Clinical trial NCT02277106: Evaluate SAGE-547 in Participants With Essential Tremor
Official title: A Double-blind, Placebo-controlled, Two-Period Crossover Proof-of-Concept Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of SAGE-547 Injection in the Treatment of Patients With Essential Tremor
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Essential Tremor
Lead sponsor: Sage Therapeutics
Sponsor class: INDUSTRY
First posted: 2014-10-28
Enrollment: 25
Sex: ALL
Minimum age (years): 35
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Stage 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Stage 1: Up to 30 days after last infusion (up to Day 40)
measure: Stage 2: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Stage 2: Up to 30 days after last infusion (up to Day 31)
measure: 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
timeFrame: Stage 1: Pre-infusion on Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2)
measure: 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
timeFrame: Stage 2 Day 1: Pre-infusion and 10 hours and 7-day follow-up post-infusion
measure: Stage 1: Change From Baseline (CFB) in Vital Signs Parameter - Supine Systolic Blood Pressure
timeFrame: 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
measure: Stage 2: Change From Baseline in Vital Signs Parameter - Supine Systolic Blood Pressure
timeFrame: Stage 2 Day 1: Pre-infusion (Baseline) and 2, 4, 6, 8, 10, 12, 14 and 24 hours post-infusion
measure: Stage 1: Change From Baseline in Vital Signs Parameter - Supine Diastolic Blood Pressure
timeFrame: 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
measure: Stage 2: Change From Baseline in Vital Signs Parameter - Supine Diastolic Blood Pressure
timeFrame: Stage 2 Day 1: Pre-infusion (Baseline) and 2, 4, 6, 8, 10, 12, 14 and 24 hours post-infusion
measure: Stage 1: Change From Baseline in Vital Signs Parameter - Supine Heart Rate
timeFrame: 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
measure: Stage 2: Change From Baseline in Vital Signs Parameter - Supine Heart Rate
timeFrame: Stage 2 Day 1: Pre-infusion (Baseline) and 2, 4, 6, 8, 10, 12, 14 and 24 hours post-infusion
measure: Stage 1: Change From Baseline in Vital Signs Parameter - Standing Systolic Blood Pressure
timeFrame: 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
measure: Stage 2: Change From Baseline in Vital Signs Parameter - Standing Systolic Blood Pressure
timeFrame: Stage 2 Day 1: Pre-infusion (Baseline) and 2, 4, 6, 8, 10, 12, 14 and 24 hours post-infusion
measure: Stage 1: Change From Baseline in Vital Signs Parameter - Standing Diastolic Blood Pressure
timeFrame: 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
measure: Stage 2: Change From Baseline in Vital Signs Parameter - Standing Diastolic Blood Pressure
timeFrame: Stage 2 Day 1: Pre-infusion (Baseline) and 2, 4, 6, 8, 10, 12, 14 and 24 hours post-infusion
measure: Stage 1: Change From Baseline in Vital Signs Parameter - Standing Heart Rate
timeFrame: 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
measure: Stage 2: Change From Baseline in Vital Signs Parameter - Standing Heart Rate
timeFrame: Stage 2 Day 1: Pre-infusion (Baseline) and 2, 4, 6, 8, 10, 12, 14 and 24 hours post-infusion
measure: Stage 1: Change From Baseline in Vital Signs Parameter - Temperature
timeFrame: 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
measure: Stage 2: Change From Baseline in Vital Signs Parameter - Temperature
timeFrame: Stage 2 Day 1: Pre-infusion (Baseline) and 2, 4, 6, 8, 10, 12, 14 and 24 hours post-infusion
measure: Stage 1: Change From Baseline in Vital Signs Parameter - Respiratory Rate
timeFrame: 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
measure: Stage 2: Change From Baseline in Vital Signs Parameter - Respiratory Rate
timeFrame: Stage 2 Day 1: Pre-infusion (Baseline) and 2, 4, 6, 8, 10, 12, 14 and 24 hours post-infusion
measure: Stage 1: Change From Baseline in Serum Chemistry Parameter - Alanine Aminotransferase Levels
timeFrame: 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
measure: Stage 2: Absolute Values of Serum Chemistry Parameter - Alanine Aminotransferase Levels
timeFrame: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up
measure: Stage 1: Change From Baseline in Serum Chemistry Parameter - Aspartate Aminotransferase Levels
timeFrame: 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
measure: Stage 2: Absolute Values of Serum Chemistry Parameter - Aspartate Aminotransferase Levels
timeFrame: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up
measure: Stage 1: Change From Baseline in Serum Chemistry Parameter - Gamma Glutamyl Transferase Levels
timeFrame: 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
measure: Stage 2: Absolute Values of Serum Chemistry Parameter - Gamma Glutamyl Transferase Levels
timeFrame: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up
measure: Stage 1: Change From Baseline in Serum Chemistry Parameter - Sodium Levels
timeFrame: 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
measure: Stage 2: Absolute Values of Serum Chemistry Parameter - Sodium Levels
timeFrame: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up
measure: Stage 1: Change From Baseline in Serum Chemistry Parameter - Potassium Levels
timeFrame: 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
measure: Stage 2: Absolute Values of Serum Chemistry Parameter - Potassium Levels
timeFrame: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up
measure: Stage 1: Change From Baseline in Serum Chemistry Parameter - Calcium Levels
timeFrame: 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
measure: Stage 2: Absolute Values of Serum Chemistry Parameter - Calcium Levels
timeFrame: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up
measure: Stage 1: Change From Baseline in Serum Chemistry Parameter - Chloride Levels
timeFrame: 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
measure: Stage 2: Absolute Values of Serum Chemistry Parameter - Chloride Levels
timeFrame: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up
measure: Stage 1: Change From Baseline in Serum Chemistry Parameter - Bicarbonate Levels
timeFrame: 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
measure: Stage 2: Absolute Values of Serum Chemistry Parameter - Bicarbonate Levels
timeFrame: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up
measure: Stage 1: Change From Baseline in Serum Chemistry Parameter - Protein Levels
timeFrame: 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
measure: Stage 2: Absolute Values of Serum Chemistry Parameter - Protein Levels
timeFrame: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up
measure: Stage 1: Change From Baseline in Serum Chemistry Parameter - Glucose Levels
timeFrame: 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
measure: Stage 2: Absolute Values of Serum Chemistry Parameter - Glucose Levels
timeFrame: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up
measure: Stage 1: Change From Baseline in Serum Chemistry Parameter - Lactate Dehydrogenase Levels
timeFrame: 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
measure: Stage 2: Absolute Values of Serum Chemistry Parameter - Lactate Dehydrogenase Levels
timeFrame: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up
measure: Stage 1: Change From Baseline in Serum Chemistry Parameter - Cholesterol Levels
timeFrame: 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
measure: Stage 2: Absolute Values of Serum Chemistry Parameter - Cholesterol Level
timeFrame: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up
measure: Stage 1: Change From Baseline in Serum Chemistry Parameter - Triglyceride Levels
timeFrame: 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
measure: Stage 2: Absolute Values of Serum Chemistry Parameter - Triglyceride Levels
timeFrame: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up
measure: Stage 1: Change From Baseline in Serum Chemistry Parameter - Albumin Levels
timeFrame: 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
measure: Stage 2: Absolute Values of Serum Chemistry Parameter - Albumin Levels
timeFrame: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up
measure: Stage 1: Change From Baseline in Serum Chemistry Parameter - Bilirubin Levels
timeFrame: 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
measure: Stage 2: Absolute Values of Serum Chemistry Parameter - Bilirubin Levels
timeFrame: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up
measure: Stage 1: Change From Baseline in Serum Chemistry Parameter - Creatinine Levels
timeFrame: 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
measure: Stage 2: Absolute Values of Serum Chemistry Parameter - Creatinine Levels
timeFrame: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up
measure: Stage 1: Change From Baseline in Serum Chemistry Parameter - Blood Urea Nitrogen Levels
timeFrame: 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
measure: Stage 2: Absolute Values of Serum Chemistry Parameter - Blood Urea Nitrogen Levels
timeFrame: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up
measure: Stage 1: Change From Baseline in Serum Chemistry Parameter - Alkaline Phosphatase Levels
timeFrame: 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
measure: Stage 2: Absolute Values of Serum Chemistry Parameter - Alkaline Phosphatase Levels
timeFrame: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up
measure: Stage 1: Change From Baseline in Serum Chemistry Parameter - Creatine Kinase Levels
timeFrame: 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
measure: Stage 2: Absolute Values of Serum Chemistry Parameter - Creatine Kinase Levels
timeFrame: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up
measure: Stage 1: Change From Baseline in Serum Chemistry Parameter - Phosphate Levels
timeFrame: 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
measure: Stage 2: Absolute Values of Serum Chemistry Parameter - Phosphate Levels
timeFrame: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up
measure: Stage 1: Change From Baseline in Serum Chemistry Parameter - Urate Levels
timeFrame: 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
measure: Stage 2: Absolute Values of Serum Chemistry Parameter - Urate Levels
timeFrame: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up
measure: Stage 1: Change From Baseline in Hematology Parameter - Hemoglobin Levels
timeFrame: 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
measure: Stage 2: Absolute Values of Hematology Parameter - Hemoglobin Levels
timeFrame: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up
measure: Stage 1: Change From Baseline in Hematology Parameter - Hematocrit Levels
timeFrame: 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
measure: Stage 2: Absolute Values of Hematology Parameter - Hematocrit Levels
timeFrame: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up
measure: Stage 1: Change From Baseline in Hematology Parameter - Platelet Levels
timeFrame: 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
measure: Stage 2: Absolute Values of Hematology Parameter - Platelet Levels
timeFrame: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up
measure: Stage 1: Change From Baseline in Hematology Parameter - Erythrocyte Levels
timeFrame: 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
measure: Stage 2: Absolute Values of Hematology Parameter - Erythrocyte Levels
timeFrame: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up
measure: Stage 1: Change From Baseline in Hematology Parameter - Neutrophil Levels
timeFrame: 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
measure: Stage 2: Absolute Values of Hematology Parameter - Neutrophil Levels
timeFrame: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up
measure: Stage 1: Change From Baseline in Hematology Parameter - Basophil Levels
timeFrame: 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
measure: Stage 2: Absolute Values of Hematology Parameter - Basophil Levels
timeFrame: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up
measure: Stage 1: Change From Baseline in Hematology Parameter - Eosinophil Levels
timeFrame: 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
measure: Stage 2: Absolute Values of Hematology Parameter - Eosinophil Levels
timeFrame: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up
measure: Stage 1: Change From Baseline in Hematology Parameter - Monocyte Levels
timeFrame: 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
measure: Stage 2: Absolute Values of Hematology Parameter - Monocyte Levels
timeFrame: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up
measure: Stage 1: Change From Baseline in Hematology Parameter - Lymphocyte Levels
timeFrame: 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
measure: Stage 2: Absolute Values of Hematology Parameter - Lymphocyte Levels
timeFrame: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up
measure: Stage 1: Change From Baseline in Hematology Parameter - Leukocyte Levels
timeFrame: 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
measure: Stage 2: Absolute Values of Hematology Parameter - Leukocyte Levels
timeFrame: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up
measure: Stage 1: Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Volume Levels
timeFrame: 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
measure: Stage 2: Absolute Values of Hematology Parameter - Erythrocytes Mean Corpuscular Volume Levels
timeFrame: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up
measure: Stage 1: Change From Baseline in Hematology Parameter - Mean Cell Hemoglobin Levels
timeFrame: 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
measure: Stage 2: Absolute Values of Hematology Parameter - Mean Cell Hemoglobin
timeFrame: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up
measure: Stage 1: Change From Baseline in Electrocardiogram (ECG) Parameter - QT Interval
timeFrame: 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
measure: Stage 2: Change From Baseline in ECG Parameter - QT Interval
timeFrame: Stage 2 Day 1: Pre-infusion (Baseline) and 10 hours post-infusion
measure: Stage 1: Change From Baseline in ECG Parameter - PR Interval
timeFrame: 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
measure: Stage 2: Change From Baseline in ECG Parameter - PR Interval
timeFrame: Stage 2 Day 1: Pre-infusion (Baseline) and 10 hours post-infusion
measure: Stage 1: Change From Baseline in ECG Parameter - QRS Duration
timeFrame: 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
measure: Stage 2: Change From Baseline in ECG Parameter - QRS Duration
timeFrame: Stage 2 Day 1: Pre-infusion (Baseline) and 10 hours post-infusion
measure: Stage 1: Change From Baseline in ECG Parameter - QTcB Interval
timeFrame: 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
measure: Stage 2: Change From Baseline in ECG Parameter - QTcB Interval
timeFrame: Stage 2 Day 1: Pre-infusion (Baseline) and 10 hours post-infusion
measure: Stage 1: Change From Baseline in ECG Parameter - QTcF Interval
timeFrame: 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
measure: Stage 2: Change From Baseline in ECG Parameter - QTcF Interval
timeFrame: Stage 2 Day 1: Pre-infusion (Baseline) and 10 hours post-infusion
measure: Stage 1: Change From Baseline in ECG Parameter - Heart Rate
timeFrame: 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
measure: Stage 2: Change From Baseline in ECG Parameter - Heart Rate
timeFrame: Stage 2 Day 1: Pre-infusion (Baseline) and 10 hours post-infusion
Secondary outcomes:
measure: Stage 1: Change From Baseline in Accelerometer Total Score Response
timeFrame: 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
measure: Stage 2: Change From Baseline in Accelerometer Total Score Response
timeFrame: Stage 2 Day 1: Baseline and 2, 3, 4, 6, 8, 10, 12, 14 and 24 hours
measure: Stage 1: Change From Baseline in The Essential Tremor Rating Scale (TETRAS) Using Performance Subscale (PS) Part 4 Upper-Limb Total Scores
timeFrame: 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
measure: Stage 2: Change From Baseline in TETRAS Using PS Part 4 Upper-Limb Total Scores
timeFrame: Stage 2 Day 1: Baseline and at 2, 3, 4, 6, 8, 10, 12, 14 and 24 hours
measure: Stage 1: Change From Baseline in Stanford Sleepiness Scale (SSS) Score
timeFrame: 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
measure: Stage 2: Change From Baseline in Stanford Sleepiness Scale (SSS) Score
timeFrame: Stage 2 Day 1: Baseline and at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours
measure: Stage 1: Maximum Peak Plasma Concentration (Cmax) of SAGE-547
timeFrame: Stage 1: Pre-infusion and after the start of infusion at 30 and 40 minutes and at 1, 1.5, 2, 4, 6, 8, 10, 12, 12.5, 12.75, 13, 13.5, 14, 16 and 24 hours
measure: Stage 2: Maximum Peak Plasma Concentration (Cmax) of SAGE-547
timeFrame: Stage 2: Pre-infusion and at 30, 60, 90 and 120 minutes and at 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 10.5, 10.75, 11, 11.5, 12, 14, 16 and 24 hours after start of the infusion
measure: Stage 1: Time to Maximum Peak Plasma Concentration (Cmax) of SAGE-547
timeFrame: Stage 1: Pre-infusion and after the start of infusion at 30 and 40 minutes and at 1, 1.5, 2, 4, 6, 8, 10, 12, 12.5, 12.75, 13, 13.5, 14, 16 and 24 hours
measure: Stage 2: Time to Maximum Peak Plasma Concentration (Cmax) of SAGE-547
timeFrame: Stage 2: Pre-infusion and at 30, 60, 90 and 120 minutes and at 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 10.5, 10.75, 11, 11.5, 12, 14, 16 and 24 hours after start of the infusion
measure: Stage 1: Area Under the Plasma Concentration Time Curve up to the Time of the Last Quantifiable Sample (AUClast) of SAGE-547
timeFrame: Stage 1: Pre-infusion and after the start of infusion at 30 and 40 minutes and at 1, 1.5, 2, 4, 6, 8, 10, 12, 12.5, 12.75, 13, 13.5, 14, 16 and 24 hours
measure: Stage 2: Area Under the Plasma Concentration Time Curve up to the Time of the Last Quantifiable Sample (AUClast) of SAGE-547
timeFrame: Day 1: Pre-infusion and at 30, 60, 90 and 120 minutes and at 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 10.5, 10.75, 11, 11.5, 12, 14, 16 and 24 hours after start of the infusion
measure: Stage 1: Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of SAGE-547
timeFrame: Stage 1: Pre-infusion and after the start of infusion at 30 and 40 minutes and at 1, 1.5, 2, 4, 6, 8, 10, 12, 12.5, 12.75, 13, 13.5, 14, 16 and 24 hours
measure: Stage 2: Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of SAGE-547
timeFrame: Stage 2: Pre-infusion and at 30, 60, 90 and 120 minutes and at 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 10.5, 10.75, 11, 11.5, 12, 14, 16 and 24 hours after start of the infusion
measure: Stage 1: Clearance (CL) of SAGE-547
timeFrame: Stage 1: Pre-infusion and after the start of infusion at 30 and 40 minutes and at 1, 1.5, 2, 4, 6, 8, 10, 12, 12.5, 12.75, 13, 13.5, 14, 16 and 24 hours
measure: Stage 2: Clearance (CL) of SAGE-547
timeFrame: Stage 2: Pre-infusion and at 30, 60, 90 and 120 minutes and at 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 10.5, 10.75, 11, 11.5, 12, 14, 16 and 24 hours after start of the infusion
measure: Stage 1: Terminal Half-Life (t½) of SAGE-547
timeFrame: Stage 1: Pre-infusion and after the start of infusion at 30 and 40 minutes and at 1, 1.5, 2, 4, 6, 8, 10, 12, 12.5, 12.75, 13, 13.5, 14, 16 and 24 hours
measure: Stage 2: Terminal Half-Life (t½) of SAGE-547
timeFrame: Stage 2: Pre-infusion and at 30, 60, 90 and 120 minutes and at 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 10.5, 10.75, 11, 11.5, 12, 14, 16 and 24 hours after start of the infusion
Other outcomes:
Locations:
city: Bingham Farms
country: United States
facility: Sage Study Site
state: Michigan
city: Raleigh
country: United States
facility: Sage Study Site
state: North Carolina
Study officials:
affiliation: Sage Therapeutics
name: Robert Lasser, MD, MBA
role: STUDY_CHAIR
References:
citation: 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.