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A Study to Determine the Metabolism and Elimination of [14C]E2027 in Healthy Male Participants

Primary Purpose

Dementias With Lewy Bodies

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
E2027
Sponsored by
Eisai Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Dementias With Lewy Bodies focused on measuring E2027, [14C]E2027, Dementia with Lewy bodies, Dementia

Eligibility Criteria

18 Years - 55 Years (Adult)MaleAccepts Healthy Volunteers

Inclusion Criteria:

Participants must meet all of the following criteria to be included in this study:

1. Body Mass Index (BMI) of 18 to 30 kilogram per square meter (kg/m^2) at Screening

Exclusion Criteria

Participants who meet any of the following criteria will be excluded from this study:

  1. Have participated in a [14C]-research study within the 6 months prior to Day -1
  2. Exposure to clinically significant radiation (greater than [>] 100 millisieverts) within 12 months prior to Day -1
  3. Clinically significant illness that required medical treatment within 8 weeks or a clinically significant infection that required medical treatment within 4 weeks before dosing
  4. Any history of abdominal surgery that may affect pharmacokinetic profiles of study drug (example, hepatectomy, nephrectomy, digestive organ resection but not cholecystectomy nor appendectomy) at Screening or Baseline
  5. Any other clinically abnormal symptom or organ impairment found by medical history, physical examinations, vital signs, ECG finding (including PR > 210 millisecond [msec], QRS > 110 msec), or laboratory test results that required medical treatment at Screening or Baseline
  6. A prolonged QT/QTc interval (QTcF > 450 msec) as demonstrated by ECGs at Screening or Baseline
  7. Systolic blood pressure > 130 millimetres of mercury (mmHg) or diastolic blood pressure > 85 mmHg at Screening or Baseline
  8. Heart rate less than (<) 45 beats per minute (beats/min) or >100 beats/min at Screening or Baseline
  9. Known history of clinically significant drug allergy at Screening or Baseline
  10. Known history of food allergies or presently experiencing significant seasonal or perennial allergy at Screening or Baseline
  11. Known to be human immunodeficiency virus (HIV) positive at Screening
  12. Active viral hepatitis (A, B, or C) as demonstrated by positive serology at Screening
  13. History of drug or alcohol dependency or abuse within the 2 years before Screening, or those who have a positive urine drug or alcohol test at Screening or Baseline
  14. Use of tobacco or nicotine-containing products within 4 weeks before dosing
  15. Currently enrolled in another clinical trial or used any investigational drug or device within 30 days (or 5 half-lives, whichever is longer) preceding informed consent
  16. Engagement in strenuous exercise within 2 weeks before dosing (example, marathon runners, weight lifters)
  17. Intake of caffeinated beverages or caffeinated food within 72 hours before dosing
  18. Intake of nutritional supplements, juice, and herbal preparations or other foods or beverages that may affect the various drug metabolizing enzymes and transporters (example, alcohol, grapefruit, grapefruit juice, grapefruit-containing beverages, apple or orange juice, vegetables from the mustard green family [example, kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, mustard], and charbroiled meats) within 1 week before dosing
  19. Intake of herbal preparations containing St. John's Wort within 4 weeks before dosing Intake of over-the-counter (OTC) medications within 14 days (or 5 half-lives, whichever is longer) before dosing unless the investigator and sponsor medical monitor consider that they do not compromise participant safety or study assessments
  20. Use of any prescription drugs within 4 weeks before dosing
  21. Use of illegal recreational drugs
  22. Receipt of blood products within 4 weeks, or donation of blood within 8 weeks, or donation of plasma within 1 week of dosing

Sites / Locations

  • Covance Clinical Research Unit Inc.

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

E2027

Arm Description

Participants will receive approximately 130 microcurie (μCi) of [14C]E2027 as a single 50 milligram (mg) (free base), capsule, orally on Day 1.

Outcomes

Primary Outcome Measures

Cumulative Percent of the Radiolabeled Dose of [14C]E2027 in Biological Matrices (Blood, Urine, Feces and Toilet Tissue)
Blood, urine, feces and toilet tissue samples will be collected at specific time points and will be analyzed for the amount of radiolabeled [14C]E2027.
Maximum Concentration (Cmax) of Radiolabeled [14C]E2027, Non-Radiolabeled E2027 and Metabolites in Biological Matrices
Time to Reach Maximum (Peak) Concentration (Tmax) of Radiolabeled [14C]E2027, Non-Radiolabeled E2027 and Metabolites in Biological Matrices
Area Under the Concentration-Time Curve From Time Zero to 24 hours (AUC(0-24h)) of Radiolabeled [14C]E2027, Non-Radiolabeled E2027 and Metabolites in Biological Matrices
Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration (AUC(0-t)) of Radiolabeled [14C]E2027, Non-Radiolabeled E2027 and Metabolites in Biological Matrices
Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC(0-inf)) of Radiolabeled [14C]E2027, Non-Radiolabeled E2027 and Metabolites in Biological Matrices
Terminal Elimination Half-life (t1/2) of Radiolabeled [14C]E2027, Non-Radiolabeled E2027 and Metabolites in Biological Matrices
Apparent Total Body Clearance (CL/F) of E2027 in Biological Matrices
Apparent Volume of Distribution (Vd/F) of E2027 in Biological Matrices
Percent of AUC(0-inf) of Metabolite to E2027 in Biological Matrices

Secondary Outcome Measures

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Number of Participants With Clinically Significant Abnormal Laboratory Values
Number of Participants With Clinically Significant Abnormal Vital Sign Values
Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Findings
Number of Participants With Clinically Significant Abnormal Physical Examination Findings

Full Information

First Posted
July 16, 2019
Last Updated
December 2, 2019
Sponsor
Eisai Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04023877
Brief Title
A Study to Determine the Metabolism and Elimination of [14C]E2027 in Healthy Male Participants
Official Title
An Open-Label, Single-Dose Study to Determine the Metabolism and Elimination of [14C]E2027 in Healthy Male Subjects
Study Type
Interventional

2. Study Status

Record Verification Date
July 2019
Overall Recruitment Status
Completed
Study Start Date
July 18, 2019 (Actual)
Primary Completion Date
October 11, 2019 (Actual)
Study Completion Date
October 11, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eisai Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The primary objective of the study is to achieve mass balance recovery of [14C]-radiolabel in urine and feces and to identify and quantify the main elimination pathways of E2027.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dementias With Lewy Bodies
Keywords
E2027, [14C]E2027, Dementia with Lewy bodies, Dementia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Actual)

8. Arms, Groups, and Interventions

Arm Title
E2027
Arm Type
Experimental
Arm Description
Participants will receive approximately 130 microcurie (μCi) of [14C]E2027 as a single 50 milligram (mg) (free base), capsule, orally on Day 1.
Intervention Type
Drug
Intervention Name(s)
E2027
Intervention Description
E2027 oral capsule.
Primary Outcome Measure Information:
Title
Cumulative Percent of the Radiolabeled Dose of [14C]E2027 in Biological Matrices (Blood, Urine, Feces and Toilet Tissue)
Description
Blood, urine, feces and toilet tissue samples will be collected at specific time points and will be analyzed for the amount of radiolabeled [14C]E2027.
Time Frame
Up to 56 days
Title
Maximum Concentration (Cmax) of Radiolabeled [14C]E2027, Non-Radiolabeled E2027 and Metabolites in Biological Matrices
Time Frame
Pre-dose up to Day 56 post-dose
Title
Time to Reach Maximum (Peak) Concentration (Tmax) of Radiolabeled [14C]E2027, Non-Radiolabeled E2027 and Metabolites in Biological Matrices
Time Frame
Pre-dose up to Day 56 post-dose
Title
Area Under the Concentration-Time Curve From Time Zero to 24 hours (AUC(0-24h)) of Radiolabeled [14C]E2027, Non-Radiolabeled E2027 and Metabolites in Biological Matrices
Time Frame
Pre-dose up to Day 56 post-dose
Title
Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration (AUC(0-t)) of Radiolabeled [14C]E2027, Non-Radiolabeled E2027 and Metabolites in Biological Matrices
Time Frame
Pre-dose up to Day 56 post-dose
Title
Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC(0-inf)) of Radiolabeled [14C]E2027, Non-Radiolabeled E2027 and Metabolites in Biological Matrices
Time Frame
Pre-dose up to Day 56 post-dose
Title
Terminal Elimination Half-life (t1/2) of Radiolabeled [14C]E2027, Non-Radiolabeled E2027 and Metabolites in Biological Matrices
Time Frame
Pre-dose up to Day 56 post-dose
Title
Apparent Total Body Clearance (CL/F) of E2027 in Biological Matrices
Time Frame
Pre-dose up to Day 56 post-dose
Title
Apparent Volume of Distribution (Vd/F) of E2027 in Biological Matrices
Time Frame
Pre-dose up to Day 28 post-dose
Title
Percent of AUC(0-inf) of Metabolite to E2027 in Biological Matrices
Time Frame
Pre-dose up to Day 28 post-dose
Secondary Outcome Measure Information:
Title
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame
Up to 56 days post-dose
Title
Number of Participants With Clinically Significant Abnormal Laboratory Values
Time Frame
Up to 56 days post-dose
Title
Number of Participants With Clinically Significant Abnormal Vital Sign Values
Time Frame
Up to 56 days post-dose
Title
Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Findings
Time Frame
Up to 56 days post-dose
Title
Number of Participants With Clinically Significant Abnormal Physical Examination Findings
Time Frame
Baseline, Up to 56 days post-dose

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Participants must meet all of the following criteria to be included in this study: 1. Body Mass Index (BMI) of 18 to 30 kilogram per square meter (kg/m^2) at Screening Exclusion Criteria Participants who meet any of the following criteria will be excluded from this study: Have participated in a [14C]-research study within the 6 months prior to Day -1 Exposure to clinically significant radiation (greater than [>] 100 millisieverts) within 12 months prior to Day -1 Clinically significant illness that required medical treatment within 8 weeks or a clinically significant infection that required medical treatment within 4 weeks before dosing Any history of abdominal surgery that may affect pharmacokinetic profiles of study drug (example, hepatectomy, nephrectomy, digestive organ resection but not cholecystectomy nor appendectomy) at Screening or Baseline Any other clinically abnormal symptom or organ impairment found by medical history, physical examinations, vital signs, ECG finding (including PR > 210 millisecond [msec], QRS > 110 msec), or laboratory test results that required medical treatment at Screening or Baseline A prolonged QT/QTc interval (QTcF > 450 msec) as demonstrated by ECGs at Screening or Baseline Systolic blood pressure > 130 millimetres of mercury (mmHg) or diastolic blood pressure > 85 mmHg at Screening or Baseline Heart rate less than (<) 45 beats per minute (beats/min) or >100 beats/min at Screening or Baseline Known history of clinically significant drug allergy at Screening or Baseline Known history of food allergies or presently experiencing significant seasonal or perennial allergy at Screening or Baseline Known to be human immunodeficiency virus (HIV) positive at Screening Active viral hepatitis (A, B, or C) as demonstrated by positive serology at Screening History of drug or alcohol dependency or abuse within the 2 years before Screening, or those who have a positive urine drug or alcohol test at Screening or Baseline Use of tobacco or nicotine-containing products within 4 weeks before dosing Currently enrolled in another clinical trial or used any investigational drug or device within 30 days (or 5 half-lives, whichever is longer) preceding informed consent Engagement in strenuous exercise within 2 weeks before dosing (example, marathon runners, weight lifters) Intake of caffeinated beverages or caffeinated food within 72 hours before dosing Intake of nutritional supplements, juice, and herbal preparations or other foods or beverages that may affect the various drug metabolizing enzymes and transporters (example, alcohol, grapefruit, grapefruit juice, grapefruit-containing beverages, apple or orange juice, vegetables from the mustard green family [example, kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, mustard], and charbroiled meats) within 1 week before dosing Intake of herbal preparations containing St. John's Wort within 4 weeks before dosing Intake of over-the-counter (OTC) medications within 14 days (or 5 half-lives, whichever is longer) before dosing unless the investigator and sponsor medical monitor consider that they do not compromise participant safety or study assessments Use of any prescription drugs within 4 weeks before dosing Use of illegal recreational drugs Receipt of blood products within 4 weeks, or donation of blood within 8 weeks, or donation of plasma within 1 week of dosing
Facility Information:
Facility Name
Covance Clinical Research Unit Inc.
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53704
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.

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A Study to Determine the Metabolism and Elimination of [14C]E2027 in Healthy Male Participants

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