A Study To Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of E2086 in Healthy Adult and Elderly Participants

NCT05745207 | Completed Phase 1 FDA Drug

• 1 other identifier: E2086-A001-001
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to evaluate the safety and tolerability of E2086 following administration of a single oral doses in healthy adult and elderly participants.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (9)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs)

  From Screening up to 10 days

• Number of Participants With Serious Adverse Events (SAEs)

  From Screening up to 10 days

• Number of Participants With Clinically Significant Abnormal Laboratory Values

  From Screening up to 10 days

• Number of Participants With Clinically Significant Abnormal Vital Signs Values

  From Screening up to 10 days

• Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) Findings

  From Screening up to 10 days

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

  The C-SSRS 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 10 days

• Number of Participants With Clinically Significant Abnormal Physical Examination Findings

  From Screening up to 10 days

• Number of Participants With Clinically Significant Abnormal Neurological Examination Findings

  From Screening up to 10 days

• Number of Participants With Clinically Significant Abnormal Electroencephalogram (EEG) Findings

  Baseline, Days 1 and 2

Secondary Outcomes (15)

• Cmax: Maximum Observed Plasma Concentration for E2086 and its Metabolites

  Day 1: Pre-dose (0 hour) up to 216 hours post-dose

• Tmax: Time to Reach Maximum Observed Plasma Concentration (Cmax) for E2086 and its Metabolites

  Day 1: Pre-dose (0 hour) up to 216 hours post-dose

• AUC(0-24h): Area Under the Plasma Concentration-time Curve From Time Zero to 24 hours Post-dose for E2086 and its Metabolites

  Day 1: Pre-dose (0 hour) 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 E2086 and its Metabolites

  Day 1: Pre-dose (0 hour) up to 216 hours post-dose

• AUC(0-72h): Area Under the Plasma Concentration-time Curve From Time Zero to 72 hours Post-dose for E2086 and its Metabolites

  Day 1: Pre-dose (0 hour) up to 72 hours post-dose

Study Arms (8)

Part A, Cohort 1: E2086 1 mg or Placebo

EXPERIMENTAL

Participants will receive 1 milligram (mg) (2\*0.5 mg) E2086 or E2086 matched placebo, tablets, orally, once on Day 1.

Drug: E2086; Drug: Placebo

Part A, Cohort 2: E2086 2.5 mg or Placebo

EXPERIMENTAL

Participants will receive 2.5 mg (5\*0.5 mg) E2086 or E2086 matched placebo, tablets, orally, once on Day 1.

Drug: E2086; Drug: Placebo

Part A, Cohort 3: E2086 5 mg or Placebo

EXPERIMENTAL

Participants will receive 5 mg (1\*5 mg) E2086 or E2086 matched placebo, tablets, orally, once on Day 1.

Drug: E2086; Drug: Placebo

Part A, Cohort 4: E2086 10 mg or Placebo

EXPERIMENTAL

Participants will receive 10 mg (2\*5 mg) E2086 or E2086 matched placebo, tablets, orally, once on Day 1.

Drug: E2086; Drug: Placebo

Part A, Cohort 5: E2086 25 mg or Placebo

EXPERIMENTAL

Participants will receive 25 mg (1\*25 mg) E2086 or E2086 matched placebo, tablets, orally, once on Day 1.

Drug: E2086; Drug: Placebo

Part A, Cohort 6: E2086 50 mg or Placebo

EXPERIMENTAL

Participants will receive 50 mg (2\*25 mg) E2086 or E2086 matched placebo, tablets, orally, once on Day 1.

Drug: E2086; Drug: Placebo

Part A, Cohort 7: E2086 100 mg or Placebo

EXPERIMENTAL

Participants will receive 100 mg (4\*25 mg) E2086 or E2086 matched placebo, tablets, orally, once on Day 1.

Drug: E2086; Drug: Placebo

Part B, Cohort 8: E2086 25 mg or Placebo

EXPERIMENTAL

Participants will receive 25 mg (1\*25 mg) E2086 or E2086 matched placebo, tablets, orally, once on Day 1.

Drug: E2086; Drug: Placebo

Interventions

E2086 DRUG

E2086 tablets.

Part A, Cohort 1: E2086 1 mg or Placebo; Part A, Cohort 2: E2086 2.5 mg or Placebo; Part A, Cohort 3: E2086 5 mg or Placebo; Part A, Cohort 4: E2086 10 mg or Placebo; Part A, Cohort 5: E2086 25 mg or Placebo; Part A, Cohort 6: E2086 50 mg or Placebo; Part A, Cohort 7: E2086 100 mg or Placebo; Part B, Cohort 8: E2086 25 mg or Placebo

Placebo DRUG

E2086 matched placebo tablets.

Part A, Cohort 1: E2086 1 mg or Placebo; Part A, Cohort 2: E2086 2.5 mg or Placebo; Part A, Cohort 3: E2086 5 mg or Placebo; Part A, Cohort 4: E2086 10 mg or Placebo; Part A, Cohort 5: E2086 25 mg or Placebo; Part A, Cohort 6: E2086 50 mg or Placebo; Part A, Cohort 7: E2086 100 mg or Placebo; Part B, Cohort 8: E2086 25 mg or Placebo

Eligibility Criteria

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

You may qualify if:

• Non-smoking, male or female, age greater than or equal to (\>=) 18 years to less than or equal to (\<=) 55 years old (greater than \[\>\] 65 years old for Part B) at the time of informed consent. To be considered non-smokers, participants must have discontinued smoking for at least 4 weeks before dosing.
• Reports regular bedtime, defined as the time the participant attempts to sleep, between 21:00 and midnight, based on sleep diary data from the Screening Period.
• Reports regular waketime, defined as the time the participant gets out of bed for the day, between 05:00 and 10:00, based on sleep diary data from the Screening Period.
• Body mass index (BMI) \>=18 to less than (\<) 30 kilogram per square meter (kg/m\^2) at Screening.

You may not qualify if:

• Clinically significant illness that requires medical treatment within 8 weeks or a clinically significant infection that requires medical treatment within 4 weeks of dosing
• Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin \[ß-hCG\] (or human chorionic gonadotropin \[hCG\]) test with a minimum sensitivity of 25 international units per liter (IU/L) or equivalent units of ß-hCG \[or hCG\]). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the dose of study drug.
• All females who are of childbearing potential:
• All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (that is, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing).
• Males who have not had a successful vasectomy (confirmed azoospermia) or they and their female partners do not meet the criteria above (that is, not of childbearing potential or practicing highly effective contraception throughout the study period or for 28 days after study drug discontinuation). No sperm donation is allowed during the study period or for 90 days after study drug discontinuation
• 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)
• Any history of a congenital abnormality in metabolism at Screening
• Any history of seizure, epilepsy, or non-epileptic seizures
• Any history of surgery that may affect PK profiles of E2086 (example, hepatectomy, nephrotomy, digestive organ resection) at Screening
• Any clinically abnormal symptom or organ impairment found by medical history, physical examinations, vital signs, ECG finding, or laboratory test results that require medical treatment at Screening or Baseline
• Liver function test values outside of the normal laboratory defined range at Screening or Baseline.
• Any history of liver disease.
• Known history of liver function test values outside of the normal laboratory defined range within the last 6 months.
• Evidence of clinically significant disease (example, cardiac, respiratory, gastrointestinal, renal disease, sleep disorders) that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments
• A prolonged QT/QTc interval (QTc \>450 milliseconds \[ms\]) demonstrated on ECG at Screening or Baseline (based on average of triplicate ECGs). A history of risk factors for torsade de pointes (example, heart failure, hypokalemia, family history of long QT Syndrome) or the use of concomitant medications that prolonged the QT/QTc interval

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (1)

Worldwide Clinical Trials

San Antonio, Texas, 78217, United States

Location

Study Design

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

Study Record Dates

• First Submitted: February 16, 2023
• First Posted: February 27, 2023
• Study Start: February 20, 2023
• Primary Completion: January 18, 2024
• Study Completion: January 18, 2024
• Last Updated: October 2, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share

Locations

US (1)