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Completed

NCT Number: NCT05147337

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

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.

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Key information

Conditions

Age range

18 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

California Clinical Trials Medical Group

Glendale, California, 91206, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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
  • 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
  • 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

  • Females who are breastfeeding or pregnant at Screening or Baseline
  • 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.
  • Clinically significant illness that requires medical treatment within 8 weeks or a clinically significant infection that requires medical treatment within 4 weeks of dosing
  • 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
  • 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
  • Any personal or family history of seizures (including febrile seizures) or diagnosis of epilepsy or episode of unexplained loss of consciousness
  • Any history of neurological or other medical conditions which in the opinion of the investigator has the potential to reduce seizure threshold
  • Any history of gastrointestinal surgery that may affect PK profiles of E2511, example, hepatectomy, nephrectomy, digestive organ resection at Screening
  • 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
  • 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
  • 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
  • Left bundle branch block
  • History of myocardial infarction or active ischemic heart disease
  • History of clinically significant arrhythmia or uncontrolled arrhythmia
  • Any lifetime history of suicidal ideation or any lifetime history of suicidal behavior as indicated by the C-SSRS
  • Any lifetime history of psychiatric disease

Treatment and study plan

E2511

Drug

E2511 tablets.

Placebo

Drug

E2511 matched placebo tablets.

Primary outcomes

  1. 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)

  2. 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)

  3. 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)

  4. 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)

  5. 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)

  6. 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)

  7. Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-suicide Severity Rating Scale (C-SSRS)

    Time frame: From Screening up to 14 days after the last dose of study drug (up to 56 days)

    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.

  8. 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)

  9. 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)

  10. 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)

  11. Cmax: Maximum Observed Plasma Concentration for E2511

    Time frame: Day 1: pre-dose up to 24 hours post-dose

  12. Css,max: Maximum Observed Plasma Concentration at Steady State for E2511

    Time frame: Day 14: pre-dose up to 24 hours post-dose

  13. tmax: Time to Reach Maximum Observed Plasma Concentration (Cmax) for E2511

    Time frame: Day 1: pre-dose up to 24 hours post-dose

  14. 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

  15. Css,av: Average Steady State Plasma Concentration for E2511

    Time frame: Day 14: pre-dose up to 24 hours post-dose

  16. 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

  17. 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

  18. 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

  19. 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

  20. PTF: Peak-trough Fluctuation for E2511

    Time frame: Day 14: pre-dose up to 24 hours post-dose

  21. CL/F: Apparent Total Clearance for E2511

    Time frame: Day 1: pre-dose up to 24 hours post-dose

  22. CLss/F: Apparent Total Clearance at Steady State for E2511

    Time frame: Day 14: pre-dose up to 24 hours post-dose

  23. 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

  24. Rac: Accumulation Ratio for E2511 Based on Cmax and AUC

    Time frame: Day 14: pre-dose up to 24 hours post-dose

  25. Rss: Accumulation Ratio for E2511 Based on Time and Concentration

    Time frame: Day 14: pre-dose up to 24 hours post-dose

Secondary outcomes

  1. Change From Baseline in the Concentration of Acetylcholine (ACh) in Cerebrospinal Fluid (CSF)

    Time frame: Baseline, Day 13

  2. Change From Baseline in Heart Rate (HR)

    Time frame: Baseline up to Day 15

  3. 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

  4. Placebo Corrected Change From Baseline in HR

    Time frame: Baseline up to Day 15

  5. Placebo Corrected Change From Baseline in PR, QRS, and QTc Interval

    Time frame: Baseline up to Day 15

  6. Number of Participants With Categorical Outliers for HR, PR, QRS and QTc Interval

    Time frame: Baseline up to Day 15

  7. Number of Participants With Treatment-emergent T-wave and U-wave abnormalities

    Time frame: Baseline up to Day 15

  8. Mean Change From Baseline in 24-hours Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) up to Day 15

    Time frame: 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.

  9. Mean Change From Baseline in Day-time, Night-time, and Hourly SBP and DBP

    Time frame: Baseline up to Day 15

  10. Mean Change From Baseline in Day-time, Night-time, and Hourly HR

    Time frame: Baseline up to Day 15

  11. 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

  12. Placebo Corrected Mean Change From Baseline in 24-hours SBP and DBP up to Day 15

    Time frame: 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.

  13. Placebo Corrected Mean Change From Baseline in Day-time, Night-time, and Hourly SBP and DBP

    Time frame: Baseline up to Day 15

  14. Placebo Corrected Mean Change From Baseline in Day-time, Night-time, and Hourly HR

    Time frame: Baseline up to Day 15

  15. Placebo Corrected Mean Change From Baseline in Day-time, Night-time, and Hourly MAP and PP

    Time frame: Baseline up to Day 15

  16. Number of Participants With Categorical Outliers for SBP and DBP

    Time frame: Baseline up to Day 15

  17. 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

  18. 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

  19. 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

  20. 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

  21. 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

Sponsors and collaborators

Lead sponsor

Eisai Inc.

Industry

Registry information

Official study 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

Important dates

Study start
2021
Primary completion
2022
Study completion
2022
First posted
Dec 7, 2021
Registry last updated
Sep 9, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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