A Study to Determine the Absolute Bioavailability and the Absorption, Metabolism, and Elimination Properties of Carbon-14 (14C)E7386 in Healthy Male Participants

NCT05607537 | Completed Phase 1

• 2 other identifiers: E7386-E044-0032022-000954-27
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The primary purpose of this study is to evaluate the absolute bioavailability of E7386 following a single oral dose of E7386 as a one 40 milligram (mg) immediate release (IR) tablet and concomitant intravenous (IV) microdose of (14C)E7386 (100 mcg \[microgram\]) solution for Part 1 and to determine the pharmacokinetic (PK) and excretion of E7386 following a single 40 mg powder in capsule (PIC) oral administration of (14C)E7386 for Part 2.

Conditions

Healthy Volunteers

Keywords

E7386

Outcome Measures

Primary Outcomes (32)

• Part 1, %F: Percent Absolute Oral Bioavailability for (14C)E7386 and E7386

  Pre-dose (0 hour) up to 96 hours post-dose

• Part 1, Cmax: Maximum Observed Plasma Concentration for Total Radioactivity, (14C)E7386 and E7386

  Pre-dose (0 hour) up to 96 hours post-dose

• Part 1, Tlag: Time Delay Between Drug Administration and the Onset of Absorption for Total Radioactivity, (14C)E7386 and E7386

  Pre-dose (0 hour) up to 96 hours post-dose

• Part 1, Tmax: Time to Reach Maximum Observed Plasma Concentration (Cmax) for Total Radioactivity, (14C)E7386 and E7386

  Pre-dose (0 hour) up to 96 hours post-dose

• Part 1, AUC(0-12h): Area Under the Plasma Concentration-time Curve From Time Zero to 12 hours Post-dose for Total Radioactivity, (14C)E7386 and E7386

  Pre-dose (0 hour) up to 12 hours post-dose

• Part 1, AUC(0-24h): Area Under the Plasma Concentration-time Curve From Time Zero to 24 hours Post-dose for Total Radioactivity, (14C)E7386 and E7386

  Pre-dose (0 hour) up to 24 hours post-dose

• Part 1, AUC(0-last): Area Under the Plasma Concentration-time Curve from Time 0 to Time of the Last Measurable Concentration for Total Radioactivity, (14C)E7386 and E7386

  Pre-dose (0 hour) up to 96 hours post-dose

• Part 1, AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time for Total Radioactivity, (14C)E7386 and E7386

  Pre-dose (0 hour) up to 96 hours post-dose

• Part 1, t1/2: Apparent Terminal Elimination Phase Half-life for Total Radioactivity, (14C)E7386 and E7386

  Pre-dose (0 hour) up to 96 hours post-dose

• Part 1, MRT: Mean Residence Time of (14C)E7386

  Pre-dose (0 hour) up to 96 hours post-dose

• Part 1, CL: Total Clearance of (14C)E7386

  Pre-dose (0 hour) up to 96 hours post-dose

• Part 1, CL/F: Apparent Total Body Clearance of E7386

  Pre-dose (0 hour) up to 96 hours post-dose

• Part 1, Vss: Volume of Distribution at Steady State of (14C)E7386

  Pre-dose (0 hour) up to 96 hours post-dose

• Part 1, Vz/F: Apparent Volume of Distribution at Terminal Phase of E7386

  Pre-dose (0 hour) up to 96 hours post-dose

• Part 1, Fa: Percentage of Absorbed Dose Using Total Radioactivity in Urine

  Pre-dose (0 hour) up to 96 hours post-dose

• Part 2, Cmax: Maximum Observed Concentration for Total Radioactivity and E7386

  Pre-dose (0 hour) up to 480 hours post-dose

• Part 2, Tlag: Time Delay Between Drug Administration and the Onset of Absorption for Total Radioactivity and E7386

  Pre-dose (0 hour) up to 480 hours post-dose

• Part 2, Tmax: Time to Reach Maximum Observed Concentration (Cmax) for Total Radioactivity and E7386

  Pre-dose (0 hour) up to 480 hours post-dose

• Part 2, AUC(0-12h): Area Under the Concentration-time Curve From Time Zero to 12 hours Post-dose for Total Radioactivity and E7386

  Pre-dose (0 hour) up to 12 hours post-dose

• Part 2, AUC(0-24h): Area Under the Concentration-time Curve From Time Zero to 24 hours Post-dose for Total Radioactivity and E7386

  Pre-dose (0 hour) up to 24 hours post-dose

• Part 2, AUC(0-last): Area Under the Concentration-time Curve from Time 0 to Time of the Last Measurable Concentration for Total Radioactivity and E7386

  Pre-dose (0 hour) up to 480 hours post-dose

• Part 2, AUC(0-inf): Area Under the Concentration-time Curve From Time Zero to Infinite Time for Total Radioactivity and E7386

  Pre-dose (0 hour) up to 480 hours post-dose

• Part 2, t1/2: Apparent Terminal Elimination Phase Half-life for Total Radioactivity and E7386

  Pre-dose (0 hour) up to 480 hours post-dose

• Part 2, CL/F: Apparent Total Body Clearance of E7386

  Pre-dose (0 hour) up to 480 hours post-dose

• Part 2, Vz/F: Apparent Volume of Distribution at Terminal Phase of E7386

  Pre-dose (0 hour) up to 480 hours post-dose

• Part 2, feu: Percentage of Administered Radioactive Dose Excreted in Urine for Total Radioactivity

  Day -1 (Baseline) up to Day 49

• Part 2, Cumulative feu(0-tlast): Cumulative Radioactive Dose Excreted in Urine From Time 0 to Time of the Last Measurable Concentration

  Day -1 (Baseline) up to Day 49

• Part 2, fef: Percentage of Total Radioactivity Recovered in Feces Relative to the Administered Radioactive Dose

  Day -1 (Baseline) up to Day 49

• Part 2, Cumulative fef(0-tlast): Cumulative Radioactive Dose Excreted in Feces From Time 0 to Time of the Last Measurable Concentration

  Day -1 (Baseline) up to Day 49

• Part 2, feu+ef: Percentage of Total Radioactivity Recovered in Combined Urine and Feces Relative to the Administered Radioactive Dose

  Day -1 (Baseline) up to Day 49

• Part 2, Cumulative feu+ef(0-tlast): Cumulative Radioactive Dose excreted in Combined Excreta (Urine and Feces) From Time Zero to Time of the Last Measurable Concentration

  Day -1 (Baseline) up to Day 49

• Part 2, Fa: Percentage of Absorbed Dose Using Total Radioactivity in Urine

  Day -1 (Baseline) up to Day 49

Secondary Outcomes (9)

• Part 2 (Metabolic Profile of E7386): Concentration of Metabolite of E7386 in Plasma, Urine, and Feces

  Day 1 up to Day 21

• Parts 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  Part 1: Up to Day 5; Part 2: Up to Day 49

• Parts 1 and 2: Number of Participants With Abnormal Laboratory Values

  Part 1: Up to Day 5; Part 2: Up to Day 49

• Parts 1 and 2: Number of Participants With Abnormal Vital Signs Values

  Part 1: Up to Day 5; Part 2: Up to Day 49

• Parts 1 and 2: Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Values

  Part 1: Up to Day 5; Part 2: Up to Day 49

Study Arms (2)

Part 1: E7386 40 mg Tablet + (14C)E7386

EXPERIMENTAL

Participants will be administered a single oral dose of E7386 40 mg tablet on Day 1 followed by an intravenous infusion containing a microdose solution of \[14C\]E7386 (100 mcg) with not more than (NMT) 7.4 kilobecquerel (kBq) (0.20 microcurie \[mcCi\]), starting approximately 25 minutes post oral dose administered as 5 milliliter (mL) over 5 minutes to coincide with the time at which the highest drug concentration occurs (tmax) for E7386 after an oral dose.

