The primary objective of this study is to evaluate the safety, tolerability, and plasma pharmacokinetic (PK) of E2511 following multiple oral doses in healthy adult participants.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
DOUBLE
Enrollment
47
California Clinical Trials Medical Group
Glendale, California, United States
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: From Screening up to 14 days after the last dose of study drug (up to 56 days)
Number of Participants With Serious Adverse Events (SAEs)
Time frame: From Screening up to 14 days after the last dose of study drug (up to 56 days)
Number of Participants With Clinically Significant Abnormal Laboratory Values
Time frame: From Screening up to 14 days after the last dose of study drug (up to 56 days)
Number of Participants With Clinically Significant Abnormal Vital Signs Values
Time frame: From Screening up to 14 days after the last dose of study drug (up to 56 days)
Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) Findings
Time frame: From Screening up to 14 days after the last dose of study drug (up to 56 days)
Number of Participants With Clinically Significant Abnormal Ambulatory Blood Pressure
Time frame: From Screening up to 14 days after the last dose of study drug (up to 56 days)
Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-suicide Severity Rating Scale (C-SSRS)
The C-SSRS (mapped to Columbia Classification Algorithm of Suicide Assessment \[C-CASA\]) is an interview-based rating scale to systematically assess any suicidality, suicidal behavior, or suicidal ideation. Any suicidality is emergence of any suicidal ideation or suicidal behavior. Any suicidal behavior is indicated when response is "yes" for any these questions- actual attempt to suicide, engaged in non-suicidal self-injurious behavior, interrupted attempt, aborted attempt, preparatory acts. Any suicidal ideation is indicated when response is "yes" for any of these questions- wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent to suicide.
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Time frame: From Screening up to 14 days after the last dose of study drug (up to 56 days)
Number of Participants With Clinically Significant Abnormal Physical Examination Findings
Time frame: From Screening up to 14 days after the last dose of study drug (up to 56 days)
Number of Participants With Clinically Significant Abnormal Neurological Examination Findings
Time frame: From Screening up to 14 days after the last dose of study drug (up to 56 days)
Number of Participants With Clinically Significant Abnormal Electroencephalogram (EEG) Findings
Time frame: From Screening up to 14 days after the last dose of study drug (up to 56 days)
Cmax: Maximum Observed Plasma Concentration for E2511
Time frame: Day 1: pre-dose up to 24 hours post-dose
Css,max: Maximum Observed Plasma Concentration at Steady State for E2511
Time frame: Day 14: pre-dose up to 24 hours post-dose
tmax: Time to Reach Maximum Observed Plasma Concentration (Cmax) for E2511
Time frame: Day 1: pre-dose up to 24 hours post-dose
tss,max: Time to Reach Maximum Observed Plasma Concentration (Cmax) at Steady State for E2511
Time frame: Day 14: pre-dose up to 24 hours post-dose
Css,av: Average Steady State Plasma Concentration for E2511
Time frame: Day 14: pre-dose up to 24 hours post-dose
AUC(0-t): Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration for E2511
Time frame: Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose
AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time Zero to Infinite for E2511
Time frame: Day 1: pre-dose up to 24 hours post-dose
AUC(0-24h): Area Under the Plasma Concentration-time Curve From Time Zero to 24 hours Post-dose for E2511
Time frame: Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose
t1/2: Terminal Elimination Phase Half-life for E2511
Time frame: Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose
PTF: Peak-trough Fluctuation for E2511
Time frame: Day 14: pre-dose up to 24 hours post-dose
CL/F: Apparent Total Clearance for E2511
Time frame: Day 1: pre-dose up to 24 hours post-dose
CLss/F: Apparent Total Clearance at Steady State for E2511
Time frame: Day 14: pre-dose up to 24 hours post-dose
Vz/F: Apparent Volume of Distribution at Terminal Phase for E2511
Time frame: Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose
Rac: Accumulation Ratio for E2511 Based on Cmax and AUC
Time frame: Day 14: pre-dose up to 24 hours post-dose
Rss: Accumulation Ratio for E2511 Based on Time and Concentration
Time frame: Day 14: pre-dose up to 24 hours post-dose
Change From Baseline in the Concentration of Acetylcholine (ACh) in Cerebrospinal Fluid (CSF)
Time frame: Baseline, Day 13
Change From Baseline in Heart Rate (HR)
Time frame: Baseline up to Day 15
Change From Baseline in PR Interval of the ECG (PR), QRS Interval of the ECG (QRS), and QT Interval Corrected for Heart Rate (QTc) of the ECG
Time frame: Baseline up to Day 15
Placebo Corrected Change From Baseline in HR
Time frame: Baseline up to Day 15
Placebo Corrected Change From Baseline in PR, QRS, and QTc Interval
Time frame: Baseline up to Day 15
Number of Participants With Categorical Outliers for HR, PR, QRS and QTc Interval
Time frame: Baseline up to Day 15
Number of Participants With Treatment-emergent T-wave and U-wave abnormalities
Time frame: Baseline up to Day 15
Mean Change From Baseline in 24-hours Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) up to Day 15
The blood pressure (BP) will be evaluated by Ambulatory Blood Pressure Monitoring (ABPM) for all participants based on the measurement of BP recordings after every 24 hours.
Time frame: Up to Day 15
Mean Change From Baseline in Day-time, Night-time, and Hourly SBP and DBP
Time frame: Baseline up to Day 15
Mean Change From Baseline in Day-time, Night-time, and Hourly HR
Time frame: Baseline up to Day 15
Mean Change From Baseline in Day-time, Night-time, and Hourly Mean Arterial Pressure (MAP) and Pulse Pressure (PP)
Time frame: Baseline up to Day 15
Placebo Corrected Mean Change From Baseline in 24-hours SBP and DBP up to Day 15
The BP will be evaluated by ABPM for all participants based on the measurement of BP recordings after every 24 hours.
Time frame: Up to Day 15
Placebo Corrected Mean Change From Baseline in Day-time, Night-time, and Hourly SBP and DBP
Time frame: Baseline up to Day 15
Placebo Corrected Mean Change From Baseline in Day-time, Night-time, and Hourly HR
Time frame: Baseline up to Day 15
Placebo Corrected Mean Change From Baseline in Day-time, Night-time, and Hourly MAP and PP
Time frame: Baseline up to Day 15
Number of Participants With Categorical Outliers for SBP and DBP
Time frame: Baseline up to Day 15
Geometric Mean Ratio of Cmax Between the Healthy Japanese and Non-japanese Participants for E2511
Time frame: Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose
Geometric Mean Ratio of AUC Between the Healthy Japanese and Non-japanese Participants for E2511
Time frame: Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose
Geometric Mean Ratio of Cmax Between the Younger Non-japanese (>=18 and <55 years) and older Non-japanese (>=55 to <=85 years) Participants for E2511
Time frame: Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose
Geometric Mean Ratio of AUC Between the Younger Non-japanese (>=18 and <55 years) and older Non-japanese (>=55 to <=85 years) Participants for E2511
Time frame: Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose
Geometric Mean Ratio Between the Non-japanese (>=18 and <55 years) and Elderly Non-japanese (>=65 to <=85 years) Participants for E2511
Time frame: Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose