Clinical trial NCT04271488: 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
Overall status: RECRUITING
Phase: PHASE1
Conditions: Hepatic Impairment
Keywords: Hepatic Impairment
E7090
Tasurgratinib
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2020-02-17
Enrollment: 18
Sex: ALL
Minimum age (years): 20
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Cmax: Maximum Observed Plasma Concentration of Tasurgratinib
timeFrame: Day 1: 0-144 hours postdose
measure: AUC(0-t): Area Under the Plasma Concentration versus Time Curve from Time 0 to Time of Last Quantifiable Concentration of Tasurgratinib
timeFrame: Day 1: 0-144 hours postdose
measure: AUC(0-inf): Area Under the Plasma Concentration versus Time Curve from Time 0 to Infinity of Tasurgratinib
timeFrame: Day 1: 0-144 hours postdose
Secondary outcomes:
measure: Tmax: Time to Reach Maximum Plasma Concentration of Tasurgratinib and its Metabolite
timeFrame: Day 1: 0-144 hours postdose
measure: AUC(0-72Hours): Area Under the Plasma Concentration versus Time Curve from Time 0 to 72 Hours of Tasurgratinib and its Metabolite
timeFrame: Day 1: 0-144 hours postdose
measure: T1/2: Terminal Phase Plasma Half-life of Tasurgratinib and its Metabolite
timeFrame: Day 1: 0-144 hours postdose
measure: CL/F: Apparent Total Body Clearance of Tasurgratinib
timeFrame: Day 1: 0-144 hours postdose
measure: Vz/F : Apparent Volume of Distribution at Terminal Phase of Tasurgratinib
timeFrame: Day 1: 0-144 hours postdose
measure: AUC Metabolite Ratio: Ratio of AUC(0-inf) of M2 to AUC(0-inf) of Tasurgratinib, Corrected for Molecular Weights
timeFrame: Day 1: 0-144 hours postdose
measure: fu: Plasma Protein Unbound Fraction of Tasurgratiniband its Metabolite
timeFrame: Day 1: 0-144 hours postdose
measure: AUCu: AUC(0-inf) Values Adjusted by Unbound Fraction in Plasma of Tasurgratinib
timeFrame: Day 1: 0-144 hours postdose
measure: CLu/F: Apparent Clearance Relative to the Unbound Plasma Concentration of Based on AUCu of Tasurgratinib
timeFrame: Day 1: 0-144 hours postdose
Other outcomes:
Locations:
city: Hakata
country: Japan
facility: Eisai Trial Site #6
state: Fukuoka
city: Kurume
country: Japan
facility: Eisai Trial Site #4
state: Fukuoka
city: Yufu
country: Japan
facility: Eisai Trial Site #2
state: Oita
city: Bunkyō-Ku
country: Japan
facility: Eisai Trial Site #3
state: Tokyo
city: Minato-Ku
country: Japan
facility: Eisai Trial Site #1
state: Tokyo
city: Kofu
country: Japan
facility: Eisai Trial Site #5
state: Yamanashi
Study officials:
References: