Clinical trial NCT04683185: A Study to Assess the Safety and Tolerability of E6742 in Japanese Healthy Adult Participants
Official title: A Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of E6742 in Japanese Healthy Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: E6742
Healthy participants
Pharmacokinetics
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2020-12-24
Enrollment: 24
Sex: ALL
Minimum age (years): 20
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The primary purpose of the study is to evaluate the safety, tolerability and pharmacokinetics (PK) of multiple ascending oral doses of E6742 in Japanese healthy adult participants.


Eligibility criteria: Inclusion Criteria:

1. Non-smoking, male or female Japanese, greater than or equal to (\>=) age 20 years and less than or equal to (\<=) 55 years old at the time of informed consent
2. Body mass index (BMI) \>=18.5 and less than (\<) 25.0 kilogram per meter square (kg/m\^2) at Screening

Exclusion Criteria:

1. Females who are breastfeeding or pregnant at Screening or Baseline
2. Females of childbearing potential who:

   * Within 28 days before study entry, did not use a highly effective method of contraception, which includes any of the following:

     * Total abstinence
     * An intrauterine device (IUD) or intrauterine hormone-releasing system (IUS)
     * A contraceptive implant
     * An oral contraceptive
     * Have a vasectomized partner with confirmed azoospermia
   * 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
3. 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 and for 5 times the half-life of the study drug plus 90 days after study drug discontinuation)
4. Clinically significant illness that requires medical treatment within 8 weeks or a clinically significant infection within 4 weeks before dosing
5. Any history of gastrointestinal surgery that may affect PK profiles of E6742 at Screening
6. Any clinically abnormal symptom or organ impairment found by medical history, ophthalmic examination or chest X ray test at Screening, or founded by physical examinations, vital signs, ECG finding, or laboratory test results at Screening or Baseline
7. A prolonged QTc corrected using Fridericia's method (QTcF) interval (QTcF greater than \[\>\] 450 millisecond \[ms\]) demonstrated on ECG at Screening or Baseline. A history of risk factors for torsade de pointes or the use of concomitant medications that prolonged the QT/QTc interval
8. Persistent systolic blood pressure \>130 millimeter of mercury (mmHg) or diastolic blood pressure \>85 mmHg diastolic at Screening or Baseline
9. Heart rate less than 45 or more than 100 beats per min at Screening or Baseline
10. Any lifetime history of suicidal ideation or any lifetime history of suicidal behavior as indicated by the Suicidal Ideation section of the Columbia Suicide Severity Rating Scale (C-SSRS)
11. Any lifetime history of psychiatric disease
12. Any current psychiatric symptoms as indicated by a standard screening tool (Patient Health Questionnaire 9 \[PHQ 9\])
13. Any suicidal ideation with intent with or without a plan within Screening or 6 months before Screening (that is, answering "Yes" to questions 4 or 5 on the C-SSRS)
14. History of autoimmune disease or immunodeficiency
15. Known to be positive for tuberculosis test (T-spot. TB Test) at Screening
16. Received immunoglobulin or blood preparation within 6 months before the study treatment
17. Received inoculation within 4 weeks before the study treatment (8 weeks before in case of live or attenuated vaccine)
18. Family living together or cohabitant of a patient with an influenza virus infection
19. In contact with Coronavirus disease (COVID 19) patient within 4 weeks before study drug administration
20. Known to be other than negative for Severe acute respiratory syndrome coronavirus 2 (SARS Cov 2) antibody test at Screening
21. Known to be other than negative for SARS Cov 2 polymerase chain reaction (PCR) test at Screening or Baseline
22. History of retinopathy, maculopathy or macular degeneration

Primary outcomes:
measure: Incidence of Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to 28 days after the last dose of study drug (approximately Day 35)
measure: Cmax: Maximum Observed Plasma Concentration for E6742 and its Metabolite (ER-001132963) on Day 1
timeFrame: Day 1: 0-12 hours
measure: tmax: Time at Which the Highest Drug Plasma Concentration Occurs for E6742 and its Metabolite (ER-001132963) on Day 1
timeFrame: Day 1: 0-12 hours
measure: AUC(0-12h): Area Under the Plasma Concentration-time Curve From Zero Time to 12 Hours Postdose for E6742 and its Metabolite (ER-001132963) on Day 1
timeFrame: Day 1: 0-12 hours
measure: AUC Metabolite to E6742 Ratio Following Molecular Weight Correction to E6742 Equivalents on Day 1
timeFrame: Day 1: 0-12 hours
measure: Css,max: Maximum Observed Plasma Concentration at Steady State for E6742 and its Metabolite (ER-001132963) on Day 7
timeFrame: Day 7: 0-168 hours
measure: tss,max: Time at Which the Highest Drug Plasma Concentration Occurs at Steady State for E6742 and its Metabolite (ER-001132963) on Day 7
timeFrame: Day 7: 0-168 hours
measure: Css,av: Average Steady State Plasma Concentration for E6742 and its Metabolite (ER-001132963) on Day 7
timeFrame: Day 7: 0-168 hours
measure: AUC(0-t): Area Under the Plasma Concentration-time Curve From Zero Time to Time of Last Quantifiable Concentration for E6742 and its Metabolite (ER-001132963) on Day 7
timeFrame: Day 7: 0-168 hours
measure: AUC(0-12hr): Area Under the Plasma Concentration-time Curve Within a Dosing Interval at Steady State for E6742 and its Metabolite (ER-001132963) on Day 7
timeFrame: Day 7: 0-12 hours
measure: t1/2: Terminal Elimination Phase Half-life for E6742 and its Metabolite (ER-001132963) on Day 7
timeFrame: Day 7: 0-168 hours
measure: CLss/F: Apparent Total Clearance at Steady State for E6742 on Day 7
timeFrame: Day 7: 0-168 hours
measure: Vss/F: Apparent Volume of Distribution at Steady State for E6742 on Day 7
timeFrame: Day 7: 0-168 hours
measure: PTF: Peak-trough Fluctuation for E6742 and its Metabolite (ER-001132963) on Day 7
timeFrame: Day 7: 0-168 hours
measure: Accumulation Ratio for Cmax and AUC for E6742 and its Metabolite (ER-001132963) on Day 7
timeFrame: Day 7: 0-168 hours
measure: Metabolite to E6742 AUC Ratio Following Molecular Weight Correction to E6742 Equivalents on Day 7
timeFrame: Day 7: 0-168 hours
measure: AUC(0-12hr)ss: Area Under the Plasma Concentration-time Curve Within a Dosing Interval at Steady State for E6742 and its Metabolite (ER-001132963) on Day 7
timeFrame: Day 7: 0-12 hours
Secondary outcomes:
measure: Change From Baseline in Corrected QT Interval (QTc) for E6742
timeFrame: Day 1 and 7: 0-12 hours
Other outcomes:
Locations:
city: Bunkyō-Ku
country: Japan
facility: Eisai Trial Site #1
state: Tokyo
Study officials:
References: