A Study to Determine the Absolute Bioavailability and the Absorption, Metabolism, and Elimination Properties of Carbon-14 (14C)E7386 in Healthy Male Participants
Phase 1
Completed
- Conditions
- Healthy Volunteers
- Interventions
- Drug: E7386 TabletDrug: (14C)E7386 CapsuleDrug: (14C)E7386
- Registration Number
- NCT05607537
- Lead Sponsor
- Eisai Limited
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 15
Inclusion Criteria
- 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
Exclusion Criteria
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1: E7386 40 mg Tablet + (14C)E7386 E7386 Tablet 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. Part 1: E7386 40 mg Tablet + (14C)E7386 (14C)E7386 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. Part 2: (14C)E7386 40 mg Capsule (14C)E7386 Capsule 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.
- Primary Outcome Measures
Name Time Method 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 2, Cmax: Maximum Observed Concentration for Total Radioactivity and E7386 Pre-dose (0 hour) up to 480 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, %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, Fa: Percentage of Absorbed Dose Using Total Radioactivity in Urine Pre-dose (0 hour) up to 96 hours post-dose 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, Fa: Percentage of Absorbed Dose Using Total Radioactivity in Urine Day -1 (Baseline) up to Day 49 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, 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, 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, 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, fef: Percentage of Total Radioactivity Recovered in Feces Relative to the Administered Radioactive Dose Day -1 (Baseline) up to Day 49 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, 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+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
- Secondary Outcome Measures
Name Time Method Parts 1 and 2: Number of Participants With Abnormal Laboratory Values Part 1: Up to Day 5; Part 2: Up to Day 49 Laboratory assessment will include hematology, clinical chemistry, and urinalysis parameters.
Parts 1 and 2: Number of Participants With Abnormal Vital Signs Values Part 1: Up to Day 5; Part 2: Up to Day 49 Vital sign measurements will include systolic and diastolic blood pressure (BP), pulse rate, respiratory rate, body temperature.
Parts 1 and 2: Number of Participants With Abnormal Physical Examinations Part 1: Up to Day 5; Part 2: Up to Day 49 Parts 1 and 2: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-suicide Severity Rating Scale (C-SSRS) Part 1: Up to Day 5; Part 2: Up to Day 49 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.
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 Part 2 (Metabolic Profile of E7386): Concentration of Metabolite of E7386 in Plasma, Urine, and Feces Day 1 up to Day 21 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.
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 Parts 1 and 2: Number of Participants With Abnormal Ophthalmic Examinations Part 1: Up to Day 5; Part 2: Up to Day 49 Parts 1 and 2: Number of Participants who will Receive Concomitant Medications Part 1: Up to Day 5; Part 2: Up to Day 49
Trial Locations
- Locations (1)
Labcorp Clinical Research Unit
🇬🇧Leeds, United Kingdom