Clinical trial NCT05607537: A Study to Determine the Absolute Bioavailability and the Absorption, Metabolism, and Elimination Properties of Carbon-14 (14C)E7386 in Healthy Male Participants
Official title: An Open-Label, Single-Center, 2-Part, Parallel Study to Determine the Absolute Bioavailability and the Absorption, Metabolism, and Elimination Properties of [14C]E7386 in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: E7386
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2022-11-07
Enrollment: 15
Sex: MALE
Minimum age (years): 30
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: Inclusion Criteria:

1. 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
2. Body Mass Index (BMI) of greater than (\>) 18 to less than (\<) 30 kilogram per square meter (kg/m\^2) as measured at Screening
3. Adequate organ function per blood work
4. Participant must have regular bowel movements (that is, average stool production of \>=1 and \<=3 stools per day)
5. Participant must agree to adhere to the contraception requirements

Exclusion Criteria:

1. 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)
2. 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)
3. Male participant with pregnant or breastfeeding partner
4. 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
5. 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
6. 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
7. Known history of clinically significant drug, food allergies, or presently experiencing any seasonal or perennial allergy at Screening and Baseline (Day -1)
8. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCVAb) or human immunodeficiency virus (HIV) antibody at Screening
9. 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
10. Participant who is, or is an immediate family member of, a study site or sponsor employee
11. Participant does not have suitable veins for multiple venipunctures/cannulations as assessed by the investigator or delegate at Screening
12. 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
13. 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)
14. Failure to satisfy the investigator of fitness to participate for any other reason

Primary outcomes:
measure: Part 1, %F: Percent Absolute Oral Bioavailability for (14C)E7386 and E7386
timeFrame: Pre-dose (0 hour) up to 96 hours post-dose
measure: Part 1, Cmax: Maximum Observed Plasma Concentration for Total Radioactivity, (14C)E7386 and E7386
timeFrame: Pre-dose (0 hour) up to 96 hours post-dose
measure: Part 1, Tlag: Time Delay Between Drug Administration and the Onset of Absorption for Total Radioactivity, (14C)E7386 and E7386
timeFrame: Pre-dose (0 hour) up to 96 hours post-dose
measure: Part 1, Tmax: Time to Reach Maximum Observed Plasma Concentration (Cmax) for Total Radioactivity, (14C)E7386 and E7386
timeFrame: Pre-dose (0 hour) up to 96 hours post-dose
measure: 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
timeFrame: Pre-dose (0 hour) up to 12 hours post-dose
measure: 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
timeFrame: Pre-dose (0 hour) up to 24 hours post-dose
measure: 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
timeFrame: Pre-dose (0 hour) up to 96 hours post-dose
measure: 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
timeFrame: Pre-dose (0 hour) up to 96 hours post-dose
measure: Part 1, t1/2: Apparent Terminal Elimination Phase Half-life for Total Radioactivity, (14C)E7386 and E7386
timeFrame: Pre-dose (0 hour) up to 96 hours post-dose
measure: Part 1, MRT: Mean Residence Time of (14C)E7386
timeFrame: Pre-dose (0 hour) up to 96 hours post-dose
measure: Part 1, CL: Total Clearance of (14C)E7386
timeFrame: Pre-dose (0 hour) up to 96 hours post-dose
measure: Part 1, CL/F: Apparent Total Body Clearance of E7386
timeFrame: Pre-dose (0 hour) up to 96 hours post-dose
measure: Part 1, Vss: Volume of Distribution at Steady State of (14C)E7386
timeFrame: Pre-dose (0 hour) up to 96 hours post-dose
measure: Part 1, Vz/F: Apparent Volume of Distribution at Terminal Phase of E7386
timeFrame: Pre-dose (0 hour) up to 96 hours post-dose
measure: Part 1, Fa: Percentage of Absorbed Dose Using Total Radioactivity in Urine
timeFrame: Pre-dose (0 hour) up to 96 hours post-dose
measure: Part 2, Cmax: Maximum Observed Concentration for Total Radioactivity and E7386
timeFrame: Pre-dose (0 hour) up to 480 hours post-dose
measure: Part 2, Tlag: Time Delay Between Drug Administration and the Onset of Absorption for Total Radioactivity and E7386
timeFrame: Pre-dose (0 hour) up to 480 hours post-dose
measure: Part 2, Tmax: Time to Reach Maximum Observed Concentration (Cmax) for Total Radioactivity and E7386
timeFrame: Pre-dose (0 hour) up to 480 hours post-dose
measure: Part 2, AUC(0-12h): Area Under the Concentration-time Curve From Time Zero to 12 hours Post-dose for Total Radioactivity and E7386
timeFrame: Pre-dose (0 hour) up to 12 hours post-dose
measure: Part 2, AUC(0-24h): Area Under the Concentration-time Curve From Time Zero to 24 hours Post-dose for Total Radioactivity and E7386
timeFrame: Pre-dose (0 hour) up to 24 hours post-dose
measure: 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
timeFrame: Pre-dose (0 hour) up to 480 hours post-dose
measure: Part 2, AUC(0-inf): Area Under the Concentration-time Curve From Time Zero to Infinite Time for Total Radioactivity and E7386
timeFrame: Pre-dose (0 hour) up to 480 hours post-dose
measure: Part 2, t1/2: Apparent Terminal Elimination Phase Half-life for Total Radioactivity and E7386
timeFrame: Pre-dose (0 hour) up to 480 hours post-dose
measure: Part 2, CL/F: Apparent Total Body Clearance of E7386
timeFrame: Pre-dose (0 hour) up to 480 hours post-dose
measure: Part 2, Vz/F: Apparent Volume of Distribution at Terminal Phase of E7386
timeFrame: Pre-dose (0 hour) up to 480 hours post-dose
measure: Part 2, feu: Percentage of Administered Radioactive Dose Excreted in Urine for Total Radioactivity
timeFrame: Day -1 (Baseline) up to Day 49
measure: Part 2, Cumulative feu(0-tlast): Cumulative Radioactive Dose Excreted in Urine From Time 0 to Time of the Last Measurable Concentration
timeFrame: Day -1 (Baseline) up to Day 49
measure: Part 2, fef: Percentage of Total Radioactivity Recovered in Feces Relative to the Administered Radioactive Dose
timeFrame: Day -1 (Baseline) up to Day 49
measure: Part 2, Cumulative fef(0-tlast): Cumulative Radioactive Dose Excreted in Feces From Time 0 to Time of the Last Measurable Concentration
timeFrame: Day -1 (Baseline) up to Day 49
measure: Part 2, feu+ef: Percentage of Total Radioactivity Recovered in Combined Urine and Feces Relative to the Administered Radioactive Dose
timeFrame: Day -1 (Baseline) up to Day 49
measure: 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
timeFrame: Day -1 (Baseline) up to Day 49
measure: Part 2, Fa: Percentage of Absorbed Dose Using Total Radioactivity in Urine
timeFrame: Day -1 (Baseline) up to Day 49
Secondary outcomes:
measure: Part 2 (Metabolic Profile of E7386): Concentration of Metabolite of E7386 in Plasma, Urine, and Feces
timeFrame: Day 1 up to Day 21
measure: Parts 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Part 1: Up to Day 5; Part 2: Up to Day 49
measure: Parts 1 and 2: Number of Participants With Abnormal Laboratory Values
timeFrame: Part 1: Up to Day 5; Part 2: Up to Day 49
measure: Parts 1 and 2: Number of Participants With Abnormal Vital Signs Values
timeFrame: Part 1: Up to Day 5; Part 2: Up to Day 49
measure: Parts 1 and 2: Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Values
timeFrame: Part 1: Up to Day 5; Part 2: Up to Day 49
measure: Parts 1 and 2: Number of Participants With Abnormal Ophthalmic Examinations
timeFrame: Part 1: Up to Day 5; Part 2: Up to Day 49
measure: Parts 1 and 2: Number of Participants who will Receive Concomitant Medications
timeFrame: Part 1: Up to Day 5; Part 2: Up to Day 49
measure: Parts 1 and 2: Number of Participants With Abnormal Physical Examinations
timeFrame: Part 1: Up to Day 5; Part 2: Up to Day 49
measure: Parts 1 and 2: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-suicide Severity Rating Scale (C-SSRS)
timeFrame: Part 1: Up to Day 5; Part 2: Up to Day 49
Other outcomes:
Locations:
city: Leeds
country: United Kingdom
facility: Labcorp Clinical Research Unit
Study officials:
References: