A Study to Assess the Safety and Tolerability of E2511 in Healthy Adult and Elderly Participants

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

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 Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: E2511; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States, 91206
      • California Clinical Trials Medical Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: E2511 10 mg or Placebo; Non-Japanese adult (greater than or equal to [>=] 18 years and less than [<] 55 years old) participants will receive 10 milligram (mg) E2511 or E2511 matched placebo, tablets, orally, once daily from Day 1 to Day 14.	Drug: E2511; E2511 tablets.; Drug: Placebo; E2511 matched placebo tablets.
Experimental: Cohort 2: E2511 20 mg or Placebo; Non-Japanese adult participants will receive 20 mg E2511 or E2511 matched placebo, tablets, orally, once daily from Day 1 to Day 14.	Drug: E2511; E2511 tablets.; Drug: Placebo; E2511 matched placebo tablets.
Experimental: Cohort 3: E2511 40 mg or Placebo; Non-Japanese adult participants will receive 40 mg E2511 or E2511 matched placebo, tablets, orally, once daily from Day 1 to Day 14.	Drug: E2511; E2511 tablets.; Drug: Placebo; E2511 matched placebo tablets.
Experimental: Cohort 4: E2511 80 mg or Placebo; Non-Japanese adult participants will receive 80 mg E2511 or E2511 matched placebo, tablets, orally, once daily from Day 1 to Day 14.	Drug: E2511; E2511 tablets.; Drug: Placebo; E2511 matched placebo tablets.
Experimental: Cohort 5: E2511 20 mg or Placebo; Japanese adult (>=20 years and <55 years old) participants will receive 20 mg E2511 or E2511 matched placebo, tablets, orally, once daily from Day 1 to Day 14.	Drug: E2511; E2511 tablets.; Drug: Placebo; E2511 matched placebo tablets.
Experimental: Cohort 6: E2511 40 mg or Placebo; Japanese adult participants will receive 40 mg E2511 or E2511 matched placebo, tablets, orally, once daily from Day 1 to Day 14.	Drug: E2511; E2511 tablets.; Drug: Placebo; E2511 matched placebo tablets.
Experimental: Cohort 7: E2511 80 mg or Placebo; Japanese adult participants will receive 80 mg E2511 or E2511 matched placebo, tablets, orally, once daily from Day 1 to Day 14.	Drug: E2511; E2511 tablets.; Drug: Placebo; E2511 matched placebo tablets.
Experimental: Cohort 8: E2511 40 mg or Placebo; Non-Japanese older (>=55 years and less than or equal to [<=] 85 years old) participants will receive 40 mg E2511 or E2511 matched placebo, tablets, orally, once daily from Day 1 to Day 14.	Drug: E2511; E2511 tablets.; Drug: Placebo; E2511 matched placebo tablets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs)		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)		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		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		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		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		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.	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		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		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		From Screening up to 14 days after the last dose of study drug (up to 56 days)
Cmax: Maximum Observed Plasma Concentration for E2511		Day 1: pre-dose up to 24 hours post-dose
Css,max: Maximum Observed Plasma Concentration at Steady State for E2511		Day 14: pre-dose up to 24 hours post-dose
tmax: Time to Reach Maximum Observed Plasma Concentration (Cmax) for E2511		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		Day 14: pre-dose up to 24 hours post-dose
Css,av: Average Steady State Plasma Concentration for E2511		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		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		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		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		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		Day 14: pre-dose up to 24 hours post-dose
CL/F: Apparent Total Clearance for E2511		Day 1: pre-dose up to 24 hours post-dose
CLss/F: Apparent Total Clearance at Steady State for E2511		Day 14: pre-dose up to 24 hours post-dose
Vz/F: Apparent Volume of Distribution at Terminal Phase for E2511		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		Day 14: pre-dose up to 24 hours post-dose
Rss: Accumulation Ratio for E2511 Based on Time and Concentration		Day 14: pre-dose up to 24 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Concentration of Acetylcholine (ACh) in Cerebrospinal Fluid (CSF)		Baseline, Day 13
Change From Baseline in Heart Rate (HR)		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		Baseline up to Day 15
Placebo Corrected Change From Baseline in HR		Baseline up to Day 15
Placebo Corrected Change From Baseline in PR, QRS, and QTc Interval		Baseline up to Day 15
Number of Participants With Categorical Outliers for HR, PR, QRS and QTc Interval		Baseline up to Day 15
Number of Participants With Treatment-emergent T-wave and U-wave abnormalities		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.	Up to Day 15
Mean Change From Baseline in Day-time, Night-time, and Hourly SBP and DBP		Baseline up to Day 15
Mean Change From Baseline in Day-time, Night-time, and Hourly HR		Baseline up to Day 15
Mean Change From Baseline in Day-time, Night-time, and Hourly Mean Arterial Pressure (MAP) and Pulse Pressure (PP)		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.	Up to Day 15
Placebo Corrected Mean Change From Baseline in Day-time, Night-time, and Hourly SBP and DBP		Baseline up to Day 15
Placebo Corrected Mean Change From Baseline in Day-time, Night-time, and Hourly HR		Baseline up to Day 15
Placebo Corrected Mean Change From Baseline in Day-time, Night-time, and Hourly MAP and PP		Baseline up to Day 15
Number of Participants With Categorical Outliers for SBP and DBP		Baseline up to Day 15
Geometric Mean Ratio of Cmax Between the Healthy Japanese and Non-japanese Participants for E2511		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		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		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		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		Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose

Collaborators and Investigators

• Sponsor: Eisai Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2021
• Primary Completion (Actual): August 18, 2022
• Study Completion (Actual): August 18, 2022

Study Registration Dates

• First Submitted: November 24, 2021
• First Submitted That Met QC Criteria: November 24, 2021
• First Posted (Actual): December 7, 2021

Study Record Updates

• Last Update Posted (Actual): September 9, 2022
• Last Update Submitted That Met QC Criteria: September 8, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Healthy Participants; E2511; Elderly Participants
• Other Study ID Numbers: E2511-A001-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No