A Study to Assess the Safety and Tolerability of E6742 in Japanese Healthy Adult Participants

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04683185
• Other study ID #: E6742-J081-005
• Secondary ID: jRCT2031200316
• Status: Completed
• Phase: Phase 1
• Start date: December 28, 2020
• Est. completion date: June 21, 2021

Study information

• Verified date: May 2021
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: June 21, 2021
• Est. primary completion date: June 21, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• E6742
E6742 tablets.
• Placebo
E6742-matched placebo tablets.

Locations

Country	Name	City	State
Japan	Eisai Trial Site #1	Bunkyo-Ku	Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Co., Ltd.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	Safety assessments will consist of monitoring and recording all adverse events (AEs) and SAEs; laboratory evaluation for hematology, blood chemistry, and urine values; periodic measurement of vital signs and electrocardiograms (ECGs); and the performance of physical examinations.	Baseline up to 28 days after the last dose of study drug (approximately Day 35)
Primary	Cmax: Maximum Observed Plasma Concentration for E6742 and its Metabolite (ER-001132963) on Day 1		Day 1: 0-12 hours
Primary	tmax: Time at Which the Highest Drug Plasma Concentration Occurs for E6742 and its Metabolite (ER-001132963) on Day 1		Day 1: 0-12 hours
Primary	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		Day 1: 0-12 hours
Primary	AUC Metabolite to E6742 Ratio Following Molecular Weight Correction to E6742 Equivalents on Day 1		Day 1: 0-12 hours
Primary	Css,max: Maximum Observed Plasma Concentration at Steady State for E6742 and its Metabolite (ER-001132963) on Day 7		Day 7: 0-168 hours
Primary	tss,max: Time at Which the Highest Drug Plasma Concentration Occurs at Steady State for E6742 and its Metabolite (ER-001132963) on Day 7		Day 7: 0-168 hours
Primary	Css,av: Average Steady State Plasma Concentration for E6742 and its Metabolite (ER-001132963) on Day 7		Day 7: 0-168 hours
Primary	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		Day 7: 0-168 hours
Primary	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		Day 7: 0-12 hours
Primary	t1/2: Terminal Elimination Phase Half-life for E6742 and its Metabolite (ER-001132963) on Day 7		Day 7: 0-168 hours
Primary	CLss/F: Apparent Total Clearance at Steady State for E6742 on Day 7		Day 7: 0-168 hours
Primary	Vss/F: Apparent Volume of Distribution at Steady State for E6742 on Day 7		Day 7: 0-168 hours
Primary	PTF: Peak-trough Fluctuation for E6742 and its Metabolite (ER-001132963) on Day 7		Day 7: 0-168 hours
Primary	Accumulation Ratio for Cmax and AUC for E6742 and its Metabolite (ER-001132963) on Day 7		Day 7: 0-168 hours
Primary	Metabolite to E6742 AUC Ratio Following Molecular Weight Correction to E6742 Equivalents on Day 7		Day 7: 0-168 hours
Primary	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		Day 7: 0-12 hours
Secondary	Change From Baseline in Corrected QT Interval (QTc) for E6742	High precision method QT analysis (HPQT) will be performed using data extracted from the 12-hour holter recording obtained from the morning of day 1 (predose) through 12 hours after dosing, the morning of day 7 (predose) through 12 hours after dosing.	Day 1 and 7: 0-12 hours

External Links

•   Study results will be disclosed on the jRCT registry record.