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

NCT04223960 | Completed Phase 1

• 2 other identifiers: EA1080-CP12019-001886-34
• Study Type: interventional
• Target: 184
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy Volunteers

Keywords

EA1080; Pharmacokinetics; Food effect study; Pharmacodynamics

Outcome Measures

Primary Outcomes (4)

• Parts A and B: Number of Participants With Treatment-emergent Adverse Events (TEAEs)

  Up to approximately 3 year 4 months

• Parts A and B: Percentage of Participants With Clinically Significant Change From Baseline in Laboratory Parameter Values

  Up to approximately 3 year 4 months

• 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

• 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 Outcomes (20)

• 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

• 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

• 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

• 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

• 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

Study Arms (26)

Part A: SAD, EA1080 Formulation A in Healthy Caucasian Participants

EXPERIMENTAL

Healthy Caucasian participants will receive EA1080 Formulation A or matching placebo orally, once on Day 1 of SAD part of the study. In SAD, there will be a maximum of 7 dose levels (three-four planned cohorts and three optional cohorts).

Drug: EA1080; Drug: EA1080-matching placebo

Part A: SAD, EA1080 Formulation B in Healthy Caucasian Participants

EXPERIMENTAL

Healthy Caucasian participants will receive EA1080 Formulation B or matching placebo orally, once on Day 1 of SAD part of the study. In SAD, there will be a maximum of 7 dose levels (three-four planned cohorts and three optional cohorts).

Drug: EA1080; Drug: EA1080-matching placebo

Part A: SAD, EA1080 Formulation C in Healthy Caucasian Participants

EXPERIMENTAL

Healthy Caucasian participants will receive EA1080 Formulation C or matching placebo orally, once on Day 1 of SAD part of the study. In SAD, there will be a maximum of 7 dose levels (three-four planned cohorts and three optional cohorts).

Drug: EA1080; Drug: EA1080-matching placebo

Part A: SAD, EA1080 Formulation D in Healthy Caucasian Participants

EXPERIMENTAL

Healthy Caucasian participants will receive EA1080 Formulation D or matching placebo orally, once on Day 1 of SAD part of the study. In SAD, there will be a maximum of 7 dose levels (three-four planned cohorts and three optional cohorts).

Drug: EA1080; Drug: EA1080-matching placebo

Part A: SAD, EA1080 in Healthy Japanese Participants (Optional)

EXPERIMENTAL

Healthy Japanese participants will receive any EA1080 formulation (Formulation A, Formulation B, Formulation C, and Formulation D) or matching placebo orally, once on Day 1 of SAD part of the study. There will be a maximum of six dose levels (three planned and three optional cohorts) per formulation.

Drug: EA1080; Drug: EA1080-matching placebo

Part A: FE and Optional BA in Healthy Caucasian Participants

EXPERIMENTAL

Healthy Caucasian participants will receive EA1080 on Day 1 and Day 8 in selected formulations (Formulation A, Formulation B, Formulation C, and Formulation D) in fed and fasted states. These formulations may be tested in any order or combination up to eight- way crossover design. The order will be dependent on the treatment sequence in which participants will be allocated to treatment. A washout period of 7 days will be maintained between the dosing days of each treatment periods.

Drug: EA1080

Part A: FE and Optional BA, in Healthy Japanese Participants

EXPERIMENTAL

Healthy Japanese participants will receive EA1080 on Day 1 and Day 8 in selected formulations (Formulation A, Formulation B, Formulation C, and Formulation D) in fed and fasted states. These formulations may be tested in any order or combination up to four-way crossover design. The order will be dependent on the treatment sequence in which participants will be allocated to treatment. A washout period of 7 days will be maintained between the dosing days of each treatment periods.

Drug: EA1080

Part A: MAD, EA1080 Formulation A in Healthy Caucasian Participants

EXPERIMENTAL

Healthy Caucasian participants will receive EA1080 Formulation A or matching placebo orally, once on Day 1 then multiple daily doses beginning on Day 8 up to Day 21 in MAD part of the study. In MAD, there will be a maximum of 6 dose levels (three planned cohorts and three optional cohorts).

Drug: EA1080; Drug: EA1080-matching placebo

Part A: MAD, EA1080 Formulation B in Healthy Caucasian Participants

EXPERIMENTAL

Healthy Caucasian participants will receive EA1080 Formulation B or matching placebo orally, once on Day 1 then multiple daily doses beginning on Day 8 up to Day 21 in MAD part of the study. In MAD, there will be a maximum of 6 dose levels (three planned cohorts and three optional cohorts).

Drug: EA1080; Drug: EA1080-matching placebo

Part A: MAD, EA1080 Formulation C in Healthy Caucasian Participants

EXPERIMENTAL

Healthy Caucasian participants will receive EA1080 Formulation C or matching placebo orally, once on Day 1 then multiple daily doses beginning on Day 8 up to Day 21 in MAD part of the study. In MAD, there will be a maximum of 6 dose levels (three planned cohorts and three optional cohorts).

Drug: EA1080; Drug: EA1080-matching placebo

Part A: MAD, EA1080 Formulation D in Healthy Caucasian Participants

EXPERIMENTAL

Healthy Caucasian participants will receive EA1080 Formulation D or matching placebo orally, once on Day 1 then multiple daily doses beginning on Day 8 up to Day 21 in MAD part of the study. In MAD, there will be a maximum of 6 dose levels (three planned dose level and three optional).

Drug: EA1080; Drug: EA1080-matching placebo

Part A: MAD, EA1080 in Healthy Japanese Participants (Optional)

EXPERIMENTAL

Healthy Japanese participants will receive any EA1080 formulation (Formulation A, Formulation B, Formulation C, and Formulation D) or matching placebo orally, once on Day 1 then multiple daily doses beginning on Day 8 up to Day 21 in MAD part of the study. In MAD, there will be a maximum of 6 dose levels (three planned dose level and three optional) per formulation.

Drug: EA1080; Drug: EA1080-matching placebo

Part B: SAD, EA1080 Formulation E in Healthy Caucasian Participants

EXPERIMENTAL

Healthy Caucasian participants will receive EA1080 Formulation E or matching placebo orally, once on Day 1 of SAD part of the study (three planned cohorts and six optional cohorts).

Drug: EA1080-matching placebo; Drug: EA1080

Part B: SAD, EA1080 Formulation E in Healthy Japanese Participants

EXPERIMENTAL

Healthy Japanese participants will receive EA1080 Formulation E or matching placebo orally, once on Day 1 of SAD part of the study (three planned cohorts and six optional cohorts).

Drug: EA1080-matching placebo; Drug: EA1080

Part B: SAD, EA1080 Formulation F in Healthy Caucasian Participants

EXPERIMENTAL

Healthy Caucasian participants will receive EA1080 Formulation F or matching placebo orally, once on Day 1 of SAD part of the study (three planned cohorts and six optional cohorts).

Drug: EA1080-matching placebo; Drug: EA1080

Part B: SAD, EA1080 Formulation F in Healthy Japanese Participants

EXPERIMENTAL

Healthy Japanese participants will receive EA1080 Formulation E or matching placebo orally, once on Day 1 of SAD part of the study (three planned cohorts and six optional cohorts).

Drug: EA1080-matching placebo; Drug: EA1080

Part B: SAD-FE, EA1080 Formulation E in Healthy Caucasian Participants

EXPERIMENTAL

Healthy Caucasian participants will receive EA1080 Formulation E or matching placebo on Day 1 in fasted state followed by EA1080 Formulation E on Day 8 in fed states. A washout period of 6 days will be maintained between the dosing days.

Drug: EA1080-matching placebo; Drug: EA1080

Part B: SAD-FE, EA1080 Formulation E in Healthy Japanese Participants

EXPERIMENTAL

Healthy Japanese participants will receive EA1080 Formulation E or matching placebo on Day 1 in fasted state followed by EA1080 Formulation E on Day 8 in fed states. A washout period of 6 days will be maintained between the dosing days.

Drug: EA1080-matching placebo; Drug: EA1080

Part B: SAD-FE, EA1080 Formulation F in Healthy Caucasian Participants

EXPERIMENTAL

Healthy Caucasian participants will receive EA1080 Formulation F or matching placebo on Day 1 in fasted state followed by EA1080 Formulation F on Day 8 in fed states. A washout period of 6 days will be maintained between the dosing days.

Drug: EA1080-matching placebo; Drug: EA1080

Part B: SAD-FE, EA1080 Formulation F in Healthy Japanese Participants

EXPERIMENTAL

Healthy Japanese participants will receive EA1080 Formulation F or matching placebo on Day 1 in fasted state followed by EA1080 Formulation F on Day 8 in fed states. A washout period of 6 days will be maintained between the dosing days.

Drug: EA1080-matching placebo; Drug: EA1080

Part B: FE/BA, in Healthy Caucasian Participants

EXPERIMENTAL

Healthy Caucasian participants will receive EA1080 on Days 1 8 and 15 in selected formulations (Formulation E in fasted state, Formulation F in fasted state, Formulation F in fed state). These formulations will be tested in a crossover design. The order will be dependent on the treatment sequence in which participants will be allocated to treatment. A washout period of 6 days will be maintained between the dosing days of each treatment periods.

Drug: EA1080

Part B: FE/BA, in Healthy Japanese Participants

EXPERIMENTAL

Healthy Japanese participants will receive EA1080 on Days 1 8 and 15 in selected formulations (Formulation E in fasted state, Formulation F in fasted state, Formulation F in fed state). These formulations will be tested in a crossover design. The order will be dependent on the treatment sequence in which participants will be allocated to treatment. A washout period of 6 days will be maintained between the dosing days of each treatment periods.

Drug: EA1080

Part B: MAD, EA1080 Formulation E in Healthy Caucasian Participants

EXPERIMENTAL

Healthy Caucasian participants will receive EA1080 Formulation E or matching placebo orally, once on Day 1 then multiple daily doses beginning on Day 8 up to Day 17 in Part B, MAD of the study. In Part B, MAD, there will be a maximum of 6 dose levels (one-three planned dose level and six optional).

Drug: EA1080-matching placebo; Drug: EA1080

Part B: MAD, EA1080 Formulation E in Healthy Japanese Participants

EXPERIMENTAL

Healthy Japanese participants will receive EA1080 Formulation E or matching placebo orally, once on Day 1 then multiple daily doses beginning on Day 8 up to Day 17 in Part B, MAD of the study. In Part B, MAD, there will be a maximum of 6 dose levels (one-three planned dose level and six optional).

Drug: EA1080-matching placebo; Drug: EA1080

Part B: MAD, EA1080 Formulation F in Healthy Caucasian Participants

EXPERIMENTAL

Healthy Caucasian participants will receive EA1080 Formulation F or matching placebo orally, once on Day 1 then multiple daily doses beginning on Day 8 up to Day 17 in Part B, MAD of the study. In Part B, MAD, there will be a maximum of 6 dose levels (one-three planned dose level and six optional).

Drug: EA1080-matching placebo; Drug: EA1080

Part B: MAD, EA1080 Formulation F in Healthy Japanese Participants

EXPERIMENTAL

Healthy Japanese participants will receive EA1080 Formulation F or matching placebo orally, once on Day 1 then multiple daily doses beginning on Day 8 up to Day 17 in Part B, MAD of the study. In Part B, MAD, there will be a maximum of 6 dose levels (one-three planned dose level and six optional).

Drug: EA1080-matching placebo; Drug: EA1080

Interventions

EA1080 DRUG

EA1080 Formulation A.

Part A: FE and Optional BA in Healthy Caucasian Participants; Part A: FE and Optional BA, in Healthy Japanese Participants; Part A: MAD, EA1080 Formulation A in Healthy Caucasian Participants; Part A: MAD, EA1080 in Healthy Japanese Participants (Optional); Part A: SAD, EA1080 Formulation A in Healthy Caucasian Participants; Part A: SAD, EA1080 in Healthy Japanese Participants (Optional)

EA1080-matching placebo DRUG

EA1080-matching placebo.

Part A: MAD, EA1080 Formulation A in Healthy Caucasian Participants; Part A: MAD, EA1080 Formulation B in Healthy Caucasian Participants; Part A: MAD, EA1080 Formulation C in Healthy Caucasian Participants; Part A: MAD, EA1080 Formulation D in Healthy Caucasian Participants; Part A: MAD, EA1080 in Healthy Japanese Participants (Optional); Part A: SAD, EA1080 Formulation A in Healthy Caucasian Participants; Part A: SAD, EA1080 Formulation B in Healthy Caucasian Participants; Part A: SAD, EA1080 Formulation C in Healthy Caucasian Participants; Part A: SAD, EA1080 Formulation D in Healthy Caucasian Participants; Part A: SAD, EA1080 in Healthy Japanese Participants (Optional); Part B: MAD, EA1080 Formulation E in Healthy Caucasian Participants; Part B: MAD, EA1080 Formulation E in Healthy Japanese Participants; Part B: MAD, EA1080 Formulation F in Healthy Caucasian Participants; Part B: MAD, EA1080 Formulation F in Healthy Japanese Participants; Part B: SAD, EA1080 Formulation E in Healthy Caucasian Participants; Part B: SAD, EA1080 Formulation E in Healthy Japanese Participants; Part B: SAD, EA1080 Formulation F in Healthy Caucasian Participants; Part B: SAD, EA1080 Formulation F in Healthy Japanese Participants; Part B: SAD-FE, EA1080 Formulation E in Healthy Caucasian Participants; Part B: SAD-FE, EA1080 Formulation E in Healthy Japanese Participants; Part B: SAD-FE, EA1080 Formulation F in Healthy Caucasian Participants; Part B: SAD-FE, EA1080 Formulation F in Healthy Japanese Participants

Eligibility Criteria

• Age: 18 Years - 45 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participants must meet all of the following criteria to be eligible for enrolment in this study:
• 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
• Participants in Japanese cohorts must be healthy males, aged \>=20 to \<=45 years at the date of signing informed consent
• 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.

You may not qualify if:

• Participants will be excluded from enrolment in this study if they meet any of the following criteria:
• Positive test for Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at screening
• Consumption of herbal remedies or dietary supplements containing St. John's Wort 30 days before the first day of dosing
• Has donated or lost 400 milliliter (mL) blood or more within the last 16 weeks preceding the first day of dosing
• An inability to follow a standardised diet and meal schedule or inability to fast, as required during the study
• 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
• 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)
• 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
• An absolute lymphocyte count below 0.9\*10\^9 per liter (/L) at screening or on Day -1
• Participants in receipt of any vaccination for Corona virus disease (COVID-19) within 14 days prior to the first dose administration.
• 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.
• Unwillingness to receive COVID-19 testing per local or site COVID-19 guidance.

Sponsors & Collaborators

• EA Pharma Co., Ltd.: lead

Study Sites (1)

Richmond Pharmacology Ltd

London, United Kingdom

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: January 2, 2020
• First Posted: January 13, 2020
• Study Start: January 9, 2020
• Primary Completion: August 6, 2023
• Study Completion: August 6, 2023
• Last Updated: December 26, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)