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

• ClinicalTrials.gov Identifier: NCT04547361
• Recruitment Status: Completed
• First Posted: September 14, 2020
• Last Update Posted: July 12, 2021
• Sponsor: Eisai Inc.
• Information provided by (Responsible Party): Eisai Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Healthy Volunteers	Drug: E2511; Drug: E2511 Matched Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 45 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Other
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of E2511 in Healthy Subjects
• Actual Study Start Date: September 14, 2020
• Actual Primary Completion Date: May 26, 2021
• Actual Study Completion Date: May 26, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort 1: Dose 1 E2511 or Placebo; Participants will receive Dose 1 of E2511 or E2511 matched placebo, tablets, orally, once on Day 1 under fasted condition.	Drug: E2511; E2511 tablets.; Drug: E2511 Matched Placebo; Placebo tablets matching E2511 tablets.
Experimental: Cohort 2: Dose 2 E2511 or Placebo; Participants will receive Dose 2 of E2511 or E2511 matched placebo, tablets, orally, once on Day 1 under fasted condition.	Drug: E2511; E2511 tablets.; Drug: E2511 Matched Placebo; Placebo tablets matching E2511 tablets.
Experimental: Cohort 3: Dose 3 E2511 or Placebo; Participants will receive Dose 3 of E2511 or E2511 matched placebo, tablets, orally, once on Day 1 (Treatment Period 1) under fasted condition followed by Dose 3 of E2511 or E2511 matched placebo, tablets, orally, once on Day 7 (Treatment Period 2) under fed condition. A washout period of 6 days will be maintained between the doses.	Drug: E2511; E2511 tablets.; Drug: E2511 Matched Placebo; Placebo tablets matching E2511 tablets.
Experimental: Cohort 4: Dose 4 E2511 or Placebo; Participants will receive Dose 4 of E2511 or E2511 matched placebo, tablets, orally, once on Day 1 under fasted condition.	Drug: E2511; E2511 tablets.; Drug: E2511 Matched Placebo; Placebo tablets matching E2511 tablets.
Experimental: Cohort 5: Dose 5 E2511 or Placebo; Participants will receive Dose 5 of E2511 or E2511 matched placebo, tablets, orally, once on Day 1 under fasted condition.	Drug: E2511; E2511 tablets.; Drug: E2511 Matched Placebo; Placebo tablets matching E2511 tablets.
Experimental: Cohort 6: Dose 6 E2511 or Placebo; Participants will receive Dose 6 of E2511 or E2511 matched placebo, tablets, orally, once on Day 1 under fasted condition.	Drug: E2511; E2511 tablets.; Drug: E2511 Matched Placebo; Placebo tablets matching E2511 tablets.
Experimental: Cohort 7: Dose 3 E2511 (Elderly Participants) or Placebo; Elderly participants will receive Dose 3 of E2511 or E2511 matched placebo, tablets, orally, once on Day 1 under fasted condition.	Drug: E2511; E2511 tablets.; Drug: E2511 Matched Placebo; Placebo tablets matching E2511 tablets.

Outcome Measures

Primary Outcome Measures :

1. 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) [ Time Frame: From screening up to 28 days after last dose of study drug (up to 63 days) ]
2. Cohorts 1, 2, 3, 4, 5, 6, 7: Number of Participants With Markedly Abnormal Laboratory Values [ Time Frame: From screening up to 28 days after last dose of study drug (up to 63 days) ]
3. Cohorts 1, 2, 3, 4, 5, 6, 7: Number of Participants With Clinically Significant Change From Screening in Vital Signs Values [ Time Frame: From screening up to 28 days after last dose of study drug (up to 63 days) ]
4. Cohorts 1, 2, 3, 4, 5, 6, 7: Number of Participants With Clinically Significant Change From Screening in Electrocardiograms (ECGs) Findings [ Time Frame: From screening up to 28 days after last dose of study drug (up to 63 days) ]
5. 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) [ Time Frame: From screening up to 28 days after last dose of study drug (up to 63 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.
6. Cohorts 1, 2, 3, 4, 5, 6, 7: Number of Participants With Clinically Significant Change From Screening in Physical Examination Findings [ Time Frame: From screening up to 28 days after last dose of study drug (up to 63 days) ]
7. Cohorts 1, 2, 3, 4, 5, 6, 7: Number of Participants With Clinically Significant Change From Screening in Neurological Exam Findings [ Time Frame: 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) ]
8. Cohorts 1, 2, 3, 4, 5, 6, 7: Number of Participants With Clinically Significant Change From Screening in Psychiatric Assessment [ Time Frame: From screening up to 28 days after last dose of study drug (up to 63 days) ]
   Number of participants with clinically significant change in psychiatric assessment will be evaluated by a psychiatrist as a measure of mental health assessment.
9. Cohorts 1, 2, 3, 4, 5, 6, 7: Number of Participants With Clinically Significant Change From Screening in Electroencephalogram (EEG) Measurements [ Time Frame: From screening up to Day 2 (approximately 30 days) ]
10. Cohorts 1, 2, 3, 4, 5, 6, 7: Maximum Observed Plasma Concentration (Cmax) for E2511 on Day 1 [ Time Frame: Day 1: pre-dose up to a potential maximum of 120 hours post-dose ]
11. Cohort 3: Maximum Observed Plasma Concentration (Cmax) for E2511 on Day 7 [ Time Frame: Day 7: pre-dose up to a potential maximum of 120 hours post-dose ]
12. Cohorts 1, 2, 3, 4, 5, 6, 7: Time to Reach Cmax (tmax) for E2511 on Day 1 [ Time Frame: Day 1: pre-dose up to a potential maximum of 120 hours post-dose ]
13. Cohort 3: Time to Reach Cmax (tmax) for E2511 on Day 7 [ Time Frame: Day 7: pre-dose up to a potential maximum of 120 hours post-dose ]
14. 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 [ Time Frame: Day 1: pre-dose up to a potential maximum of 120 hours post-dose ]
15. 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 [ Time Frame: Day 7: pre-dose up to a potential maximum of 120 hours post-dose ]
16. 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 [ Time Frame: Day 1: pre-dose up to a potential maximum of 120 hours post-dose ]
17. Cohort 3: Area Under the Plasma Concentration-time Curve (AUC(0-inf)) From Time Zero to Infinity for E2511 on Day 7 [ Time Frame: Day 7: pre-dose up to a potential maximum of 120 hours post-dose ]
18. 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 [ Time Frame: Day 1: pre-dose up to a potential maximum of 24 hours post-dose ]
19. Cohort 3: Area Under the Plasma Concentration-time Curve (AUC(0-24)) From Time Zero to 24 Hours Postdose for E2511 on Day 7 [ Time Frame: Day 7: pre-dose up to a potential maximum of 24 hours post-dose ]
20. Cohorts 1, 2, 3, 4, 5, 6, 7: Terminal Elimination Phase Half-Life (t1/2) for E2511 on Day 1 [ Time Frame: Day 1: pre-dose up to a potential maximum of 120 hours post-dose ]
21. Cohort 3: Terminal Elimination Phase Half-Life (t1/2) for E2511 on Day 7 [ Time Frame: Day 7: pre-dose up to a potential maximum of 120 hours post-dose ]
22. Cohorts 1, 2, 3, 4, 5, 6, 7: Apparent Total Clearance (CL/F) for E2511 on Day 1 [ Time Frame: Day 1: pre-dose up to a potential maximum of 120 hours post-dose ]
23. Cohort 3: Apparent Total Clearance (CL/F) for E2511 on Day 7 [ Time Frame: Day 7: pre-dose up to a potential maximum of 120 hours post-dose ]
24. Cohorts 1, 2, 3, 4, 5, 6, 7: Apparent Volume of Distribution at Terminal Phase (Vz/F) for E2511 on Day 1 [ Time Frame: Day 1: pre-dose up to a potential maximum of 120 hours post-dose ]
25. Cohort 3: Apparent Volume of Distribution at Terminal Phase (Vz/F) for E2511 on Day 7 [ Time Frame: Day 7: pre-dose up to a potential maximum of 120 hours post-dose ]

Secondary Outcome Measures :

1. Cohort 3: Geometric Mean Ratio of Cmax Between the Fasted and Fed State for E2511 20 mg [ Time Frame: Days 1 and 7: pre-dose up to a potential maximum of 120 hours post-dose ]
2. Cohort 3: Geometric Mean Ratio of AUC(0-t) Between the Fasted and fed State for E2511 20 mg [ Time Frame: Days 1 and 7: pre-dose up to a potential maximum of 120 hours post-dose ]
3. Cohort 3: Geometric Mean Ratio of AUC(0-inf) Between the Fasted and fed State for E2511 20 mg [ Time Frame: Days 1 and 7: pre-dose up to a potential maximum of 120 hours post-dose ]
4. Cohort 3 and Cohort 7: Geometric Mean Ratio of Cmax Between the Healthy Elderly and Adult Participants for E2511 20 mg [ Time Frame: 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 ]
5. Cohort 3 and Cohort 7: Geometric Mean Ratio of AUC(0-t) Between the Healthy Elderly and Adult Participants for E2511 20 mg [ Time Frame: 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 ]
6. Cohort 3 and Cohort 7: Geometric Mean Ratio of AUC(0-inf) Between the Healthy Elderly and Adult Participants for E2511 20 mg [ Time Frame: 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 ]
7. Cohorts 1, 2, 3, 4, 5, 6, 7: Correlation Between QTc and E2511 Plasma Concentrations [ Time Frame: Day 1: Pre-dose through 24 hours post dose ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

United States, Texas

Worldwide Clinical Trials

San Antonio, Texas, United States, 78217

Sponsors and Collaborators

Eisai Inc.

More Information

• Responsible Party: Eisai Inc.
• ClinicalTrials.gov Identifier: NCT04547361
• Other Study ID Numbers: E2511-A001-004
• First Posted: September 14, 2020
• Last Update Posted: July 12, 2021
• Last Verified: January 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Eisai Inc.:

E2511; Healthy Participants