Super-refractory Status Epilepticus Clinical Trial
— SRSEOfficial title:
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
| Verified date | April 2022 |
| Source | Sage Therapeutics |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
The purpose of this study is to evaluate the safety and tolerability of SAGE-547 in participants in super-refractory status epilepticus (SRSE).
| Status | Completed |
| Enrollment | 25 |
| Est. completion date | May 3, 2015 |
| Est. primary completion date | May 3, 2015 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 2 Years and older |
| Eligibility | 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. |
| Country | Name | City | State |
|---|---|---|---|
| United States | Sage Investigational Site | Ann Arbor | Michigan |
| United States | Sage Investigational Site | Birmingham | Alabama |
| United States | Sage Investigational Site | Boston | Massachusetts |
| United States | Sage Investigational Site | Boston | Massachusetts |
| United States | Sage Investigational Site | Chicago | Illinois |
| United States | Sage Investigational Site | Dallas | Texas |
| United States | Sage Investigational Site | Detroit | Michigan |
| United States | Sage Investigational Site | Durham | North Carolina |
| United States | Sage Investigational Site | Nashville | Tennessee |
| United States | Sage Investigational Site | New Orleans | Louisiana |
| United States | Sage Investigational Site | New York | New York |
| United States | Sage Investigational Site | Philadelphia | Pennsylvania |
| United States | Sage Investigational Site | Rochester | New York |
| United States | Sage Investigational Site | Sarasota | Florida |
| United States | Sage Investigational Site | Temple | Texas |
| United States | Sage Investigational Site | Wichita | Kansas |
| United States | Sage Investigational Site | Winston-Salem | North Carolina |
| Lead Sponsor | Collaborator |
|---|---|
| Sage Therapeutics |
United States,
Rosenthal ES, Claassen J, Wainwright MS, Husain AM, Vaitkevicius H, Raines S, Hoffmann E, Colquhoun H, Doherty JJ, Kanes SJ. Brexanolone as adjunctive therapy in super-refractory status epilepticus. Ann Neurol. 2017 Sep;82(3):342-352. doi: 10.1002/ana.25008. Epub 2017 Sep 11. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 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. | Up to Day 29 | |
| Primary | Change From Baseline (CFB) in National Institutes of Health Stroke Scale (NIH-SS) Total Score | 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. | 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 | |
| Primary | Change From Baseline in Vital Sign Parameter: Body Weight | 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. | 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 | |
| Primary | Change From Baseline in Vital Sign Parameter: Heart Rate | 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. | 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 | |
| Primary | Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP | 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. | 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 | |
| Primary | Change From Baseline in Vital Sign Parameter: Respiratory Rate | 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. | 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 | |
| Primary | Change From Baseline in Vital Sign Parameter: Body Temperature | 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. | 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 | |
| Primary | Change From Baseline in Vital Sign Parameter: Oxygen Saturation | 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. | 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 | |
| Primary | Change From Baseline in Serum Chemistry Parameter: Alanine Aminotransferase Levels | 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. | 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 | |
| Primary | Change From Baseline in Serum Chemistry Parameter: Albumin Levels | 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. | 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 | |
| Primary | Change From Baseline in Serum Chemistry Parameter: Aspartate Aminotransferase Levels | 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. | 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 | |
| Primary | Change From Baseline in Serum Chemistry Parameter: Bicarbonate Levels | 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. | 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 | |
| Primary | Change From Baseline in Serum Chemistry Parameter: Bilirubin Levels | 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. | 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 | |
| Primary | Change From Baseline in Serum Chemistry Parameter: Blood Urea Nitrogen Levels | 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. | 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 | |
| Primary | Change From Baseline in Serum Chemistry Parameter: Calcium Levels | 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. | 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 | |
| Primary | Change From Baseline in Serum Chemistry Parameter: Chloride Levels | 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. | 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 | |
| Primary | Change From Baseline in Serum Chemistry Parameter: Creatine Kinase Levels | 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. | 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 | |
| Primary | Change From Baseline in Serum Chemistry Parameter: Creatinine Levels | 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. | 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 | |
| Primary | Change From Baseline in Serum Chemistry Parameter: Glucose Levels | 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. | 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 | |
| Primary | Change From Baseline in Serum Chemistry Parameter: Lipase Levels | 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. | 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 | |
| Primary | Change From Baseline in Serum Chemistry Parameter: Magnesium Levels | 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. | 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 | |
| Primary | Change From Baseline in Serum Chemistry Parameter: Potassium Levels | 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. | 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 | |
| Primary | Change From Baseline in Serum Chemistry Parameter: Protein Levels | 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. | 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 | |
| Primary | Change From Baseline in Serum Chemistry Parameter: Sodium Levels | 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. | 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 | |
| Primary | Change From Baseline in Hematology Parameter: Basophil Levels | 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. | 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 | |
| Primary | Change From Baseline in Hematology Parameter: Basophils to Leukocytes Ratio Reported in Percentage of Cells | 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. | 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 | |
| Primary | Change From Baseline in Hematology Parameter: Eosinophil Levels | 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. | 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 | |
| Primary | Change From Baseline in Hematology Parameter: Eosinophils to Leukocytes Ratio Reported in Percentage of Cells | 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. | 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 | |
| Primary | Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin Concentration Levels | 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. | 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 | |
| Primary | Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin Levels | 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. | 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 | |
| Primary | Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume Levels | 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. | 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 | |
| Primary | Change From Baseline in Hematology Parameter: Erythrocyte Levels | 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. | 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 | |
| Primary | Change From Baseline in Hematology Parameter: Hematocrit Levels | 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. | 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 | |
| Primary | Change From Baseline in Hematology Parameter: Hemoglobin Levels | 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. | 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 | |
| Primary | Change From Baseline in Hematology Parameter: Leukocyte Levels | 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. | 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 | |
| Primary | Change From Baseline in Hematology Parameter: Lymphocyte Levels | 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. | 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 | |
| Primary | Change From Baseline in Hematology Parameter: Lymphocytes to Leukocytes Ratio Reported in Percentage of Cells | 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. | 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 | |
| Primary | Change From Baseline in Hematology Parameter: Monocyte Levels | 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. | 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 | |
| Primary | Change From Baseline in Hematology Parameter: Monocytes to Leukocytes Ratio Reported in Percentage of Cells | 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. | 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 | |
| Primary | Change From Baseline in Hematology Parameter: Neutrophil Levels | 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. | 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 | |
| Primary | Change From Baseline in Hematology Parameter: Neutrophils to Leukocytes Ratio Reported in Percentage of Cells | 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. | 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 | |
| Primary | Change From Baseline in Hematology Parameter: Platelet Levels | 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. | 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 | |
| Primary | Change From Baseline in Electrocardiogram (ECG) Parameter: Heart Rate | ECG measures included heart rate, PR interval, QT interval, QRS duration and QTc interval. CFB in heart rate is reported in this outcome measure. | 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 | |
| Primary | Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval | 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. | 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 | |
| Primary | Number of Participants With Prior Anti-epileptic Drugs (AEDs) and Pressors Usage | Prior AEDs and Pressors are those medications that ended before the initiation of SAGE-547 infusion. | Up to Day 29 | |
| Secondary | Number of Participants With Relapse - Re-Initiation of Third-Line Agent | Relapse of participants is defined as successfully weaning from a continuous IV third-line agent but subsequent requirement of re-initiation of a third-line agent following conclusion of SAGE-547 treatment. | Up to Day 29 | |
| Secondary | Number of Participants With Treatment Response (Treatment Responders) | A responder was defined as a participant for whom it was not required to re-initiate continuous IV third-line therapy for refractory seizure control during the administration of SAGE-547 at the maintenance dose (prior to SAGE-547 taper infusion). | Up to 96 hours | |
| Secondary | Duration of Response | Duration of response was defined as the time from the stop date/time of SAGE-547 maintenance to re-initiation of a third-line agent. If no re-initiation of a third-line agent was required, duration of response was not estimable and censored at Day 29 or death date, whichever occurred first. Kaplan-Meier method was used for the analysis. | Up to Day 29 | |
| Secondary | 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 | ||
| Secondary | 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 | ||
| Secondary | 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 | ||
| Secondary | 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 | ||
| Secondary | 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 | ||
| Secondary | Average Plasma Concentration (Cav) of SAGE-547 | Pre-dose (0 hours), 1, 2, 4, 8, 24, 48, 72 and 96 hours post-dose | ||
| Secondary | Plasma Clearance (CL) of SAGE-547 | Clearance is defined as the volume of plasma from which a substance is completely removed per unit time. | Pre-dose (0 hours), 1, 2, 4, 8, 24, 48, 72, 96, 104, 112, 120 and 144 hours post-dose | |
| Secondary | Change From Baseline in Modified Rankin Scale (mRS-9Q) Scores | The mRS-9Q is a commonly used scale to determine disability and functional dependence due to neurological insult such as a stroke. It is a shortened version consisting of 9 questions. The score was categorized on the scale of 0 to 5 (0 = No symptoms, 1 = No significant disability, able to carry out all usual activities, despite some symptoms, 2 = Slight disability, able to look after own affairs without assistance, but unable to carry out all previous activities, 3 = Moderate disability, requires some help, but able to walk unassisted, 4 = Moderately severe disability, unable to attend to own bodily needs without assistance or unable to walk unassisted, and 5 = Severe disability, requires constant nursing care and attention, bedridden). Higher scores indicated worsening of symptoms. | Baseline (Screening) to Infusion at 49-72 hour, 73-96 hour; Extended follow-up at Day 8, 15, 22 and 29 | |
| Secondary | Change From Baseline in Clinical Global Impression: Severity Scale (CGI-S) | The CGI-Severity (CGI-S) scale employs a 7-point Likert scale to assess the severity of participant's current illness state. Clinician responded to a question "Considering your total clinical experience with this particular population, how mentally ill is your patient at this time?" on the following scores: 1 = Normal, not at all ill, 2 = Borderline ill, 3 = Mildly ill, 4 = Moderately ill, 5 = Markedly ill, 6 = Severely ill, and 7 = Among the most extremely ill, where higher score = more affected. | Baseline (Screening), Extended follow-up at Days 8, 15, 22, and 29 | |
| Secondary | Clinical Global Impression: Improvement Scale (CGI-I) Scores | The CGI-I response was defined as having a score of 1 (very much improved) or 2 (much improved). CGI-I item employs a 7-point Likert scale to measure the overall improvement in the participant's condition post-treatment. The investigator rated the participant's total improvement whether or not it was due entirely to drug treatment. Response choices included: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse; where higher scores indicated worst outcomes. The CGI-I was only rated at post-treatment assessments. By definition, all CGI-I assessments were evaluated against baseline conditions. | 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 | |
| Secondary | Change From Baseline in Glasgow Coma Scale (GCS) Scores | The Glasgow Coma Scale is divided into three components which are scored separately: ocular response (assessment 1-4 points), motor response (assessment 1-6 points), verbal response (evaluation of 1-5 points). Scores for each component are added together to get the total score that will range between a minimum of 3 points (which corresponds to a participant who does not open his/her eyes and no motor response to stimulation or verbal response) and a maximum value of 15 points (corresponding to a participant with open eyes, obeying orders and maintaining a consistent language). It has been considered that the GCS score between 15 and 13 points corresponds to a slight alteration of consciousness, a score of 12-9 points with moderate impairment and 8 points or less with a serious deterioration in level of consciousness. | 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 | |
| Secondary | Change From Baseline in Richmond Agitation Sedation Scale (RASS) Score | The RASS was an assessment of agitation and sedation in hospitalized participants, using a 10 point scale (ranged from -5 to +4), where, -5 = Unarousable, -4 = Deep sedation, -3 = Moderate sedation, -2 = Light sedation, -1 = Drowsy, 0 = Alert and calm, +1 = Restless, +2 = Agitated, +3 = Very agitated and +4 = Combative. Lower scores signify higher levels of sedation and higher scores signify heightened agitation. Participant in a calm and alert state would score a 0. | 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 | |
| Secondary | Number of Participants Who Survived | Survival time was defined as duration of survival from screening up to Day 29. | Up to Day 29 |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT02477618 -
A Study With SAGE-547 for Super-Refractory Status Epilepticus
|
Phase 3 | |
| No longer available |
NCT02433314 -
An Open Label, Expanded Access Protocol With SAGE-547 for Super-Refractory Status Epilepticus
|
N/A |