Clinical trial NCT05147337: A Study to Assess the Safety and Tolerability of E2511 in Healthy Adult and Elderly Participants
Official title: A Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of E2511 in Healthy Adult and Elderly Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: E2511
Healthy Participants
Elderly Participants
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2021-12-07
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Non-smoking, male, or female, non-Japanese participants age \>=18 years and \<55 years old (Cohorts 1 to 4) or age \>=55 years and \<=85 years old (Cohort 8); or Japanese participants age \>=20 years and \<55 years old (Cohorts 5 to 7) at the time of informed consent
2. Japanese participants must also satisfy the following requirements:

   * Must have been born in Japan of Japanese parents and Japanese grandparents
   * Must have lived no more than 5 years outside of Japan
   * Must not have changed their lifestyle or habits, including diet, while living outside of Japan
3. Weight of at least 50 kilogram (kg) and body mass index (BMI) \>=18 and \<30 kilogram per square meter (kg/m\^2) (Cohorts 1 to 7) or BMI \>=18 and \<32 kg/m\^2 (Cohort 8) at Screening

Exclusion Criteria:

1. Females who are breastfeeding or pregnant at Screening or Baseline
2. Females of childbearing potential who:

   * Within 28 days before study entry, did not use a highly effective method of contraception
   * Do not agree to use a highly effective method of contraception throughout the entire study period and for 28 days after study drug discontinuation.
3. Clinically significant illness that requires medical treatment within 8 weeks or a clinically significant infection that requires medical treatment within 4 weeks of dosing
4. Evidence of disease that may influence the outcome of the study within 4 weeks before dosing; example, psychiatric disorders and disorders of the gastrointestinal tract, liver, kidney, respiratory system, endocrine system, hematological system, neurological system, or cardiovascular system, or participants who have a congenital abnormality in metabolism
5. Evidence of disease within 4 weeks before dosing related to chronic headaches, migraines, joint pain, or other disorders or disease resulting in chronic or intermittent pain
6. Any personal or family history of seizures (including febrile seizures) or diagnosis of epilepsy or episode of unexplained loss of consciousness
7. Any history of neurological or other medical conditions which in the opinion of the investigator has the potential to reduce seizure threshold
8. Any history of gastrointestinal surgery that may affect PK profiles of E2511, example, hepatectomy, nephrectomy, digestive organ resection at Screening
9. Any clinically abnormal symptom or organ impairment found by medical history at Screening, and physical examinations, vital signs, ECG finding, or laboratory test results that require medical treatment at Screening or Baseline
10. A prolonged QT/QT interval corrected for heart rate (QTc) interval or a prolonged QT/QTc interval (QT interval corrected for heart rate using Fridericia's formula \[QTcF\] greater than \[\>\] 450 milliseconds \[ms\]). A history of risk factors for torsade de pointes
11. HR \<50 or more than 100 beats per minute at Screening or Baseline (Cohorts 1 through 7); or HR \<55 or more than 100 beats per minute at Screening or Baseline (Cohort 8) NOTE: At Baseline, HR must meet the above criteria on 3 assessments (each separated by 15 minutes) to ensure eligibility
12. Left bundle branch block
13. History of myocardial infarction or active ischemic heart disease
14. History of clinically significant arrhythmia or uncontrolled arrhythmia
15. Any lifetime history of suicidal ideation or any lifetime history of suicidal behavior as indicated by the C-SSRS
16. Any lifetime history of psychiatric disease

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From Screening up to 14 days after the last dose of study drug (up to 56 days)
measure: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: From Screening up to 14 days after the last dose of study drug (up to 56 days)
measure: Number of Participants With Clinically Significant Abnormal Laboratory Values
timeFrame: From Screening up to 14 days after the last dose of study drug (up to 56 days)
measure: Number of Participants With Clinically Significant Abnormal Vital Signs Values
timeFrame: From Screening up to 14 days after the last dose of study drug (up to 56 days)
measure: Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) Findings
timeFrame: From Screening up to 14 days after the last dose of study drug (up to 56 days)
measure: Number of Participants With Clinically Significant Abnormal Ambulatory Blood Pressure
timeFrame: From Screening up to 14 days after the last dose of study drug (up to 56 days)
measure: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-suicide Severity Rating Scale (C-SSRS)
timeFrame: From Screening up to 14 days after the last dose of study drug (up to 56 days)
measure: Number of Participants With Clinically Significant Abnormal Physical Examination Findings
timeFrame: From Screening up to 14 days after the last dose of study drug (up to 56 days)
measure: Number of Participants With Clinically Significant Abnormal Neurological Examination Findings
timeFrame: From Screening up to 14 days after the last dose of study drug (up to 56 days)
measure: Number of Participants With Clinically Significant Abnormal Electroencephalogram (EEG) Findings
timeFrame: From Screening up to 14 days after the last dose of study drug (up to 56 days)
measure: Cmax: Maximum Observed Plasma Concentration for E2511
timeFrame: Day 1: pre-dose up to 24 hours post-dose
measure: Css,max: Maximum Observed Plasma Concentration at Steady State for E2511
timeFrame: Day 14: pre-dose up to 24 hours post-dose
measure: tmax: Time to Reach Maximum Observed Plasma Concentration (Cmax) for E2511
timeFrame: Day 1: pre-dose up to 24 hours post-dose
measure: tss,max: Time to Reach Maximum Observed Plasma Concentration (Cmax) at Steady State for E2511
timeFrame: Day 14: pre-dose up to 24 hours post-dose
measure: Css,av: Average Steady State Plasma Concentration for E2511
timeFrame: Day 14: pre-dose up to 24 hours post-dose
measure: AUC(0-t): Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration for E2511
timeFrame: Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose
measure: AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time Zero to Infinite for E2511
timeFrame: Day 1: pre-dose up to 24 hours post-dose
measure: AUC(0-24h): Area Under the Plasma Concentration-time Curve From Time Zero to 24 hours Post-dose for E2511
timeFrame: Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose
measure: t1/2: Terminal Elimination Phase Half-life for E2511
timeFrame: Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose
measure: PTF: Peak-trough Fluctuation for E2511
timeFrame: Day 14: pre-dose up to 24 hours post-dose
measure: CL/F: Apparent Total Clearance for E2511
timeFrame: Day 1: pre-dose up to 24 hours post-dose
measure: CLss/F: Apparent Total Clearance at Steady State for E2511
timeFrame: Day 14: pre-dose up to 24 hours post-dose
measure: Vz/F: Apparent Volume of Distribution at Terminal Phase for E2511
timeFrame: Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose
measure: Rac: Accumulation Ratio for E2511 Based on Cmax and AUC
timeFrame: Day 14: pre-dose up to 24 hours post-dose
measure: Rss: Accumulation Ratio for E2511 Based on Time and Concentration
timeFrame: Day 14: pre-dose up to 24 hours post-dose
Secondary outcomes:
measure: Change From Baseline in the Concentration of Acetylcholine (ACh) in Cerebrospinal Fluid (CSF)
timeFrame: Baseline, Day 13
measure: Change From Baseline in Heart Rate (HR)
timeFrame: Baseline up to Day 15
measure: 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
timeFrame: Baseline up to Day 15
measure: Placebo Corrected Change From Baseline in HR
timeFrame: Baseline up to Day 15
measure: Placebo Corrected Change From Baseline in PR, QRS, and QTc Interval
timeFrame: Baseline up to Day 15
measure: Number of Participants With Categorical Outliers for HR, PR, QRS and QTc Interval
timeFrame: Baseline up to Day 15
measure: Number of Participants With Treatment-emergent T-wave and U-wave abnormalities
timeFrame: Baseline up to Day 15
measure: Mean Change From Baseline in 24-hours Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) up to Day 15
timeFrame: Up to Day 15
measure: Mean Change From Baseline in Day-time, Night-time, and Hourly SBP and DBP
timeFrame: Baseline up to Day 15
measure: Mean Change From Baseline in Day-time, Night-time, and Hourly HR
timeFrame: Baseline up to Day 15
measure: Mean Change From Baseline in Day-time, Night-time, and Hourly Mean Arterial Pressure (MAP) and Pulse Pressure (PP)
timeFrame: Baseline up to Day 15
measure: Placebo Corrected Mean Change From Baseline in 24-hours SBP and DBP up to Day 15
timeFrame: Up to Day 15
measure: Placebo Corrected Mean Change From Baseline in Day-time, Night-time, and Hourly SBP and DBP
timeFrame: Baseline up to Day 15
measure: Placebo Corrected Mean Change From Baseline in Day-time, Night-time, and Hourly HR
timeFrame: Baseline up to Day 15
measure: Placebo Corrected Mean Change From Baseline in Day-time, Night-time, and Hourly MAP and PP
timeFrame: Baseline up to Day 15
measure: Number of Participants With Categorical Outliers for SBP and DBP
timeFrame: Baseline up to Day 15
measure: Geometric Mean Ratio of Cmax Between the Healthy Japanese and Non-japanese Participants for E2511
timeFrame: Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose
measure: Geometric Mean Ratio of AUC Between the Healthy Japanese and Non-japanese Participants for E2511
timeFrame: Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose
measure: 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
timeFrame: Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose
measure: 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
timeFrame: Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose
measure: Geometric Mean Ratio Between the Non-japanese (>=18 and <55 years) and Elderly Non-japanese (>=65 to <=85 years) Participants for E2511
timeFrame: Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose
Other outcomes:
Locations:
city: Glendale
country: United States
facility: California Clinical Trials Medical Group
state: California
Study officials:
References: