Clinical trial NCT04547361: A Study to Assess the Safety and Tolerability of E2511 in Healthy Participants
Official title: A Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of E2511 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: E2511
Healthy Participants
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2020-09-14
Enrollment: 45
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 pharmacokinetic (PK) of E2511 following single ascending oral doses in healthy adult and elderly participants.


Eligibility criteria: Inclusion Criteria:

1. Non-smoking, age greater than or equal to (\>=) 18 years and less than (\<) 55 years old adult male or female (Cohorts 1 - 6) or age \>=65 years and less than or equal to (\<=) 85 years old elderly male or female (Cohort 7) at the time of informed consent
2. Weight of at least 50 kilogram (kg) and body mass index \>=18 and \<30 kilogram per square meter (kg/m\^2) at Screening

Exclusion Criteria:

1. Males who have not had a successful vasectomy (confirmed azoospermia) or they and their female partners do not meet the criteria (that is, not of childbearing potential or practicing highly effective contraception throughout the study period plus 90 days after study drug discontinuation). No sperm donation is allowed during the study period plus 90 days after discharge from the study.
2. Females who are breastfeeding or pregnant at Screening or Baseline
3. 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 (as described above) throughout the entire study period and for 28 days after study drug discontinuation.
4. Clinically significant illness that requires medical treatment within 8 weeks or a clinically significant infection that requires medical treatment within 4 weeks of dosing
5. Evidence of disease that may influence the outcome of the study within 4 weeks before dosing
6. Evidence of disease related to chronic headaches, migraines, joint pain or other disorders or disease resulting in chronic or intermittent pain within 4 weeks before dosing
7. Any personal or family history of seizures (including febrile seizures) or diagnosis of epilepsy or episode of unexplained loss of consciousness
8. Any history of neurological or other medical conditions which in the opinion of the investigator has the potential to reduce seizure threshold
9. Any epileptiform discharges in EEG at Screening
10. A prolonged QT/ QT interval corrected for heart rate (QTc) interval \>450 millisecond \[ms\]) A history of risk factors for torsade de pointes
11. History of prolonged QT/QTc interval
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: Cohorts 1, 2, 3, 4, 5, 6, 7: Number of Participants Reporting one or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: From screening up to 28 days after last dose of study drug (up to 63 days)
measure: Cohorts 1, 2, 3, 4, 5, 6, 7: Number of Participants With Markedly Abnormal Laboratory Values
timeFrame: From screening up to 28 days after last dose of study drug (up to 63 days)
measure: Cohorts 1, 2, 3, 4, 5, 6, 7: Number of Participants With Clinically Significant Change From Screening in Vital Signs Values
timeFrame: From screening up to 28 days after last dose of study drug (up to 63 days)
measure: Cohorts 1, 2, 3, 4, 5, 6, 7: Number of Participants With Clinically Significant Change From Screening in Electrocardiograms (ECGs) Findings
timeFrame: From screening up to 28 days after last dose of study drug (up to 63 days)
measure: Cohorts 1, 2, 3, 4, 5, 6, 7: Number of Participants With Treatment-emergent Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: From screening up to 28 days after last dose of study drug (up to 63 days)
measure: Cohorts 1, 2, 3, 4, 5, 6, 7: Number of Participants With Clinically Significant Change From Screening in Physical Examination Findings
timeFrame: From screening up to 28 days after last dose of study drug (up to 63 days)
measure: Cohorts 1, 2, 3, 4, 5, 6, 7: Number of Participants With Clinically Significant Change From Screening in Neurological Exam Findings
timeFrame: Cohorts 1, 2, 4, 5, 6, 7: Screening up to Day 1 (approximately 28 days); Cohort 3: Screening up to Day 7 (approximately 35 days)
measure: Cohorts 1, 2, 3, 4, 5, 6, 7: Number of Participants With Clinically Significant Change From Screening in Psychiatric Assessment
timeFrame: From screening up to 28 days after last dose of study drug (up to 63 days)
measure: Cohorts 1, 2, 3, 4, 5, 6, 7: Number of Participants With Clinically Significant Change From Screening in Electroencephalogram (EEG) Measurements
timeFrame: From screening up to Day 2 (approximately 30 days)
measure: Cohorts 1, 2, 3, 4, 5, 6, 7: Maximum Observed Plasma Concentration (Cmax) for E2511 on Day 1
timeFrame: Day 1: pre-dose up to a potential maximum of 120 hours post-dose
measure: Cohort 3: Maximum Observed Plasma Concentration (Cmax) for E2511 on Day 7
timeFrame: Day 7: pre-dose up to a potential maximum of 120 hours post-dose
measure: Cohorts 1, 2, 3, 4, 5, 6, 7: Time to Reach Cmax (tmax) for E2511 on Day 1
timeFrame: Day 1: pre-dose up to a potential maximum of 120 hours post-dose
measure: Cohort 3: Time to Reach Cmax (tmax) for E2511 on Day 7
timeFrame: Day 7: pre-dose up to a potential maximum of 120 hours post-dose
measure: Cohorts 1, 2, 3, 4, 5, 6, 7: Area Under the Plasma Concentration-time Curve (AUC(0-t)) From Time Zero to the Last Quantifiable Plasma Concentration for E2511 on Day 1
timeFrame: Day 1: pre-dose up to a potential maximum of 120 hours post-dose
measure: Cohort 3: Area Under the Plasma Concentration-time Curve (AUC(0-t)) From Time Zero to the Last Quantifiable Plasma Concentration for E2511 on Day 7
timeFrame: Day 7: pre-dose up to a potential maximum of 120 hours post-dose
measure: Cohorts 1, 2, 3, 4, 5, 6, 7: Area Under the Plasma Concentration-time Curve (AUC(0-inf)) From Time Zero to Infinity for E2511 on Day 1
timeFrame: Day 1: pre-dose up to a potential maximum of 120 hours post-dose
measure: Cohort 3: Area Under the Plasma Concentration-time Curve (AUC(0-inf)) From Time Zero to Infinity for E2511 on Day 7
timeFrame: Day 7: pre-dose up to a potential maximum of 120 hours post-dose
measure: Cohorts 1, 2, 3, 4, 5, 6, 7: Area Under the Plasma Concentration-time Curve (AUC(0-24)) From Time Zero to 24 Hours Postdose for E2511 on Day 1
timeFrame: Day 1: pre-dose up to a potential maximum of 24 hours post-dose
measure: Cohort 3: Area Under the Plasma Concentration-time Curve (AUC(0-24)) From Time Zero to 24 Hours Postdose for E2511 on Day 7
timeFrame: Day 7: pre-dose up to a potential maximum of 24 hours post-dose
measure: Cohorts 1, 2, 3, 4, 5, 6, 7: Terminal Elimination Phase Half-Life (t1/2) for E2511 on Day 1
timeFrame: Day 1: pre-dose up to a potential maximum of 120 hours post-dose
measure: Cohort 3: Terminal Elimination Phase Half-Life (t1/2) for E2511 on Day 7
timeFrame: Day 7: pre-dose up to a potential maximum of 120 hours post-dose
measure: Cohorts 1, 2, 3, 4, 5, 6, 7: Apparent Total Clearance (CL/F) for E2511 on Day 1
timeFrame: Day 1: pre-dose up to a potential maximum of 120 hours post-dose
measure: Cohort 3: Apparent Total Clearance (CL/F) for E2511 on Day 7
timeFrame: Day 7: pre-dose up to a potential maximum of 120 hours post-dose
measure: Cohorts 1, 2, 3, 4, 5, 6, 7: Apparent Volume of Distribution at Terminal Phase (Vz/F) for E2511 on Day 1
timeFrame: Day 1: pre-dose up to a potential maximum of 120 hours post-dose
measure: Cohort 3: Apparent Volume of Distribution at Terminal Phase (Vz/F) for E2511 on Day 7
timeFrame: Day 7: pre-dose up to a potential maximum of 120 hours post-dose
Secondary outcomes:
measure: Cohort 3: Geometric Mean Ratio of Cmax Between the Fasted and Fed State for E2511 20 mg
timeFrame: Days 1 and 7: pre-dose up to a potential maximum of 120 hours post-dose
measure: Cohort 3: Geometric Mean Ratio of AUC(0-t) Between the Fasted and fed State for E2511 20 mg
timeFrame: Days 1 and 7: pre-dose up to a potential maximum of 120 hours post-dose
measure: Cohort 3: Geometric Mean Ratio of AUC(0-inf) Between the Fasted and fed State for E2511 20 mg
timeFrame: Days 1 and 7: pre-dose up to a potential maximum of 120 hours post-dose
measure: Cohort 3 and Cohort 7: Geometric Mean Ratio of Cmax Between the Healthy Elderly and Adult Participants for E2511 20 mg
timeFrame: Cohort 3: Days 1 and 7: pre-dose up to a potential maximum of 120 hours post-dose; Cohort 7: Day 1: pre-dose up to a potential maximum of 120 hours post-dose
measure: Cohort 3 and Cohort 7: Geometric Mean Ratio of AUC(0-t) Between the Healthy Elderly and Adult Participants for E2511 20 mg
timeFrame: Cohort 3: Days 1 and 7: pre-dose up to a potential maximum of 120 hours post-dose; Cohort 7: Day 1: pre-dose up to a potential maximum of 120 hours post-dose
measure: Cohort 3 and Cohort 7: Geometric Mean Ratio of AUC(0-inf) Between the Healthy Elderly and Adult Participants for E2511 20 mg
timeFrame: Cohort 3: Days 1 and 7: pre-dose up to a potential maximum of 120 hours post-dose; Cohort 7: Day 1: pre-dose up to a potential maximum of 120 hours post-dose
measure: Cohorts 1, 2, 3, 4, 5, 6, 7: Correlation Between QTc and E2511 Plasma Concentrations
timeFrame: Day 1: Pre-dose through 24 hours post dose
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Worldwide Clinical Trials
state: Texas
Study officials:
References: