A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Bioavailability, and Food-effects of EA1080 in Healthy Caucasian and Japanese Male Participants

Healthy Volunteers Clinical Trial

Official title:

A First-in-human, Randomized, Double-blinded, Placebo-controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Bioavailability and Food-effects of EA1080 in Healthy Caucasian and Japanese Male Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04223960
• Other study ID #: EA1080-CP1
• Secondary ID: 2019-001886-34
• Status: Completed
• Phase: Phase 1
• Start date: January 9, 2020
• Est. completion date: August 6, 2023

Study information

• Verified date: July 2023
• 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 and tolerability of EA1080 following single and multiple ascending oral doses in healthy Caucasian and Japanese male participants.

Description:

The drug being tested in this study is called EA1080. EA1080 is being tested to find a safe and well-tolerated dose in healthy Caucasian and Japanese male participants. The study consists of 2 parts as mentioned below:

Part A: This part of the study is fully adaptive and will be performed in three sub-parts as follows:

• Single ascending dose (SAD)

• Food Effect (FE) and optional bioavailability

• Multiple ascending dose (MAD)

Part B: This part of study is comprised of four sub-parts to assess Formulation E and Formulation F as follows:

• SAD

• An additional FE period in SAD cohorts (SAD-FE)

• Food Effect and bioavailability (FE/BA)

• MAD

Recruitment information / eligibility

• Status: Completed
• Enrollment: 184
• Est. completion date: August 6, 2023
• Est. primary completion date: August 6, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

Participants must meet all of the following criteria to be eligible for enrolment in this study:

1. Participants in Caucasian cohorts must be healthy males, aged greater than or equal (>=) 18 to less than or equal to (<=) 45 years at the date of signing informed consent

2. Participants in Japanese cohorts must be healthy males, aged >=20 to <=45 years at the date of signing informed consent

3. Participants must have a body mass index (BMI) between 18.5-25.0 kilogram per square meter (kg/m^2) inclusive at screening, Day -3, Day -2 or Day -1.

Exclusion Criteria:

Participants will be excluded from enrolment in this study if they meet any of the following criteria:

1. Positive test for Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at screening

2. Consumption of herbal remedies or dietary supplements containing St. John's Wort 30 days before the first day of dosing

3. Has donated or lost 400 milliliter (mL) blood or more within the last 16 weeks preceding the first day of dosing

4. An inability to follow a standardised diet and meal schedule or inability to fast, as required during the study

5. Prior screen failure (where the cause of the screen failure is not deemed to be temporary), randomisation, participation, or enrolment in this study. Participants who initially failed due to temporary non-medically significant issues are eligible for re-screening once the cause has resolved

6. Participants with veins on either arm that are unsuitable for intravenous puncture or cannulation (example, veins that are difficult to locate, or a tendency to rupture during puncture)

7. Participants with any medical condition which may cause raised intracranial pressure, participants with new or changing headaches, and participants with history of head or spinal trauma

8. An absolute lymphocyte count below 0.9*10^9 per liter (/L) at screening or on Day -1

9. Participants in receipt of any vaccination for Corona virus disease (COVID-19) within 14 days prior to the first dose administration.

10. History of COVID-19 polymerase chain reaction (PCR) positivity within 3 months of Day 1, suspected COVID-19 based on clinical presentation within 3 months of Day 1, or presence of clinically relevant long term sequelae of COVID-19.

11. Unwillingness to receive COVID-19 testing per local or site COVID-19 guidance.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• EA1080
EA1080 Formulation A.
• EA1080
EA1080 Formulation B.
• EA1080
EA1080 Formulation C.
• EA1080
EA1080 Formulation D.
• EA1080-matching placebo
EA1080-matching placebo.
• EA1080
EA1080 Formulation E.
• EA1080
EA1080 Formulation F.

Locations

Country	Name	City	State
United Kingdom	Richmond Pharmacology Ltd	London

Sponsors (1)

Lead Sponsor	Collaborator
EA Pharma Co., Ltd.

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Parts A and B: Number of Participants With Treatment-emergent Adverse Events (TEAEs)		Up to approximately 3 year 4 months
Primary	Parts A and B: Percentage of Participants With Clinically Significant Change From Baseline in Laboratory Parameter Values		Up to approximately 3 year 4 months
Primary	Parts A and B: Percentage of Participants With Abnormal, Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings		Up to approximately 3 year 4 months
Primary	Parts A and B: Percentage of Participants With Clinically Significant Change From Baseline in Vital Sign Values		Up to approximately 3 year 4 months
Secondary	Parts A and B: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of EA1080 and its Metabolite		Part A and B, SAD: Pre-dose (Day 1) and up to Day 8; Part A, FE and Part B, SAD and additional FE: Pre-dose (Day 1) and up to Day 15; Part B, FE/BA: Pre-dose (Day 1) and up to Day 22; MAD: Pre-dose (Day 1) and up to Day 28 Part A and up to Day 24 Part B
Secondary	Parts A and B: T1/2: Terminal Half-life of EA1080 and its Metabolite		Part A and B, SAD: Pre-dose (Day 1) and up to Day 8; Part A, FE and Part B, SAD and additional FE: Pre-dose (Day 1) and up to Day 15; Part B, FE/BA: Pre-dose (Day 1) and up to Day 22; MAD: Pre-dose (Day 1) and up to Day 28 Part A and up to Day 24 Part B
Secondary	Parts A and B: Cmax: Maximum Observed Plasma Concentration of EA1080 and its Metabolite		Part A and B, SAD: Pre-dose (Day 1) and up to Day 8; Part A, FE and Part B, SAD and additional FE: Pre-dose (Day 1) and up to Day 15; Part B, FE/BA: Pre-dose (Day 1) and up to Day 22; MAD: Pre-dose (Day 1) and up to Day 28 Part A and up to Day 24 Part B
Secondary	Parts A and B: AUC (0-t): Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration of EA1080 and its Metabolite		Part A and B, SAD: Pre-dose (Day 1) and up to Day 8; Part A, FE and Part B, SAD and additional FE: Pre-dose (Day 1) and up to Day 15; Part B, FE/BA: Pre-dose (Day 1) and up to Day 22; MAD: Pre-dose (Day 1) and up to Day 28 Part A and up to Day 24 Part B
Secondary	Parts A and B: AUC (0-inf): Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinite Time of EA1080 and its Metabolite		Part A and B, SAD: Pre-dose (Day 1) and up to Day 8; Part A, FE and Part B, SAD and additional FE: Pre-dose (Day 1) and up to Day 15; Part B, FE/BA: Pre-dose (Day 1) and up to Day 22; MAD: Pre-dose (Day 1) and up to Day 28 Part A and up to Day 24 Part B
Secondary	Parts A and B: %AUCextrap: Percentage of AUC (0-inf) That is due to Extrapolation From tlast to Infinity of EA1080 and its Metabolite		SAD: Pre-dose (Day 1) and up to Day 8; FE and optional BA: Pre-dose (Day 1) and up to Day 15; MAD: Pre-dose (Day 1) and up to Day 28 Part A and up to Day 24 Part B
Secondary	Parts A and B: CL/F: Apparent Total Body Clearance of EA1080 and its Metabolite		Part A and B, SAD: Pre-dose (Day 1) and up to Day 8; Part A, FE and Part B, SAD and additional FE: Pre-dose (Day 1) and up to Day 15; Part B, FE/BA: Pre-dose (Day 1) and up to Day 22; MAD: Pre-dose (Day 1) and up to Day 28 Part A and up to Day 24 Part B
Secondary	Parts A and B: Vz/F: Apparent Volume of Distribution During the Terminal Phase of EA1080 and its Metabolite		Part A and B, SAD: Pre-dose (Day 1) and up to Day 8; Part A, FE and Part B, SAD and additional FE: Pre-dose (Day 1) and up to Day 15; Part B, FE/BA: Pre-dose (Day 1) and up to Day 22; MAD: Pre-dose (Day 1) and up to Day 28 Part A and up to Day 24 Part B
Secondary	Parts A and B: Ae: Amount of Drug EA1080 Excreted in Urine		Part A and B, SAD: Pre-dose (Day 1) and up to Day 5; Part B, SAD and additional FE: Pre-dose (Day 1) and up to Day 5; Part A and B, MAD: Pre-dose (Day 1) and up to Day 25 Part A and Day 21 for Part B
Secondary	Parts A and B: fe: Percentage of EA1080 and its Metabolite Dose Excreted in Urine		Part A and B, SAD: Pre-dose (Day 1) and up to Day 5; Part B, SAD and additional FE: Pre-dose (Day 1) and up to Day 5; MAD: Pre-dose (Day 1) and up to Day 25 Part A and Day 21 for Part B
Secondary	Parts A and B: CLR: Renal Clearance of EA1080 and its Metabolite		Part A and B, SAD: Pre-dose (Day 1) and up to Day 5; Part B, SAD and additional FE: Pre-dose (Day 1) and up to Day 5; MAD: Pre-dose (Day 1) and up to Day 25 Part A and Day 21 for Part B
Secondary	Parts A and B: AUC (0-t): Area Under the Plasma Concentration-time Curve From Time Zero to the Final Dosing Interval (t) of EA1080 and its Metabolite		MAD: Pre-dose (Day 1) and up to Day 28 Part A and up to Day 24 Part B
Secondary	Parts A and Part B: Ctrough: Measured Plasma Concentration at the end of Each Dosing Interval of EA1080 and its Metabolite		MAD: Pre-dose (Day 1) and up to Day 28 Part A and up to Day 24 Part B
Secondary	Parts A and Part B: Cmax: Maximum Plasma Concentration Over the Dosing Period of EA1080 and its Metabolite		MAD: Pre-dose (Day 1) and up to Day 28 Part A and up to Day 24 Part B
Secondary	Parts A and Part B: AR(AUC): Accumulation Ratio For AUC0-t of EA1080 and its Metabolite		MAD: Pre-dose (Day 1) and up to Day 28 Part A and up to Day 24 Part B
Secondary	Parts A and Part B: AR(Cmax): Accumulation Ratio For Cmax of EA1080 and its Metabolite		MAD: Pre-dose (Day 1) and up to Day 28 Part A and up to Day 24 Part B
Secondary	Parts A and Part B: AUC of EA1080 in Each Formulation		Part A and B, SAD: Pre-dose (Day 1) and up to Day 8; Part A, FE and Part B, SAD and additional FE: Pre-dose (Day 1) and up to Day 15; Part B, FE/BA: Pre-dose (Day 1) and up to Day 22; MAD: Pre-dose (Day 1) and up to Day 28 Part A and up to Day 24 Part B
Secondary	Parts A and Part B: Cmax of EA1080 in Each Formulation		Part A and B, SAD: Pre-dose (Day 1) and up to Day 8; Part A, FE and Part B, SAD and additional FE: Pre-dose (Day 1) and up to Day 15; Part B, FE/BA: Pre-dose (Day 1) and up to Day 22; MAD: Pre-dose (Day 1) and up to Day 28 Part A and up to Day 24 Part B
Secondary	Parts A and Part B: AUC of EA1080 in Fed and Fasted State		Part A, FE: Pre-dose (Day 1) and up to Day 15; Part B SAD and additional FE: Pre-dose (Day 1) and up to Day 15; Part B, FE/BA: Pre-dose (Day 1) and up to Day 22
Secondary	Parts A and Part B: Cmax of EA1080 in Fed and Fasted State		Part A, FE: Pre-dose (Day 1) and up to Day 15; Part B SAD and additional FE: Pre-dose (Day 1) and up to Day 15; Part B, FE/BA: Pre-dose (Day 1) and up to Day 22