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

EA Pharma

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteers

Treatments: Drug: EA1080; Drug: EA1080-matching placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04223960

2019-001886-34 (EudraCT Number)

EA1080-CP1

Details and patient eligibility

About

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.

Full 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

Enrollment: 184 patients

Sex: Male

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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184 participants in 26 patient groups

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

Experimental group

Description:

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).

Treatment:

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080-matching placebo

Drug: EA1080

Drug: EA1080

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

Experimental group

Description:

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).

Treatment:

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080-matching placebo

Drug: EA1080

Drug: EA1080

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

Experimental group

Description:

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).

Treatment:

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080-matching placebo

Drug: EA1080

Drug: EA1080

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

Experimental group

Description:

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).

Treatment:

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080-matching placebo

Drug: EA1080

Drug: EA1080

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

Experimental group

Description:

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.

Treatment:

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080-matching placebo

Drug: EA1080

Drug: EA1080

Part A: FE and Optional BA in Healthy Caucasian Participants

Experimental group

Description:

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.

Treatment:

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080

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

Experimental group

Description:

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.

Treatment:

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080

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

Experimental group

Description:

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).

Treatment:

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080-matching placebo

Drug: EA1080

Drug: EA1080

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

Experimental group

Description:

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).

Treatment:

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080-matching placebo

Drug: EA1080

Drug: EA1080

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

Experimental group

Description:

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).

Treatment:

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080-matching placebo

Drug: EA1080

Drug: EA1080

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

Experimental group

Description:

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).

Treatment:

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080-matching placebo

Drug: EA1080

Drug: EA1080

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

Experimental group

Description:

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.

Treatment:

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080-matching placebo

Drug: EA1080

Drug: EA1080

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

Experimental group

Description:

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).

Treatment:

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080-matching placebo

Drug: EA1080

Drug: EA1080

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

Experimental group

Description:

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).

Treatment:

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080-matching placebo

Drug: EA1080

Drug: EA1080

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

Experimental group

Description:

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).

Treatment:

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080-matching placebo

Drug: EA1080

Drug: EA1080

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

Experimental group

Description:

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).

Treatment:

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080-matching placebo

Drug: EA1080

Drug: EA1080

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

Experimental group

Description:

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.

Treatment:

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080-matching placebo

Drug: EA1080

Drug: EA1080

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

Experimental group

Description:

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.

Treatment:

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080-matching placebo

Drug: EA1080

Drug: EA1080

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

Experimental group

Description:

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.

Treatment:

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080-matching placebo

Drug: EA1080

Drug: EA1080

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

Experimental group

Description:

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.

Treatment:

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080-matching placebo

Drug: EA1080

Drug: EA1080

Part B: FE/BA, in Healthy Caucasian Participants

Experimental group

Description:

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.

Treatment:

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080

Part B: FE/BA, in Healthy Japanese Participants

Experimental group

Description:

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.

Treatment:

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080

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

Experimental group

Description:

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).

Treatment:

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080-matching placebo

Drug: EA1080

Drug: EA1080

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

Experimental group

Description:

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).

Treatment:

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080-matching placebo

Drug: EA1080

Drug: EA1080

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

Experimental group

Description:

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).

Treatment:

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080-matching placebo

Drug: EA1080

Drug: EA1080

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

Experimental group

Description:

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).

Treatment:

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080

Drug: EA1080-matching placebo

Drug: EA1080

Drug: EA1080