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

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05147337
• Other study ID #: E2511-A001-005
• Status: Completed
• Phase: Phase 1
• Start date: December 1, 2021
• Est. completion date: August 18, 2022

Study information

• Verified date: March 2022
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: August 18, 2022
• Est. primary completion date: August 18, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• E2511
E2511 tablets.
• Placebo
E2511 matched placebo tablets.

Locations

Country	Name	City	State
United States	California Clinical Trials Medical Group	Glendale	California

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	Cmax: Maximum Observed Plasma Concentration for E2511		Day 1: pre-dose up to 24 hours post-dose
Primary	Css,max: Maximum Observed Plasma Concentration at Steady State for E2511		Day 14: pre-dose up to 24 hours post-dose
Primary	tmax: Time to Reach Maximum Observed Plasma Concentration (Cmax) for E2511		Day 1: pre-dose up to 24 hours post-dose
Primary	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
Primary	Css,av: Average Steady State Plasma Concentration for E2511		Day 14: pre-dose up to 24 hours post-dose
Primary	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
Primary	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
Primary	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
Primary	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
Primary	PTF: Peak-trough Fluctuation for E2511		Day 14: pre-dose up to 24 hours post-dose
Primary	CL/F: Apparent Total Clearance for E2511		Day 1: pre-dose up to 24 hours post-dose
Primary	CLss/F: Apparent Total Clearance at Steady State for E2511		Day 14: pre-dose up to 24 hours post-dose
Primary	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
Primary	Rac: Accumulation Ratio for E2511 Based on Cmax and AUC		Day 14: pre-dose up to 24 hours post-dose
Primary	Rss: Accumulation Ratio for E2511 Based on Time and Concentration		Day 14: pre-dose up to 24 hours post-dose
Secondary	Change From Baseline in the Concentration of Acetylcholine (ACh) in Cerebrospinal Fluid (CSF)		Baseline, Day 13
Secondary	Change From Baseline in Heart Rate (HR)		Baseline up to Day 15
Secondary	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
Secondary	Placebo Corrected Change From Baseline in HR		Baseline up to Day 15
Secondary	Placebo Corrected Change From Baseline in PR, QRS, and QTc Interval		Baseline up to Day 15
Secondary	Number of Participants With Categorical Outliers for HR, PR, QRS and QTc Interval		Baseline up to Day 15
Secondary	Number of Participants With Treatment-emergent T-wave and U-wave abnormalities		Baseline up to Day 15
Secondary	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
Secondary	Mean Change From Baseline in Day-time, Night-time, and Hourly SBP and DBP		Baseline up to Day 15
Secondary	Mean Change From Baseline in Day-time, Night-time, and Hourly HR		Baseline up to Day 15
Secondary	Mean Change From Baseline in Day-time, Night-time, and Hourly Mean Arterial Pressure (MAP) and Pulse Pressure (PP)		Baseline up to Day 15
Secondary	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
Secondary	Placebo Corrected Mean Change From Baseline in Day-time, Night-time, and Hourly SBP and DBP		Baseline up to Day 15
Secondary	Placebo Corrected Mean Change From Baseline in Day-time, Night-time, and Hourly HR		Baseline up to Day 15
Secondary	Placebo Corrected Mean Change From Baseline in Day-time, Night-time, and Hourly MAP and PP		Baseline up to Day 15
Secondary	Number of Participants With Categorical Outliers for SBP and DBP		Baseline up to Day 15
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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