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
- Registration Number
- NCT04271488
- Lead Sponsor
- Eisai Co., Ltd.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 18
- 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.
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort A: Mild Hepatic Impairment (Child Pugh Class A) Tasurgratinib 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. Cohort B: Moderate Hepatic Impairment (Child Pugh Class B) Tasurgratinib 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. Cohort C: Healthy Participants (Control) Tasurgratinib 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.
- Primary Outcome Measures
Name Time Method Cmax: Maximum Observed Plasma Concentration of Tasurgratinib Day 1: 0-144 hours postdose AUC(0-inf): Area Under the Plasma Concentration versus Time Curve from Time 0 to Infinity of Tasurgratinib 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 Day 1: 0-144 hours postdose
- Secondary Outcome Measures
Name Time Method T1/2: Terminal Phase Plasma Half-life of Tasurgratinib and its Metabolite 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 Day 1: 0-144 hours postdose fu: Plasma Protein Unbound Fraction of Tasurgratiniband its Metabolite Day 1: 0-144 hours postdose CLu/F: Apparent Clearance Relative to the Unbound Plasma Concentration of Based on AUCu of Tasurgratinib Day 1: 0-144 hours postdose CL/F: Apparent Total Body Clearance of Tasurgratinib Day 1: 0-144 hours postdose Vz/F : Apparent Volume of Distribution at Terminal Phase of Tasurgratinib 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 Day 1: 0-144 hours postdose AUCu: AUC(0-inf) Values Adjusted by Unbound Fraction in Plasma of Tasurgratinib Day 1: 0-144 hours postdose Tmax: Time to Reach Maximum Plasma Concentration of Tasurgratinib and its Metabolite Day 1: 0-144 hours postdose
Trial Locations
- Locations (6)
Eisai Trial Site #6
🇯🇵Hakata, Fukuoka, Japan
Eisai Trial Site #5
🇯🇵Kofu, Yamanashi, Japan
Eisai Trial Site #4
🇯🇵Kurume, Fukuoka, Japan
Eisai Trial Site #2
🇯🇵Yufu, Oita, Japan
Eisai Trial Site #3
🇯🇵Bunkyō-Ku, Tokyo, Japan
Eisai Trial Site #1
🇯🇵Minato-Ku, Tokyo, Japan