Title
Study to Evaluate SAGE-547 Injection as Adjunctive Therapy for the Treatment of Super-Refractory Status Epilepticus
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
Phase
Phase 1/Phase 2Lead Sponsor
Sage TherapeuticsStudy Type
InterventionalStatus
Completed Results PostedIndication/Condition
Super-refractory Status EpilepticusIntervention/Treatment
brexanolone ...Study Participants
25The purpose of this study is to evaluate the safety and tolerability of SAGE-547 in participants in super-refractory status epilepticus (SRSE).
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.
Solution for injection for IV infusion
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.
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.
Inclusion Criteria: 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). Exclusion Criteria: 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.
| Event Type | Organ System | Event Term | SAGE-547 Standard Dose | SAGE-547 High Dose |
|---|
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