Drug: E7386 Tablet; Drug: (14C)E7386

Part 2: (14C)E7386 40 mg Capsule

EXPERIMENTAL

Participants will be administered a single oral dose of E7386 40 mg capsule radiolabeled with approximately 2.96 megabecquerel (MBq) (80 mcCi) (14C)E7386 (final dose to depend on the specific activity of \[14C\]E7386) in the morning on Day 1 after an overnight fasting.

Drug: (14C)E7386 Capsule

Interventions

E7386 Tablet DRUG

E7386 40 mg tablet.

Part 1: E7386 40 mg Tablet + (14C)E7386

(14C)E7386 Capsule DRUG

(14C)E7386 40 mg capsule.

Part 2: (14C)E7386 40 mg Capsule

(14C)E7386 DRUG

(14C)E7386 administered intravenously.

Part 1: E7386 40 mg Tablet + (14C)E7386

Eligibility Criteria

• Age: 30 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Non-smoking, healthy male, age greater than or equal to (\>=) 30 years and less than or equal to (\<=) 55 years old at the time of informed consent
• Body Mass Index (BMI) of greater than (\>) 18 to less than (\<) 30 kilogram per square meter (kg/m\^2) as measured at Screening
• Adequate organ function per blood work
• Participant must have regular bowel movements (that is, average stool production of \>=1 and \<=3 stools per day)
• Participant must agree to adhere to the contraception requirements

You may not qualify if:

• Have participated in any clinical research study involving nonradiolabeled investigational product within 90 days prior to Day -1 (Baseline) or involving radiolabeled investigational product within 12 months prior to Day -1 (Baseline)
• Participant has had exposure to significant diagnostic or therapeutic radiation (example, serial X-ray, computed tomography scan, barium meal) or current employment in a job requiring radiation exposure monitoring within 12 months prior to Day -1 (Baseline)
• Male participant with pregnant or breastfeeding partner
• Male participant who is unwilling to follow the contraception rules of the study for up to 92 days after last dose of the study drug
• Clinically significant illness that requires medical treatment within 8 weeks or a clinically significant infection that requires medical treatment within 4 weeks prior to dosing
• A prolonged QT/QTc interval (QTcF \[corrected QT interval by Fridericia\] \>450 millisecond \[ms\]) as confirmed by a repeated ECG at Screening or Baseline, or a history of risk factors for torsade de pointes (example, heart failure, hypokalemia, family history of long QT Syndrome), or the use of concomitant medications that prolonged the QT/QTc interval
• Known history of clinically significant drug, food allergies, or presently experiencing any seasonal or perennial allergy at Screening and Baseline (Day -1)
• Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCVAb) or human immunodeficiency virus (HIV) antibody at Screening
• History of recreational drug use, drug or alcohol dependency or abuse within the 2 years before Screening, or those who have a positive urine drug test or breath alcohol test at Screening or admission
• Participant who is, or is an immediate family member of, a study site or sponsor employee
• Participant does not have suitable veins for multiple venipunctures/cannulations as assessed by the investigator or delegate at Screening
• Receipt of blood products within 4 weeks prior to dosing, or donation of blood or plasma within the previous 3 months, or loss of greater than 400 mL of blood
• Any history of or concomitant medical condition that in the opinion of the investigator would compromise the participant's ability to safely complete the study at Screening and Day -1 (Baseline)
• Failure to satisfy the investigator of fitness to participate for any other reason

Sponsors & Collaborators

• Eisai Limited: lead

Study Sites (1)

Labcorp Clinical Research Unit

Leeds, LS11 9EH, United Kingdom

Location

MeSH Terms

Interventions

E-7386

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2022
• First Posted: November 7, 2022
• Study Start: October 17, 2022
• Primary Completion: August 31, 2023
• Study Completion: August 31, 2023
• Last Updated: September 21, 2023

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)