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

Healthy Volunteers Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of E2511 in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04547361
• Other study ID #: E2511-A001-004
• Status: Completed
• Phase: Phase 1
• Start date: September 14, 2020
• Est. completion date: May 26, 2021

Study information

• Verified date: January 2021
• 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 pharmacokinetic (PK) of E2511 following single ascending oral doses in healthy adult and elderly participants.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: May 26, 2021
• Est. primary completion date: May 26, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• E2511
E2511 tablets.
• E2511 Matched Placebo
Placebo tablets matching E2511 tablets.

Locations

Country	Name	City	State
United States	Worldwide Clinical Trials	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)		From screening up to 28 days after last dose of study drug (up to 63 days)
Primary	Cohorts 1, 2, 3, 4, 5, 6, 7: Number of Participants With Markedly Abnormal Laboratory Values		From screening up to 28 days after last dose of study drug (up to 63 days)
Primary	Cohorts 1, 2, 3, 4, 5, 6, 7: Number of Participants With Clinically Significant Change From Screening in Vital Signs Values		From screening up to 28 days after last dose of study drug (up to 63 days)
Primary	Cohorts 1, 2, 3, 4, 5, 6, 7: Number of Participants With Clinically Significant Change From Screening in Electrocardiograms (ECGs) Findings		From screening up to 28 days after last dose of study drug (up to 63 days)
Primary	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)	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 28 days after last dose of study drug (up to 63 days)
Primary	Cohorts 1, 2, 3, 4, 5, 6, 7: Number of Participants With Clinically Significant Change From Screening in Physical Examination Findings		From screening up to 28 days after last dose of study drug (up to 63 days)
Primary	Cohorts 1, 2, 3, 4, 5, 6, 7: Number of Participants With Clinically Significant Change From Screening in Neurological Exam Findings		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)
Primary	Cohorts 1, 2, 3, 4, 5, 6, 7: Number of Participants With Clinically Significant Change From Screening in Psychiatric Assessment	Number of participants with clinically significant change in psychiatric assessment will be evaluated by a psychiatrist as a measure of mental health assessment.	From screening up to 28 days after last dose of study drug (up to 63 days)
Primary	Cohorts 1, 2, 3, 4, 5, 6, 7: Number of Participants With Clinically Significant Change From Screening in Electroencephalogram (EEG) Measurements		From screening up to Day 2 (approximately 30 days)
Primary	Cohorts 1, 2, 3, 4, 5, 6, 7: Maximum Observed Plasma Concentration (Cmax) for E2511 on Day 1		Day 1: pre-dose up to a potential maximum of 120 hours post-dose
Primary	Cohort 3: Maximum Observed Plasma Concentration (Cmax) for E2511 on Day 7		Day 7: pre-dose up to a potential maximum of 120 hours post-dose
Primary	Cohorts 1, 2, 3, 4, 5, 6, 7: Time to Reach Cmax (tmax) for E2511 on Day 1		Day 1: pre-dose up to a potential maximum of 120 hours post-dose
Primary	Cohort 3: Time to Reach Cmax (tmax) for E2511 on Day 7		Day 7: pre-dose up to a potential maximum of 120 hours post-dose
Primary	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		Day 1: pre-dose up to a potential maximum of 120 hours post-dose
Primary	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		Day 7: pre-dose up to a potential maximum of 120 hours post-dose
Primary	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		Day 1: pre-dose up to a potential maximum of 120 hours post-dose
Primary	Cohort 3: Area Under the Plasma Concentration-time Curve (AUC(0-inf)) From Time Zero to Infinity for E2511 on Day 7		Day 7: pre-dose up to a potential maximum of 120 hours post-dose
Primary	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		Day 1: pre-dose up to a potential maximum of 24 hours post-dose
Primary	Cohort 3: Area Under the Plasma Concentration-time Curve (AUC(0-24)) From Time Zero to 24 Hours Postdose for E2511 on Day 7		Day 7: pre-dose up to a potential maximum of 24 hours post-dose
Primary	Cohorts 1, 2, 3, 4, 5, 6, 7: Terminal Elimination Phase Half-Life (t1/2) for E2511 on Day 1		Day 1: pre-dose up to a potential maximum of 120 hours post-dose
Primary	Cohort 3: Terminal Elimination Phase Half-Life (t1/2) for E2511 on Day 7		Day 7: pre-dose up to a potential maximum of 120 hours post-dose
Primary	Cohorts 1, 2, 3, 4, 5, 6, 7: Apparent Total Clearance (CL/F) for E2511 on Day 1		Day 1: pre-dose up to a potential maximum of 120 hours post-dose
Primary	Cohort 3: Apparent Total Clearance (CL/F) for E2511 on Day 7		Day 7: pre-dose up to a potential maximum of 120 hours post-dose
Primary	Cohorts 1, 2, 3, 4, 5, 6, 7: Apparent Volume of Distribution at Terminal Phase (Vz/F) for E2511 on Day 1		Day 1: pre-dose up to a potential maximum of 120 hours post-dose
Primary	Cohort 3: Apparent Volume of Distribution at Terminal Phase (Vz/F) for E2511 on Day 7		Day 7: pre-dose up to a potential maximum of 120 hours post-dose
Secondary	Cohort 3: Geometric Mean Ratio of Cmax Between the Fasted and Fed State for E2511 20 mg		Days 1 and 7: pre-dose up to a potential maximum of 120 hours post-dose
Secondary	Cohort 3: Geometric Mean Ratio of AUC(0-t) Between the Fasted and fed State for E2511 20 mg		Days 1 and 7: pre-dose up to a potential maximum of 120 hours post-dose
Secondary	Cohort 3: Geometric Mean Ratio of AUC(0-inf) Between the Fasted and fed State for E2511 20 mg		Days 1 and 7: pre-dose up to a potential maximum of 120 hours post-dose
Secondary	Cohort 3 and Cohort 7: Geometric Mean Ratio of Cmax Between the Healthy Elderly and Adult Participants for E2511 20 mg		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
Secondary	Cohort 3 and Cohort 7: Geometric Mean Ratio of AUC(0-t) Between the Healthy Elderly and Adult Participants for E2511 20 mg		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
Secondary	Cohort 3 and Cohort 7: Geometric Mean Ratio of AUC(0-inf) Between the Healthy Elderly and Adult Participants for E2511 20 mg		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
Secondary	Cohorts 1, 2, 3, 4, 5, 6, 7: Correlation Between QTc and E2511 Plasma Concentrations	To explore the correlation between changes in QTc interval (msec) and E2511 plasma concentrations, appropriate correction method for QTc interval calculation such as QTcF will used for analysis. Holter monitors will be used to collect continuous 12-lead ECG data, from which high precision ECG recordings will be extracted from the Holter monitor data prior to the PK blood samples collected.	Day 1: Pre-dose through 24 hours post dose