Evaluate SAGE-547 in Participants With Essential Tremor

NCT02277106 | Completed Phase 2 Results

• 1 other identifier: 547-ETD-201
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

Brief Summary

Stage 1 is a double-blind, proof-of-concept study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of SAGE-547 Injection in male and female participants with essential tremor in the upper limb. Stage 2 is an open-label arm designed to evaluate the safety, tolerability, PK, and effectiveness of SAGE-547 Injection at a higher dose than in Stage 1. Participants who completed Stage 1 were invited to participate in Stage 2.

Conditions

Essential Tremor

Outcome Measures

Primary Outcomes (98)

• Stage 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  An adverse event (AE) is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A TEAE was defined as an AE with start date/time after the start of initial infusion in each stage. An SAE is defined as an AE or suspected adverse reaction, which in the view of either the Investigator or Sponsor, results in any of the following outcomes: death; is life-threatening; inpatient hospitalization or prolongation of existing hospitalization; a persistent or significant disability or incapacity; congenital anomaly or birth defect or other medically important condition.

  Stage 1: Up to 30 days after last infusion (up to Day 40)

• Stage 2: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A TEAE was defined as an AE with start date/time after the start of initial infusion in each stage. An SAE is defined as an AE or suspected adverse reaction, which in the view of either the Investigator or Sponsor, results in any of the following outcomes: death; is life-threatening; inpatient hospitalization or prolongation of existing hospitalization; a persistent or significant disability or incapacity; congenital anomaly or birth defect or other medically important condition.

  Stage 2: Up to 30 days after last infusion (up to Day 31)

• Stage 1: Percentage of Participants With a Response of 'Yes' to Any Columbia Suicide Severity Rating Scale (C-SSRS) Suicidal Ideation or Suicidal Behavior Item at Any Visit

  The C-SSRS scale consisted of baseline evaluation that assessed lifetime experience of participants with suicidal ideation (SI) and suicidal behavior (SB) and postbaseline evaluation that focused on suicidality since last study visit. C-SSRS included "yes" or "no"' responses for assessment of suicidal ideation and behavior as well as numeric ratings for severity of ideation, if present \[from 1 (minor physical damage) to 5 (death), with 5 being most severe\]. C-SSRS SI items involved (a) wish to be dead, (b) non-specific active suicidal thoughts, (c) active SI with any methods (not plan) without intent to act, (d) active SI with some intent to act, without specific plan and (e) active SI with specific plan and intent. C-SSRS SB items involved (a) actual attempt, (b) engaged in non-suicidal self-injurious behavior, (c) interrupted attempt, (d) aborted attempt, (e) preparatory acts or behavior, (f) suicidal behavior. Only categories with data are reported.

  Stage 1: Pre-infusion on Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2)

• Stage 2: Percentage of Participants With a Response of 'Yes' to Any Columbia Suicide Severity Rating Scale (C-SSRS) Suicidal Ideation or Suicidal Behavior Item at Any Visit

  The C-SSRS scale consisted of baseline evaluation that assessed lifetime experience of participants with SI and SB and postbaseline evaluation that focused on suicidality since last study visit. C-SSRS included "yes" or "no"' responses for assessment of suicidal ideation and behavior as well as numeric ratings for severity of ideation, if present \[from 1 (minor physical damage) to 5 (death), with 5 being most severe\]. C-SSRS SI items involved (a) wish to be dead, (b) non-specific active suicidal thoughts, (c) active SI with any methods (not plan) without intent to act, (d) active SI with some intent to act, without specific plan and (e) active SI with specific plan and intent. C-SSRS SB items involved (a) actual attempt, (b) engaged in non-suicidal self-injurious behavior, (c) interrupted attempt, (d) aborted attempt, (e) preparatory acts or behavior, (f) suicidal behavior.

  Stage 2 Day 1: Pre-infusion and 10 hours and 7-day follow-up post-infusion

• Stage 1: Change From Baseline (CFB) in Vital Signs Parameter - Supine Systolic Blood Pressure

  Vital signs included supine systolic blood pressure, supine diastolic blood pressure, supine heart rate, standing systolic blood pressure, standing diastolic blood pressure, standing heart rate, temperature, and respiratory rate. CFB in supine systolic blood pressure is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 4, 8, 12 hours during infusion and 12-hour follow-up post-infusion

• Stage 2: Change From Baseline in Vital Signs Parameter - Supine Systolic Blood Pressure

  Vital signs included supine systolic blood pressure, supine diastolic blood pressure, supine heart rate, standing systolic blood pressure, standing diastolic blood pressure, standing heart rate, temperature, and respiratory rate. CFB in supine systolic blood pressure is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Stage 2 Day 1: Pre-infusion (Baseline) and 2, 4, 6, 8, 10, 12, 14 and 24 hours post-infusion

• Stage 1: Change From Baseline in Vital Signs Parameter - Supine Diastolic Blood Pressure

  Vital signs included supine systolic blood pressure, supine diastolic blood pressure, supine heart rate, standing systolic blood pressure, standing diastolic blood pressure, standing heart rate, temperature, and respiratory rate. CFB in supine diastolic blood pressure is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 4, 8, 12 hours during infusion and 12-hour follow-up post-infusion

• Stage 2: Change From Baseline in Vital Signs Parameter - Supine Diastolic Blood Pressure

  Vital signs included supine systolic blood pressure, supine diastolic blood pressure, supine heart rate, standing systolic blood pressure, standing diastolic blood pressure, standing heart rate, temperature, and respiratory rate. CFB in supine diastolic blood pressure is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Stage 2 Day 1: Pre-infusion (Baseline) and 2, 4, 6, 8, 10, 12, 14 and 24 hours post-infusion

• Stage 1: Change From Baseline in Vital Signs Parameter - Supine Heart Rate

  Vital signs included supine systolic blood pressure, supine diastolic blood pressure, supine heart rate, standing systolic blood pressure, standing diastolic blood pressure, standing heart rate, temperature, and respiratory rate. CFB in supine heart rate is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 4, 8, 12 hours during infusion and 12-hour follow-up post-infusion

• Stage 2: Change From Baseline in Vital Signs Parameter - Supine Heart Rate

  Vital signs included supine systolic blood pressure, supine diastolic blood pressure, supine heart rate, standing systolic blood pressure, standing diastolic blood pressure, standing heart rate, temperature, and respiratory rate. CFB in supine heart rate is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Stage 2 Day 1: Pre-infusion (Baseline) and 2, 4, 6, 8, 10, 12, 14 and 24 hours post-infusion

• Stage 1: Change From Baseline in Vital Signs Parameter - Standing Systolic Blood Pressure

  Vital signs included supine systolic blood pressure, supine diastolic blood pressure, supine heart rate, standing systolic blood pressure, standing diastolic blood pressure, standing heart rate, temperature, and respiratory rate. CFB in standing systolic blood pressure is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 4, 8, 12 hours during infusion and 12-hour follow-up post-infusion

• Stage 2: Change From Baseline in Vital Signs Parameter - Standing Systolic Blood Pressure

  Vital signs included supine systolic blood pressure, supine diastolic blood pressure, supine heart rate, standing systolic blood pressure, standing diastolic blood pressure, standing heart rate, temperature, and respiratory rate. CFB in standing systolic blood pressure is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Stage 2 Day 1: Pre-infusion (Baseline) and 2, 4, 6, 8, 10, 12, 14 and 24 hours post-infusion

• Stage 1: Change From Baseline in Vital Signs Parameter - Standing Diastolic Blood Pressure

  Vital signs included supine systolic blood pressure, supine diastolic blood pressure, supine heart rate, standing systolic blood pressure, standing diastolic blood pressure, standing heart rate, temperature, and respiratory rate. CFB in standing diastolic blood pressure is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 4, 8, 12 hours during infusion and 12-hour follow-up post-infusion

• Stage 2: Change From Baseline in Vital Signs Parameter - Standing Diastolic Blood Pressure

  Vital signs included supine systolic blood pressure, supine diastolic blood pressure, supine heart rate, standing systolic blood pressure, standing diastolic blood pressure, standing heart rate, temperature, and respiratory rate. CFB in standing diastolic blood pressure is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Stage 2 Day 1: Pre-infusion (Baseline) and 2, 4, 6, 8, 10, 12, 14 and 24 hours post-infusion

• Stage 1: Change From Baseline in Vital Signs Parameter - Standing Heart Rate

  Vital signs included supine systolic blood pressure, supine diastolic blood pressure, supine heart rate, standing systolic blood pressure, standing diastolic blood pressure, standing heart rate, temperature, and respiratory rate. CFB in standing heart rate is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 4, 8, 12 hours during infusion and 12-hour follow-up post-infusion

• Stage 2: Change From Baseline in Vital Signs Parameter - Standing Heart Rate

  Vital signs included supine systolic blood pressure, supine diastolic blood pressure, supine heart rate, standing systolic blood pressure, standing diastolic blood pressure, standing heart rate, temperature, and respiratory rate. CFB in standing heart rate is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Stage 2 Day 1: Pre-infusion (Baseline) and 2, 4, 6, 8, 10, 12, 14 and 24 hours post-infusion

• Stage 1: Change From Baseline in Vital Signs Parameter - Temperature

  Vital signs included supine systolic blood pressure, supine diastolic blood pressure, supine heart rate, standing systolic blood pressure, standing diastolic blood pressure, standing heart rate, temperature, and respiratory rate. CFB in temperature is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 4, 8, 12 hours during infusion and 12-hour follow-up post-infusion

• Stage 2: Change From Baseline in Vital Signs Parameter - Temperature

  Vital signs included supine systolic blood pressure, supine diastolic blood pressure, supine heart rate, standing systolic blood pressure, standing diastolic blood pressure, standing heart rate, temperature, and respiratory rate. CFB in temperature is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Stage 2 Day 1: Pre-infusion (Baseline) and 2, 4, 6, 8, 10, 12, 14 and 24 hours post-infusion

• Stage 1: Change From Baseline in Vital Signs Parameter - Respiratory Rate

  Vital signs included supine systolic blood pressure, supine diastolic blood pressure, supine heart rate, standing systolic blood pressure, standing diastolic blood pressure, standing heart rate, temperature, and respiratory rate. CFB in respiratory rate is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 4, 8, 12 hours during infusion and 12-hour follow-up post-infusion

• Stage 2: Change From Baseline in Vital Signs Parameter - Respiratory Rate

  Vital signs included supine systolic blood pressure, supine diastolic blood pressure, supine heart rate, standing systolic blood pressure, standing diastolic blood pressure, standing heart rate, temperature, and respiratory rate. CFB in respiratory rate is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Stage 2 Day 1: Pre-infusion (Baseline) and 2, 4, 6, 8, 10, 12, 14 and 24 hours post-infusion

• Stage 1: Change From Baseline in Serum Chemistry Parameter - Alanine Aminotransferase Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in alanine aminotransferase levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

• Stage 2: Absolute Values of Serum Chemistry Parameter - Alanine Aminotransferase Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for alanine aminotransferase levels are reported in this outcome measure.

  Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

• Stage 1: Change From Baseline in Serum Chemistry Parameter - Aspartate Aminotransferase Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in aspartate aminotransferase levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

• Stage 2: Absolute Values of Serum Chemistry Parameter - Aspartate Aminotransferase Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for aspartate aminotransferase levels are reported in this outcome measure.

  Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

• Stage 1: Change From Baseline in Serum Chemistry Parameter - Gamma Glutamyl Transferase Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in gamma glutamyl transferase levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

• Stage 2: Absolute Values of Serum Chemistry Parameter - Gamma Glutamyl Transferase Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for gamma glutamyl transferase levels are reported in this outcome measure.

  Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

• Stage 1: Change From Baseline in Serum Chemistry Parameter - Sodium Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in sodium levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

• Stage 2: Absolute Values of Serum Chemistry Parameter - Sodium Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for sodium levels are reported in this outcome measure.

  Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

• Stage 1: Change From Baseline in Serum Chemistry Parameter - Potassium Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in potassium levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

• Stage 2: Absolute Values of Serum Chemistry Parameter - Potassium Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for potassium levels are reported in this outcome measure.

  Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

• Stage 1: Change From Baseline in Serum Chemistry Parameter - Calcium Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in calcium levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

• Stage 2: Absolute Values of Serum Chemistry Parameter - Calcium Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for calcium levels are reported in this outcome measure.

  Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

• Stage 1: Change From Baseline in Serum Chemistry Parameter - Chloride Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in chloride levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

• Stage 2: Absolute Values of Serum Chemistry Parameter - Chloride Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for chloride levels are reported in this outcome measure.

  Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

• Stage 1: Change From Baseline in Serum Chemistry Parameter - Bicarbonate Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in bicarbonate levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

• Stage 2: Absolute Values of Serum Chemistry Parameter - Bicarbonate Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for bicarbonate levels are reported in this outcome measure.

  Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

• Stage 1: Change From Baseline in Serum Chemistry Parameter - Protein Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in protein levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

• Stage 2: Absolute Values of Serum Chemistry Parameter - Protein Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for protein levels are reported in this outcome measure.

  Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

• Stage 1: Change From Baseline in Serum Chemistry Parameter - Glucose Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in glucose levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

• Stage 2: Absolute Values of Serum Chemistry Parameter - Glucose Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for glucose levels are reported in this outcome measure.

  Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

• Stage 1: Change From Baseline in Serum Chemistry Parameter - Lactate Dehydrogenase Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in lactate dehydrogenase levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

• Stage 2: Absolute Values of Serum Chemistry Parameter - Lactate Dehydrogenase Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for lactate dehydrogenase levels are reported in this outcome measure.

  Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

• Stage 1: Change From Baseline in Serum Chemistry Parameter - Cholesterol Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in cholesterol levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

• Stage 2: Absolute Values of Serum Chemistry Parameter - Cholesterol Level

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for cholesterol levels are reported in this outcome measure.

  Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

• Stage 1: Change From Baseline in Serum Chemistry Parameter - Triglyceride Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in triglyceride levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

• Stage 2: Absolute Values of Serum Chemistry Parameter - Triglyceride Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for triglyceride levels are reported in this outcome measure.

  Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

• Stage 1: Change From Baseline in Serum Chemistry Parameter - Albumin Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in albumin levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

• Stage 2: Absolute Values of Serum Chemistry Parameter - Albumin Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for albumin levels are reported in this outcome measure.

  Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

• Stage 1: Change From Baseline in Serum Chemistry Parameter - Bilirubin Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in bilirubin levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

• Stage 2: Absolute Values of Serum Chemistry Parameter - Bilirubin Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for bilirubin levels are reported in this outcome measure.

  Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

• Stage 1: Change From Baseline in Serum Chemistry Parameter - Creatinine Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in creatinine levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

• Stage 2: Absolute Values of Serum Chemistry Parameter - Creatinine Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for creatinine levels are reported in this outcome measure.

  Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

• Stage 1: Change From Baseline in Serum Chemistry Parameter - Blood Urea Nitrogen Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in blood urea nitrogen levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

• Stage 2: Absolute Values of Serum Chemistry Parameter - Blood Urea Nitrogen Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for blood urea nitrogen levels are reported in this outcome measure.

  Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

• Stage 1: Change From Baseline in Serum Chemistry Parameter - Alkaline Phosphatase Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in alkaline phosphatase levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

• Stage 2: Absolute Values of Serum Chemistry Parameter - Alkaline Phosphatase Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for alkaline phosphatase levels are reported in this outcome measure.

  Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

• Stage 1: Change From Baseline in Serum Chemistry Parameter - Creatine Kinase Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in creatinine kinase levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

• Stage 2: Absolute Values of Serum Chemistry Parameter - Creatine Kinase Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for creatinine kinase levels are reported in this outcome measure.

  Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

• Stage 1: Change From Baseline in Serum Chemistry Parameter - Phosphate Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in phosphate levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

• Stage 2: Absolute Values of Serum Chemistry Parameter - Phosphate Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for phosphate levels are reported in this outcome measure.

  Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

• Stage 1: Change From Baseline in Serum Chemistry Parameter - Urate Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in urate levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

• Stage 2: Absolute Values of Serum Chemistry Parameter - Urate Levels

  Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for urate levels are reported in this outcome measure.

  Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

• Stage 1: Change From Baseline in Hematology Parameter - Hemoglobin Levels

  Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. CFB in hemoglobin levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

• Stage 2: Absolute Values of Hematology Parameter - Hemoglobin Levels

  Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. Absolute values for hemoglobin levels are reported in this outcome measure.

  Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

• Stage 1: Change From Baseline in Hematology Parameter - Hematocrit Levels

  Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. CFB in hematocrit levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

• Stage 2: Absolute Values of Hematology Parameter - Hematocrit Levels

  Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. Absolute values for hematocrit levels are reported in this outcome measure.

  Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

• Stage 1: Change From Baseline in Hematology Parameter - Platelet Levels

  Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. CFB in platelet levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

• Stage 2: Absolute Values of Hematology Parameter - Platelet Levels

  Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. Absolute values for platelet levels are reported in this outcome measure.

  Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

• Stage 1: Change From Baseline in Hematology Parameter - Erythrocyte Levels

  Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. CFB in erythrocyte levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

• Stage 2: Absolute Values of Hematology Parameter - Erythrocyte Levels

  Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. Absolute values for erythrocyte levels are reported in this outcome measure.

  Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

• Stage 1: Change From Baseline in Hematology Parameter - Neutrophil Levels

  Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. CFB in neutrophil levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

• Stage 2: Absolute Values of Hematology Parameter - Neutrophil Levels

  Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. Absolute values for neutrophil levels are reported in this outcome measure.

  Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

• Stage 1: Change From Baseline in Hematology Parameter - Basophil Levels

  Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. CFB in basophil levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

• Stage 2: Absolute Values of Hematology Parameter - Basophil Levels

  Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. Absolute values for basophil levels are reported in this outcome measure.

  Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

• Stage 1: Change From Baseline in Hematology Parameter - Eosinophil Levels

  Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. CFB in eosinophil levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

• Stage 2: Absolute Values of Hematology Parameter - Eosinophil Levels

  Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. Absolute values for eosinophil levels are reported in this outcome measure.

  Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

• Stage 1: Change From Baseline in Hematology Parameter - Monocyte Levels

  Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. CFB in monocyte levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

• Stage 2: Absolute Values of Hematology Parameter - Monocyte Levels

  Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. Absolute values for monocyte levels are reported in this outcome measure.

  Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

• Stage 1: Change From Baseline in Hematology Parameter - Lymphocyte Levels

  Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. CFB in lymphocyte levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

• Stage 2: Absolute Values of Hematology Parameter - Lymphocyte Levels

  Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. Absolute values for lymphocyte levels are reported in this outcome measure.

  Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

• Stage 1: Change From Baseline in Hematology Parameter - Leukocyte Levels

  Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. CFB in leukocyte levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

• Stage 2: Absolute Values of Hematology Parameter - Leukocyte Levels

  Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. Absolute values for leukocyte levels are reported in this outcome measure.

  Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

• Stage 1: Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Volume Levels

  Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. CFB in erythrocytes mean corpuscular volume levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

• Stage 2: Absolute Values of Hematology Parameter - Erythrocytes Mean Corpuscular Volume Levels

  Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. Absolute values for erythrocytes mean corpuscular volume levels are reported in this outcome measure.

  Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

• Stage 1: Change From Baseline in Hematology Parameter - Mean Cell Hemoglobin Levels

  Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. CFB in mean cell hemoglobin levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

• Stage 2: Absolute Values of Hematology Parameter - Mean Cell Hemoglobin

  Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. Absolute values for mean cell hemoglobin levels are reported in this outcome measure.

  Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

• Stage 1: Change From Baseline in Electrocardiogram (ECG) Parameter - QT Interval

  ECG parameters included QT interval, PR interval, QRS duration, QTcB interval, QTcF interval, and heart rate. CFB in QT interval is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 4, 8,12 hours during infusion

• Stage 2: Change From Baseline in ECG Parameter - QT Interval

  ECG parameters included QT interval, PR interval, QRS duration, QTcB interval, QTcF interval, and heart rate. CFB in QT interval is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Stage 2 Day 1: Pre-infusion (Baseline) and 10 hours post-infusion

• Stage 1: Change From Baseline in ECG Parameter - PR Interval

  ECG parameters included QT interval, PR interval, QRS duration, QTcB interval, QTcF interval, and heart rate. CFB in PR interval is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 4, 8,12 hours during infusion

• Stage 2: Change From Baseline in ECG Parameter - PR Interval

  ECG parameters included QT interval, PR interval, QRS duration, QTcB interval, QTcF interval, and heart rate. CFB in PR interval is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Stage 2 Day 1: Pre-infusion (Baseline) and 10 hours post-infusion

• Stage 1: Change From Baseline in ECG Parameter - QRS Duration

  ECG parameters included QT interval, PR interval, QRS duration, QTcB interval, QTcF interval, and heart rate. CFB in QRS duration is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 4, 8, 12 hours during infusion

• Stage 2: Change From Baseline in ECG Parameter - QRS Duration

  ECG parameters included QT interval, PR interval, QRS duration, QTcB interval, QTcF interval, and heart rate. CFB in QRS duration is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Stage 2 Day 1: Pre-infusion (Baseline) and 10 hours post-infusion

• Stage 1: Change From Baseline in ECG Parameter - QTcB Interval

  ECG parameters included QT interval, PR interval, QRS duration, QTcB interval, QTcF interval, and heart rate. CFB in QTcB interval is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 4, 8, 12 hours during infusion

• Stage 2: Change From Baseline in ECG Parameter - QTcB Interval

  ECG parameters included QT interval, PR interval, QRS duration, QTcB interval, QTcF interval, and heart rate. CFB in QTcB interval is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Stage 2 Day 1: Pre-infusion (Baseline) and 10 hours post-infusion

• Stage 1: Change From Baseline in ECG Parameter - QTcF Interval

  ECG parameters included QT interval, PR interval, QRS duration, QTcB interval, QTcF interval, and heart rate. CFB in QTcF interval is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 4, 8, 12 hours during infusion

• Stage 2: Change From Baseline in ECG Parameter - QTcF Interval

  ECG parameters included QT interval, PR interval, QRS duration, QTcB interval, QTcF interval, and heart rate. CFB in QTcF interval is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Stage 2 Day 1: Pre-infusion (Baseline) and 10 hours post-infusion

• Stage 1: Change From Baseline in ECG Parameter - Heart Rate

  ECG parameters included QT interval, PR interval, QRS duration, QTcB interval, QTcF interval, and heart rate. CFB in heart rate is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 4, 8, 12 hours during infusion

• Stage 2: Change From Baseline in ECG Parameter - Heart Rate

  ECG parameters included QT interval, PR interval, QRS duration, QTcB interval, QTcF interval, and heart rate. CFB in heart rate is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

  Stage 2 Day 1: Pre-infusion (Baseline) and 10 hours post-infusion

Secondary Outcomes (18)

• Stage 1: Change From Baseline in Accelerometer Total Score Response

  Stage 1 Days 1 and 10: Pre-infusion (Baseline) and 2, 4, 6, 8, 10 and 12 hours and 12-hour follow-up post-infusion

• Stage 2: Change From Baseline in Accelerometer Total Score Response

  Stage 2 Day 1: Baseline and 2, 3, 4, 6, 8, 10, 12, 14 and 24 hours

• Stage 1: Change From Baseline in The Essential Tremor Rating Scale (TETRAS) Using Performance Subscale (PS) Part 4 Upper-Limb Total Scores

  Stage 1 Days 1 and 10: Pre-infusion (Baseline) and 2, 4, 6, 8, 10 and 12 hours and 12-hour follow-up post-infusion

• Stage 2: Change From Baseline in TETRAS Using PS Part 4 Upper-Limb Total Scores

  Stage 2 Day 1: Baseline and at 2, 3, 4, 6, 8, 10, 12, 14 and 24 hours

• Stage 1: Change From Baseline in Stanford Sleepiness Scale (SSS) Score

  Stage 1 Day 1 and 10: Pre-infusion (Baseline) and 2, 4, 6, 8, 10 and 12 hours and 12-hour follow-up post-infusion

Study Arms (3)

Stage 1 (Double-blind): SAGE 547, Then Placebo

EXPERIMENTAL

Participants received a 12-hour intravenous (IV) infusion of SAGE 547, at ascending doses of 29, 58, and 86 micrograms per kilogram of body weight per hour (μg/kg/h), 4 hours each, on Day 1 of Stage 1 \[Treatment Period 1 (TP 1)\]. After a washout period of approximately 7 days, participants received a 12-hour IV infusion of SAGE-547 matching-placebo, on Day 10 of Stage 1 \[Treatment Period 2 (TP 2)\].

Drug: SAGE-547; Drug: Placebo

Stage 1 (Double-blind): Placebo, Then SAGE-547

EXPERIMENTAL

Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1). After a washout period of approximately 7 days, participants received a 12-hour IV infusion of SAGE 547 at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 10 of Stage 1 (TP 2).

Drug: SAGE-547; Drug: Placebo

Stage 2 (Open Label): SAGE-547

EXPERIMENTAL

Participants who completed Stage 1 were invited to receive a 10-hour IV infusion of SAGE 547, at ascending doses of 90 μg/kg/h for 1 hour, 120 μg/kg/h for 1 hour, and 150 μg/kg/h for 8 hours on Day 1 of Stage 2.

Drug: SAGE-547

Interventions

SAGE-547 DRUG

Stage 1 (Double-blind): Placebo, Then SAGE-547; Stage 1 (Double-blind): SAGE 547, Then Placebo; Stage 2 (Open Label): SAGE-547

Placebo DRUG

Stage 1 (Double-blind): Placebo, Then SAGE-547; Stage 1 (Double-blind): SAGE 547, Then Placebo

Eligibility Criteria

• Age: 35 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females, 35-75 years old with a diagnosis of essential tremor with symptoms clearly present in at least 1 upper limb; participant has had tremor present for at least 2 years prior to Screening
• Off medication, or on a stable dose of medication for their tremor for at least 28 days prior to Screening

You may not qualify if:

• Recent history or active clinically significant manifestations of metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, musculoskeletal, dermatological, urogenital, eyes, ears, nose, or throat, psychiatric, or neurological (other than essential tremor) disorders
• Medical history of seizures

Sponsors & Collaborators

• Sage Therapeutics: lead

Study Sites (2)

Sage Study Site

Bingham Farms, Michigan, United States

Location

Sage Study Site

Raleigh, North Carolina, United States

Location

Related Publications (1)

• Aaron Ellenbogen, Shane Raines, Stephen Kanes. Exploratory trial results for SAGE-547 in essential tremor. Presented at AAN, April 19, 2016 P4.297. MRC-ZUL-00141_Exploratory Trial Results for SAGE-547 in Essential Tremor.

  RESULT

Related Links

• Sage Therapeutics

MeSH Terms

Conditions

Essential Tremor

Interventions

brexanolone

Condition Hierarchy (Ancestors)

Movement Disorders; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: Medical Monitor
• Organization: Sage Therapeutics

info@sagerx.com

(617) 299-8380

Study Officials

• Robert Lasser, MD, MBA

  Sage Therapeutics

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2014
• First Posted: October 28, 2014
• Study Start: September 23, 2014
• Primary Completion: August 14, 2015
• Study Completion: August 14, 2015
• Last Updated: June 29, 2022
• Results First Posted: June 29, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)