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

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05607537
• Other study ID #: E7386-E044-003
• Secondary ID: 2022-000954-27
• Status: Completed
• Phase: Phase 1
• Start date: October 17, 2022
• Est. completion date: August 31, 2023

Study information

• Verified date: September 2022
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: August 31, 2023
• Est. primary completion date: August 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 30 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• E7386 Tablet
E7386 40 mg tablet.
• (14C)E7386 Capsule
(14C)E7386 40 mg capsule.
• (14C)E7386
(14C)E7386 administered intravenously.

Locations

Country	Name	City	State
United Kingdom	Labcorp Clinical Research Unit	Leeds

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Limited

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1, %F: Percent Absolute Oral Bioavailability for (14C)E7386 and E7386		Pre-dose (0 hour) up to 96 hours post-dose
Primary	Part 1, Cmax: Maximum Observed Plasma Concentration for Total Radioactivity, (14C)E7386 and E7386		Pre-dose (0 hour) up to 96 hours post-dose
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Part 1, MRT: Mean Residence Time of (14C)E7386		Pre-dose (0 hour) up to 96 hours post-dose
Primary	Part 1, CL: Total Clearance of (14C)E7386		Pre-dose (0 hour) up to 96 hours post-dose
Primary	Part 1, CL/F: Apparent Total Body Clearance of E7386		Pre-dose (0 hour) up to 96 hours post-dose
Primary	Part 1, Vss: Volume of Distribution at Steady State of (14C)E7386		Pre-dose (0 hour) up to 96 hours post-dose
Primary	Part 1, Vz/F: Apparent Volume of Distribution at Terminal Phase of E7386		Pre-dose (0 hour) up to 96 hours post-dose
Primary	Part 1, Fa: Percentage of Absorbed Dose Using Total Radioactivity in Urine		Pre-dose (0 hour) up to 96 hours post-dose
Primary	Part 2, Cmax: Maximum Observed Concentration for Total Radioactivity and E7386		Pre-dose (0 hour) up to 480 hours post-dose
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Part 2, CL/F: Apparent Total Body Clearance of E7386		Pre-dose (0 hour) up to 480 hours post-dose
Primary	Part 2, Vz/F: Apparent Volume of Distribution at Terminal Phase of E7386		Pre-dose (0 hour) up to 480 hours post-dose
Primary	Part 2, feu: Percentage of Administered Radioactive Dose Excreted in Urine for Total Radioactivity		Day -1 (Baseline) up to Day 49
Primary	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
Primary	Part 2, fef: Percentage of Total Radioactivity Recovered in Feces Relative to the Administered Radioactive Dose		Day -1 (Baseline) up to Day 49
Primary	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
Primary	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
Primary	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
Primary	Part 2, Fa: Percentage of Absorbed Dose Using Total Radioactivity in Urine		Day -1 (Baseline) up to Day 49
Secondary	Part 2 (Metabolic Profile of E7386): Concentration of Metabolite of E7386 in Plasma, Urine, and Feces	Blood, urine and feces samples will be collected and analyzed to estimate the concentration of metabolite of E7386 by liquid chromatography/multiple-stage mass spectroscopy method.	Day 1 up to Day 21
Secondary	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
Secondary	Parts 1 and 2: Number of Participants With Abnormal Laboratory Values	Laboratory assessment will include hematology, clinical chemistry, and urinalysis parameters.	Part 1: Up to Day 5; Part 2: Up to Day 49
Secondary	Parts 1 and 2: Number of Participants With Abnormal Vital Signs Values	Vital sign measurements will include systolic and diastolic blood pressure (BP), pulse rate, respiratory rate, body temperature.	Part 1: Up to Day 5; Part 2: Up to Day 49
Secondary	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
Secondary	Parts 1 and 2: Number of Participants With Abnormal Ophthalmic Examinations		Part 1: Up to Day 5; Part 2: Up to Day 49
Secondary	Parts 1 and 2: Number of Participants who will Receive Concomitant Medications		Part 1: Up to Day 5; Part 2: Up to Day 49
Secondary	Parts 1 and 2: Number of Participants With Abnormal Physical Examinations		Part 1: Up to Day 5; Part 2: Up to Day 49
Secondary	Parts 1 and 2: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-suicide Severity Rating Scale (C-SSRS)	The C-SSRS is an interview-based rating scale to systematically assess any suicidality, suicidal behavior, or suicidal ideation. Any suicidality is emergence of any suicidal ideation or suicidal behavior. Any suicidal behavior is indicated when response is "yes" for any these questions- actual attempt to suicide, engaged in non-suicidal self-injurious behavior, interrupted attempt, aborted attempt, preparatory acts. Any suicidal ideation is indicated when response is "yes" for any of these questions- wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent to suicide.	Part 1: Up to Day 5; Part 2: Up to Day 49