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

Hepatic Impairment Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04271488
• Other study ID #: E7090-J081-001
• Status: Recruiting
• Phase: Phase 1
• Start date: February 27, 2020
• Est. completion date: November 30, 2024

Study information

• Verified date: October 2023
• Source: Eisai Inc.
• Contact: Inquiry Service.
• Email: eisai-chiken_hotline[@]hhc.eisai.co.jp
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 18
• Est. completion date: November 30, 2024
• Est. primary completion date: November 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 79 Years

Eligibility

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.

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.

Related Conditions & MeSH terms

• Hepatic Impairment
• Liver Diseases

Intervention

Drug:
• Tasurgratinib
Tasurgratinib oral tablet.
• Tasurgratinib
Tasurgratinib oral capsule.

Locations

Country	Name	City	State
Japan	Eisai Trial Site #3	Bunkyo-Ku	Tokyo
Japan	Eisai Trial Site #4	Kurume	Fukuoka
Japan	Eisai Trial Site #1	Minato-Ku	Tokyo
Japan	Eisai Trial Site #2	Yufu	Oita

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Co., Ltd.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cmax: Maximum Observed Plasma Concentration of Tasurgratinib		Day 1: 0-144 hours postdose
Primary	AUC(0-t): Area Under the Plasma Concentration versus Time Curve from Time 0 to Time of Last Quantifiable Concentration of Tasurgratinib		Day 1: 0-144 hours postdose
Primary	AUC(0-inf): Area Under the Plasma Concentration versus Time Curve from Time 0 to Infinity of Tasurgratinib		Day 1: 0-144 hours postdose
Secondary	Tmax: Time to Reach Maximum Plasma Concentration of Tasurgratinib and its Metabolite		Day 1: 0-144 hours postdose
Secondary	AUC(0-72Hours): Area Under the Plasma Concentration versus Time Curve from Time 0 to 72 Hours of Tasurgratinib and its Metabolite		Day 1: 0-144 hours postdose
Secondary	T1/2: Terminal Phase Plasma Half-life of Tasurgratinib and its Metabolite		Day 1: 0-144 hours postdose
Secondary	CL/F: Apparent Total Body Clearance of Tasurgratinib		Day 1: 0-144 hours postdose
Secondary	Vz/F : Apparent Volume of Distribution at Terminal Phase of Tasurgratinib		Day 1: 0-144 hours postdose
Secondary	AUC Metabolite Ratio: Ratio of AUC(0-inf) of M2 to AUC(0-inf) of Tasurgratinib, Corrected for Molecular Weights		Day 1: 0-144 hours postdose
Secondary	fu: Plasma Protein Unbound Fraction of Tasurgratiniband its Metabolite		Day 1: 0-144 hours postdose
Secondary	AUCu: AUC(0-inf) Values Adjusted by Unbound Fraction in Plasma of Tasurgratinib		Day 1: 0-144 hours postdose
Secondary	CLu/F: Apparent Clearance Relative to the Unbound Plasma Concentration of Based on AUCu of Tasurgratinib		Day 1: 0-144 hours postdose