to leukocytes ratio is reported in terms of percentage of cells in this outcome measure.
Change From Baseline in Hematology Parameter: Monocyte Levels
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes mean corpuscular hemoglobin concentration, erythrocytes mean corpuscular hemoglobin, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets. CFB in monocyte levels is reported in this outcome measure.
Change From Baseline in Hematology Parameter: Neutrophil Levels
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes mean corpuscular hemoglobin concentration, erythrocytes mean corpuscular hemoglobin, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets. CFB in neutrophil levels is reported in this outcome measure.
Change From Baseline in Hematology Parameter: Platelet Levels
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes mean corpuscular hemoglobin concentration, erythrocytes mean corpuscular hemoglobin, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets. CFB in platelet levels is reported in this outcome measure.
Change From Baseline in Electrocardiogram (ECG) Parameter: Heart Rate
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
ECG measures included heart rate, PR interval, QT interval, QRS duration and QTc interval. CFB in heart rate is reported in this outcome measure.
Change From Baseline in Serum Chemistry Parameter: Magnesium Levels
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Serum chemistry measures included alanine aminotransferase, albumin, aspartate aminotransferase, bicarbonate, bilirubin, blood urea nitrogen, calcium, chloride, creatine kinase, creatinine, glucose, lipase, magnesium, potassium, protein, sodium. CFB in magnesium levels is reported in this outcome measure.
Change From Baseline in Serum Chemistry Parameter: Potassium Levels
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Serum chemistry measures included alanine aminotransferase, albumin, aspartate aminotransferase, bicarbonate, bilirubin, blood urea nitrogen, calcium, chloride, creatine kinase, creatinine, glucose, lipase, magnesium, potassium, protein, sodium. CFB in potassium levels is reported in this outcome measure.
Change From Baseline in Hematology Parameter: Basophils to Leukocytes Ratio Reported in Percentage of Cells
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes mean corpuscular hemoglobin concentration, erythrocytes mean corpuscular hemoglobin, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets. CFB in basophils to leukocytes ratio is reported in terms of percentage of cells in this outcome measure.
Change From Baseline in Hematology Parameter: Eosinophil Levels
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes mean corpuscular hemoglobin concentration, erythrocytes mean corpuscular hemoglobin, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets. CFB in eosinophils levels is reported in this outcome measure.
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume Levels
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes mean corpuscular hemoglobin concentration, erythrocytes mean corpuscular hemoglobin, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets. CFB in erythrocytes mean corpuscular volume levels is reported in this outcome measure.
Change From Baseline in Hematology Parameter: Leukocyte Levels
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes mean corpuscular hemoglobin concentration, erythrocytes mean corpuscular hemoglobin, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets. CFB in leukocyte levels is reported in this outcome measure.
Change From Baseline in Hematology Parameter: Lymphocyte Levels
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes mean corpuscular hemoglobin concentration, erythrocytes mean corpuscular hemoglobin, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets. CFB in lymphocyte levels is reported in this outcome measure.
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin Concentration Levels
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes mean corpuscular hemoglobin concentration, erythrocytes mean corpuscular hemoglobin, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets. CFB in erythrocytes mean corpuscular hemoglobin concentration levels is reported in this outcome measure.
Change From Baseline in Hematology Parameter: Hemoglobin Levels
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes mean corpuscular hemoglobin concentration, erythrocytes mean corpuscular hemoglobin, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets. CFB in hemoglobin levels is reported in this outcome measure.
Number of Participants With Prior Anti-epileptic Drugs (AEDs) and Pressors Usage
时间窗: Up to Day 29
Prior AEDs and Pressors are those medications that ended before the initiation of SAGE-547 infusion.
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin Levels
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes mean corpuscular hemoglobin concentration, erythrocytes mean corpuscular hemoglobin, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets. CFB in erythrocytes mean corpuscular hemoglobin levels is reported in this outcome measure.
Change From Baseline in Hematology Parameter: Erythrocyte Levels
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes mean corpuscular hemoglobin concentration, erythrocytes mean corpuscular hemoglobin, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets. CFB in erythrocyte levels is reported in this outcome measure.
Change From Baseline in Hematology Parameter: Monocytes to Leukocytes Ratio Reported in Percentage of Cells
时间窗: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29
Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes mean corpuscular hemoglobin concentration, erythrocytes mean corpuscular hemoglobin, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets. CFB in monocytes to leukocytes ratio is reported in terms of percentage of cells in this outcome measure.
次要结局
- Number of Participants Who Survived(Up to Day 29)
- Number of Participants With Relapse - Re-Initiation of Third-Line Agent(Up to Day 29)
- Maximum Plasma Concentration (Cmax) of SAGE-547(Pre-dose (0 hours), 1, 2, 4, 8, 24, 48, 72, 96, 104, 112, 120 and 144 hours post-dose)
- Plasma Clearance (CL) of SAGE-547(Pre-dose (0 hours), 1, 2, 4, 8, 24, 48, 72, 96, 104, 112, 120 and 144 hours post-dose)
- Number of Participants With Treatment Response (Treatment Responders)(Up to 96 hours)
- Change From Baseline in Richmond Agitation Sedation Scale (RASS) Score(Baseline (Screening) to Infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29)
- Time to Attain Maximum Observed Plasma Concentration (Tmax) of SAGE-547(Pre-dose (0 hours), 1, 2, 4, 8, 24, 48, 72, 96, 104, 112, 120 and 144 hours post-dose)
- Area Under the Plasma SAGE-547 Concentration-Time Curve in a 24 Hour Period (AUC24)(Pre-dose (0 hours), 1, 2, 4, 8 and 24 hours post-dose)
- Area Under the Plasma SAGE-547 Concentration-Time Curve (AUC1-96)(Pre-dose (0 hours), 1, 2, 4, 8, 24, 48, 72 and 96 hours post-dose)
- Average Plasma Concentration (Cav) of SAGE-547(Pre-dose (0 hours), 1, 2, 4, 8, 24, 48, 72 and 96 hours post-dose)
- Change From Baseline in Clinical Global Impression: Severity Scale (CGI-S)(Baseline (Screening), Extended follow-up at Days 8, 15, 22, and 29)
- Change From Baseline in Glasgow Coma Scale (GCS) Scores(Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29)
- Duration of Response(Up to Day 29)
- Areas Under the Plasma SAGE-547 Concentration Time Curves From the Start of the Infusion Until the Time to the Last Sample (AUClast)(Pre-dose (0 hours), 1, 2, 4, 8, 24, 48, 72, 96, 104, 112, 120 and 144 hours post-dose)
- Change From Baseline in Modified Rankin Scale (mRS-9Q) Scores(Baseline (Screening) to Infusion at 49-72 hour, 73-96 hour; Extended follow-up at Day 8, 15, 22 and 29)
- Clinical Global Impression: Improvement Scale (CGI-I) Scores(Infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29)