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

Официальное название

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

Обзор

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.

Вмешательства

• Препарат Tasurgratinib
  Tasurgratinib oral tablet.
• Препарат Tasurgratinib
  Tasurgratinib oral capsule.

Первичные конечные точки

• Cmax: Maximum Observed Plasma Concentration of Tasurgratinib [Срок оценки: Day 1: 0-144 hours postdose]
• AUC(0-t): Area Under the Plasma Concentration versus Time Curve from Time 0 to Time of Last Quantifiable Concentration of Tasurgratinib [Срок оценки: Day 1: 0-144 hours postdose]
• AUC(0-inf): Area Under the Plasma Concentration versus Time Curve from Time 0 to Infinity of Tasurgratinib [Срок оценки: Day 1: 0-144 hours postdose]

Вторичные конечные точки (9)

• Tmax: Time to Reach Maximum Plasma Concentration of Tasurgratinib and its Metabolite [Срок оценки: Day 1: 0-144 hours postdose]
• AUC(0-72Hours): Area Under the Plasma Concentration versus Time Curve from Time 0 to 72 Hours of Tasurgratinib and its Metabolite [Срок оценки: Day 1: 0-144 hours postdose]
• T1/2: Terminal Phase Plasma Half-life of Tasurgratinib and its Metabolite [Срок оценки: Day 1: 0-144 hours postdose]
• CL/F: Apparent Total Body Clearance of Tasurgratinib [Срок оценки: Day 1: 0-144 hours postdose]
• Vz/F : Apparent Volume of Distribution at Terminal Phase of Tasurgratinib [Срок оценки: Day 1: 0-144 hours postdose]
• AUC Metabolite Ratio: Ratio of AUC(0-inf) of M2 to AUC(0-inf) of Tasurgratinib, Corrected for Molecular Weights [Срок оценки: Day 1: 0-144 hours postdose]
• fu: Plasma Protein Unbound Fraction of Tasurgratiniband its Metabolite [Срок оценки: Day 1: 0-144 hours postdose]
• AUCu: AUC(0-inf) Values Adjusted by Unbound Fraction in Plasma of Tasurgratinib [Срок оценки: Day 1: 0-144 hours postdose]
• CLu/F: Apparent Clearance Relative to the Unbound Plasma Concentration of Based on AUCu of Tasurgratinib [Срок оценки: Day 1: 0-144 hours postdose]

Критерии участия

Критерии включения

• 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.

Критерии исключения

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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Япония · 8 центров

• Eisai Trial Site #6 — Hakata
• Eisai Trial Site #4 — Kurume
• Eisai Trial Site #2 — Yuhu
• Eisai Trial Site #3 — Bukyo-ku
• Eisai Trial Site #1 — Mintato-ku
• Eisai Trial Site #8 — Shinjuku-ku
• Eisai Trial Site #5 — Kofu
• Eisai Trial Site #7 — Kyoto

Идентификаторы

NCT: NCT04271488 · E7090-J081-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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