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Study to Evaluate the Pharmacokinetics (PK) of E7090 (Herein Referred to as Tasurgratinib) and Its Metabolite in Participants With Mild and Moderate Hepatic Impairment Compared to Healthy Participants

Primary Purpose

Hepatic Impairment

Status
Recruiting
Phase
Phase 1
Locations
Japan
Study Type
Interventional
Intervention
Tasurgratinib
Tasurgratinib
Sponsored by
Eisai Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatic Impairment focused on measuring Hepatic Impairment, E7090, Tasurgratinib

Eligibility Criteria

20 Years - 79 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  1. Body mass index (BMI) between 18 to 40 kilogram per square meter (kg/m^2).
  2. For Cohorts A and B: stable hepatic impairment conforming to Child-Pugh classification A and B.
  3. For Cohort C: healthy participants matched to participants with hepatic impairment with regard to age (+/-10 years), body weight (+/-20 percent [%]), race and gender, and as determined by no clinically significant deviation from normal in medical history, physical examination, electrocardiogram (ECG), and clinical laboratory determinations.

Exclusion Criteria:

Key Exclusion for all Participants:

  1. Following ocular disorders

    1. Current evidence of Grade 2 or higher corneal disorder
    2. Current evidence of active macular disorder (example, Age-related macular degeneration, central serous chorioretinal disease)
  2. Known to be human immunodeficiency virus (HIV) positive at Screening.
  3. A prolonged QT/QTc interval ([QT interval using Fridericia's formula] QTcF greater than (>) 480 millisecond [ms]) demonstrated on ECG.
  4. Participants who need the use of drugs or foods that strongly inhibits or induces the metabolizing enzyme Cytochrome P450, family 3, subfamily A (CYP3A).

Additional Exclusion Criteria for Hepatically Impaired Participants (Cohorts A and B)

In addition to the Exclusion Criteria above for all participants, other standard exclusion criteria for participants with hepatic impairment will be used. These include:

  1. Any significant acute medical illness (such as new conditions or exacerbation of pre-existing conditions) within 8 weeks of dosing.
  2. Presence of severe ascites, edema, or uncontrolled hepatic encephalopathy
  3. The participant's standard therapy/concomitant medication for diseases related to hepatic disease has not remained stable/unchanged for at least two weeks before dosing of study drug.

Additional Exclusion Criteria for Healthy participants (Cohort C)

In addition to the Exclusion Criteria for all participants, other standard exclusion criteria for healthy participants in Phase 1 studies will be used. These include:

  1. Syphilis as demonstrated by positive serology at Screening.
  2. Any abnormal finding based on physical examination, assessment of vital signs, ECG, or laboratory test results that requires treatment or clinical follow up based on investigators opinion.

Sites / Locations

  • Eisai Trial Site #4
  • Eisai Trial Site #2Recruiting
  • Eisai Trial Site #3Recruiting
  • Eisai Trial Site #1Recruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Cohort A: Mild Hepatic Impairment (Child Pugh Class A)

Cohort B: Moderate Hepatic Impairment (Child Pugh Class B)

Cohort C: Healthy Participants (Control)

Arm Description

Participants with mild hepatic impairment will receive a single 35 milligram (mg) tablet of tasurgratinib in the morning with 150 milliliters (mL) of water following an overnight fast of at least 10 hours.

Participants with moderate hepatic impairment will receive 10 mg dose of tasurgratinib as capsule (2 capsules each of 5 mg) in the morning with 150 mL of water following an overnight fast of at least 10 hours.

Healthy participants matched to participants with hepatic impairment in Cohorts A and B (matched with regards to age, race, gender and body weight) will receive a single 35 mg tablet of tasurgratinib in the morning with 150 mL of water following an overnight fast of at least 10 hours.

Outcomes

Primary Outcome Measures

Cmax: Maximum Observed Plasma Concentration of Tasurgratinib
AUC(0-t): Area Under the Plasma Concentration versus Time Curve from Time 0 to Time of Last Quantifiable Concentration of Tasurgratinib
AUC(0-inf): Area Under the Plasma Concentration versus Time Curve from Time 0 to Infinity of Tasurgratinib

Secondary Outcome Measures

Tmax: Time to Reach Maximum Plasma Concentration of Tasurgratinib and its Metabolite
AUC(0-72Hours): Area Under the Plasma Concentration versus Time Curve from Time 0 to 72 Hours of Tasurgratinib and its Metabolite
T1/2: Terminal Phase Plasma Half-life of Tasurgratinib and its Metabolite
CL/F: Apparent Total Body Clearance of Tasurgratinib
Vz/F : Apparent Volume of Distribution at Terminal Phase of Tasurgratinib
AUC Metabolite Ratio: Ratio of AUC(0-inf) of M2 to AUC(0-inf) of Tasurgratinib, Corrected for Molecular Weights
fu: Plasma Protein Unbound Fraction of Tasurgratiniband its Metabolite
AUCu: AUC(0-inf) Values Adjusted by Unbound Fraction in Plasma of Tasurgratinib
CLu/F: Apparent Clearance Relative to the Unbound Plasma Concentration of Based on AUCu of Tasurgratinib

Full Information

First Posted
February 13, 2020
Last Updated
October 5, 2023
Sponsor
Eisai Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT04271488
Brief Title
Study to Evaluate the Pharmacokinetics (PK) of E7090 (Herein Referred to as Tasurgratinib) and Its Metabolite in Participants With Mild and Moderate Hepatic Impairment Compared to Healthy Participants
Official Title
An Open-label Parallel-Group Study to Evaluate Pharmacokinetics of E7090 and Its Metabolite in Subjects With Mild and Moderate Hepatic Impairment Compared to Healthy Subjects
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 27, 2020 (Actual)
Primary Completion Date
August 1, 2024 (Anticipated)
Study Completion Date
August 1, 2024 (Anticipated)

3. Sponsor/Collaborators

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

4. Oversight

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

5. Study Description

Brief Summary
The primary purpose of the study is to evaluate the effects of mild and moderate hepatic impairment on PK of tasurgratinib after a single dose administration.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatic Impairment
Keywords
Hepatic Impairment, E7090, Tasurgratinib

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
18 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort A: Mild Hepatic Impairment (Child Pugh Class A)
Arm Type
Experimental
Arm Description
Participants with mild hepatic impairment will receive a single 35 milligram (mg) tablet of tasurgratinib in the morning with 150 milliliters (mL) of water following an overnight fast of at least 10 hours.
Arm Title
Cohort B: Moderate Hepatic Impairment (Child Pugh Class B)
Arm Type
Experimental
Arm Description
Participants with moderate hepatic impairment will receive 10 mg dose of tasurgratinib as capsule (2 capsules each of 5 mg) in the morning with 150 mL of water following an overnight fast of at least 10 hours.
Arm Title
Cohort C: Healthy Participants (Control)
Arm Type
Experimental
Arm Description
Healthy participants matched to participants with hepatic impairment in Cohorts A and B (matched with regards to age, race, gender and body weight) will receive a single 35 mg tablet of tasurgratinib in the morning with 150 mL of water following an overnight fast of at least 10 hours.
Intervention Type
Drug
Intervention Name(s)
Tasurgratinib
Intervention Description
Tasurgratinib oral tablet.
Intervention Type
Drug
Intervention Name(s)
Tasurgratinib
Intervention Description
Tasurgratinib oral capsule.
Primary Outcome Measure Information:
Title
Cmax: Maximum Observed Plasma Concentration of Tasurgratinib
Time Frame
Day 1: 0-144 hours postdose
Title
AUC(0-t): Area Under the Plasma Concentration versus Time Curve from Time 0 to Time of Last Quantifiable Concentration of Tasurgratinib
Time Frame
Day 1: 0-144 hours postdose
Title
AUC(0-inf): Area Under the Plasma Concentration versus Time Curve from Time 0 to Infinity of Tasurgratinib
Time Frame
Day 1: 0-144 hours postdose
Secondary Outcome Measure Information:
Title
Tmax: Time to Reach Maximum Plasma Concentration of Tasurgratinib and its Metabolite
Time Frame
Day 1: 0-144 hours postdose
Title
AUC(0-72Hours): Area Under the Plasma Concentration versus Time Curve from Time 0 to 72 Hours of Tasurgratinib and its Metabolite
Time Frame
Day 1: 0-144 hours postdose
Title
T1/2: Terminal Phase Plasma Half-life of Tasurgratinib and its Metabolite
Time Frame
Day 1: 0-144 hours postdose
Title
CL/F: Apparent Total Body Clearance of Tasurgratinib
Time Frame
Day 1: 0-144 hours postdose
Title
Vz/F : Apparent Volume of Distribution at Terminal Phase of Tasurgratinib
Time Frame
Day 1: 0-144 hours postdose
Title
AUC Metabolite Ratio: Ratio of AUC(0-inf) of M2 to AUC(0-inf) of Tasurgratinib, Corrected for Molecular Weights
Time Frame
Day 1: 0-144 hours postdose
Title
fu: Plasma Protein Unbound Fraction of Tasurgratiniband its Metabolite
Time Frame
Day 1: 0-144 hours postdose
Title
AUCu: AUC(0-inf) Values Adjusted by Unbound Fraction in Plasma of Tasurgratinib
Time Frame
Day 1: 0-144 hours postdose
Title
CLu/F: Apparent Clearance Relative to the Unbound Plasma Concentration of Based on AUCu of Tasurgratinib
Time Frame
Day 1: 0-144 hours postdose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Body mass index (BMI) between 18 to 40 kilogram per square meter (kg/m^2). For Cohorts A and B: stable hepatic impairment conforming to Child-Pugh classification A and B. For Cohort C: healthy participants matched to participants with hepatic impairment with regard to age (+/-10 years), body weight (+/-20 percent [%]), race and gender, and as determined by no clinically significant deviation from normal in medical history, physical examination, electrocardiogram (ECG), and clinical laboratory determinations. Exclusion Criteria: Key Exclusion for all Participants: Following ocular disorders Current evidence of Grade 2 or higher corneal disorder Current evidence of active macular disorder (example, Age-related macular degeneration, central serous chorioretinal disease) Known to be human immunodeficiency virus (HIV) positive at Screening. A prolonged QT/QTc interval ([QT interval using Fridericia's formula] QTcF greater than (>) 480 millisecond [ms]) demonstrated on ECG. Additional Exclusion Criteria for Hepatically Impaired Participants (Cohorts A and B) In addition to the Exclusion Criteria above for all participants, other standard exclusion criteria for participants with hepatic impairment will be used. These include: Any significant acute medical illness (such as new conditions or exacerbation of pre-existing conditions) within 8 weeks of dosing. Presence of severe ascites, edema, or uncontrolled hepatic encephalopathy The participant's standard therapy/concomitant medication for diseases related to hepatic disease has not remained stable/unchanged for at least two weeks before dosing of study drug. Additional Exclusion Criteria for Healthy participants (Cohort C) In addition to the Exclusion Criteria for all participants, other standard exclusion criteria for healthy participants in Phase 1 studies will be used. These include: Syphilis as demonstrated by positive serology at Screening. Any abnormal finding based on physical examination, assessment of vital signs, ECG, or laboratory test results that requires treatment or clinical follow up based on investigators opinion.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Inquiry Service.
Email
eisai-chiken_hotline@hhc.eisai.co.jp
Facility Information:
Facility Name
Eisai Trial Site #4
City
Kurume
State/Province
Fukuoka
Country
Japan
Individual Site Status
Terminated
Facility Name
Eisai Trial Site #2
City
Yufu
State/Province
Oita
Country
Japan
Individual Site Status
Recruiting
Facility Name
Eisai Trial Site #3
City
Bunkyō-Ku
State/Province
Tokyo
Country
Japan
Individual Site Status
Recruiting
Facility Name
Eisai Trial Site #1
City
Minato-Ku
State/Province
Tokyo
Country
Japan
Individual Site Status
Recruiting

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/.

Learn more about this trial

Study to Evaluate the Pharmacokinetics (PK) of E7090 (Herein Referred to as Tasurgratinib) and Its Metabolite in Participants With Mild and Moderate Hepatic Impairment Compared to Healthy Participants

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