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

NCT05147337 | Completed Phase 1 FDA Drug

• 1 other identifier: E2511-A001-005
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Keywords

E2511; Healthy Participants; Elderly Participants

Outcome Measures

Primary Outcomes (25)

• 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 Outcomes (21)

• 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

Study Arms (8)

Cohort 1: E2511 10 mg or Placebo

EXPERIMENTAL

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; Drug: Placebo

Cohort 2: E2511 20 mg or Placebo

EXPERIMENTAL

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; Drug: Placebo

Cohort 3: E2511 40 mg or Placebo

EXPERIMENTAL

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; Drug: Placebo

Cohort 4: E2511 80 mg or Placebo

EXPERIMENTAL

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; Drug: Placebo

Cohort 5: E2511 20 mg or Placebo

EXPERIMENTAL

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; Drug: Placebo

Cohort 6: E2511 40 mg or Placebo

EXPERIMENTAL

Japanese adult participants will receive 40 mg E2511 or E2511 matched placebo, tablets, orally, once daily from Day 1 to Day 14.

Drug: E2511; Drug: Placebo

Cohort 7: E2511 80 mg or Placebo

EXPERIMENTAL

Japanese adult participants will receive 80 mg E2511 or E2511 matched placebo, tablets, orally, once daily from Day 1 to Day 14.

Drug: E2511; Drug: Placebo

Cohort 8: E2511 40 mg or Placebo

EXPERIMENTAL

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; Drug: Placebo

Interventions

E2511 DRUG

E2511 tablets.

Cohort 1: E2511 10 mg or Placebo; Cohort 2: E2511 20 mg or Placebo; Cohort 3: E2511 40 mg or Placebo; Cohort 4: E2511 80 mg or Placebo; Cohort 5: E2511 20 mg or Placebo; Cohort 6: E2511 40 mg or Placebo; Cohort 7: E2511 80 mg or Placebo; Cohort 8: E2511 40 mg or Placebo

Placebo DRUG

E2511 matched placebo tablets.

Cohort 1: E2511 10 mg or Placebo; Cohort 2: E2511 20 mg or Placebo; Cohort 3: E2511 40 mg or Placebo; Cohort 4: E2511 80 mg or Placebo; Cohort 5: E2511 20 mg or Placebo; Cohort 6: E2511 40 mg or Placebo; Cohort 7: E2511 80 mg or Placebo; Cohort 8: E2511 40 mg or Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (1)

California Clinical Trials Medical Group

Glendale, California, 91206, United States

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2021
• First Posted: December 7, 2021
• Study Start: December 1, 2021
• Primary Completion: August 18, 2022
• Study Completion: August 18, 2022
• Last Updated: September 9, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

US (1)