Clinical trial NCT04223960: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Bioavailability, and Food-effects of EA1080 in Healthy Caucasian and Japanese Male Participants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: EA1080
Pharmacokinetics
Food effect study
Pharmacodynamics
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2020-01-13
Enrollment: 184
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
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 and tolerability of EA1080 following single and multiple ascending oral doses in healthy Caucasian and Japanese male participants.

Detailed 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

Eligibility criteria: 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.

Primary outcomes:
measure: Parts A and B: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to approximately 3 year 4 months
measure: Parts A and B: Percentage of Participants With Clinically Significant Change From Baseline in Laboratory Parameter Values
timeFrame: Up to approximately 3 year 4 months
measure: Parts A and B: Percentage of Participants With Abnormal, Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings
timeFrame: Up to approximately 3 year 4 months
measure: Parts A and B: Percentage of Participants With Clinically Significant Change From Baseline in Vital Sign Values
timeFrame: Up to approximately 3 year 4 months
Secondary outcomes:
measure: Parts A and B: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of EA1080 and its Metabolite
timeFrame: 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
measure: Parts A and B: T1/2: Terminal Half-life of EA1080 and its Metabolite
timeFrame: 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
measure: Parts A and B: Cmax: Maximum Observed Plasma Concentration of EA1080 and its Metabolite
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: Parts A and B: %AUCextrap: Percentage of AUC (0-inf) That is due to Extrapolation From tlast to Infinity of EA1080 and its Metabolite
timeFrame: 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
measure: Parts A and B: CL/F: Apparent Total Body Clearance of EA1080 and its Metabolite
timeFrame: 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
measure: Parts A and B: Vz/F: Apparent Volume of Distribution During the Terminal Phase of EA1080 and its Metabolite
timeFrame: 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
measure: Parts A and B: Ae: Amount of Drug EA1080 Excreted in Urine
timeFrame: 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
measure: Parts A and B: fe: Percentage of EA1080 and its Metabolite Dose Excreted in Urine
timeFrame: 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
measure: Parts A and B: CLR: Renal Clearance of EA1080 and its Metabolite
timeFrame: 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
measure: Parts A and B: AUC (0-τ): Area Under the Plasma Concentration-time Curve From Time Zero to the Final Dosing Interval (τ) of EA1080 and its Metabolite
timeFrame: MAD: Pre-dose (Day 1) and up to Day 28 Part A and up to Day 24 Part B
measure: Parts A and Part B: Ctrough: Measured Plasma Concentration at the end of Each Dosing Interval of EA1080 and its Metabolite
timeFrame: MAD: Pre-dose (Day 1) and up to Day 28 Part A and up to Day 24 Part B
measure: Parts A and Part B: Cmax: Maximum Plasma Concentration Over the Dosing Period of EA1080 and its Metabolite
timeFrame: MAD: Pre-dose (Day 1) and up to Day 28 Part A and up to Day 24 Part B
measure: Parts A and Part B: AR(AUC): Accumulation Ratio For AUC0-τ of EA1080 and its Metabolite
timeFrame: MAD: Pre-dose (Day 1) and up to Day 28 Part A and up to Day 24 Part B
measure: Parts A and Part B: AR(Cmax): Accumulation Ratio For Cmax of EA1080 and its Metabolite
timeFrame: MAD: Pre-dose (Day 1) and up to Day 28 Part A and up to Day 24 Part B
measure: Parts A and Part B: AUC of EA1080 in Each Formulation
timeFrame: 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
measure: Parts A and Part B: Cmax of EA1080 in Each Formulation
timeFrame: 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
measure: Parts A and Part B: AUC of EA1080 in Fed and Fasted State
timeFrame: 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
measure: Parts A and Part B: Cmax of EA1080 in Fed and Fasted State
timeFrame: 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
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Richmond Pharmacology Ltd
Study officials:
References: