Study to Evaluate the Pharmacokinetics (PK) of E7090 and Its Metabolite in Participants With Mild and Moderate Hepatic Impairment Compared to Healthy Participants
Study Details
Study Description
Brief Summary
The primary purpose of the study is to evaluate the effects of mild and moderate hepatic impairment on PK of E7090 after a single dose administration.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort A: Mild Hepatic Impairment (Child Pugh Class A) Participants with mild hepatic impairment will receive a single 35 milligram (mg) tablet of E7090 in the morning with 150 milliliters (mL) of water following an overnight fast of at least 10 hours. |
Drug: E7090
E7090 oral tablet.
|
| Experimental: Cohort B: Moderate Hepatic Impairment (Child Pugh Class B) Participants with moderate hepatic impairment will receive 10 mg dose of E7090 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. |
Drug: E7090
E7090 oral capsule.
|
| Experimental: Cohort C: Healthy Participants (Control) 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 E7090 in the morning with 150 mL of water following an overnight fast of at least 10 hours. |
Drug: E7090
E7090 oral tablet.
|
Outcome Measures
Primary Outcome Measures
- Cmax: Maximum Observed Plasma Concentration of E7090 [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 E7090 [Day 1: 0-144 hours postdose]
- AUC(0-inf): Area Under the Plasma Concentration versus Time Curve from Time 0 to Infinity of E7090 [Day 1: 0-144 hours postdose]
Secondary Outcome Measures
- Tmax: Time to Reach Maximum Plasma Concentration of E7090 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 E7090 and its Metabolite [Day 1: 0-144 hours postdose]
- T1/2: Terminal Phase Plasma Half-life of E7090 and its Metabolite [Day 1: 0-144 hours postdose]
- CL/F: Apparent Total Body Clearance of E7090 [Day 1: 0-144 hours postdose]
- Vz/F : Apparent Volume of Distribution at Terminal Phase of E7090 [Day 1: 0-144 hours postdose]
- AUC Metabolite Ratio: Ratio of AUC(0-inf) of M2 to AUC(0-inf) of E7090, Corrected for Molecular Weights [Day 1: 0-144 hours postdose]
- fu: Plasma Protein Unbound Fraction of E7090 and its Metabolite [Day 1: 0-144 hours postdose]
- AUCu: AUC(0-inf) Values Adjusted by Unbound Fraction in Plasma of E7090 [Day 1: 0-144 hours postdose]
- CLu/F: Apparent Clearance Relative to the Unbound Plasma Concentration of Based on AUCu of E7090 [Day 1: 0-144 hours postdose]
Eligibility Criteria
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
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Current evidence of Grade 2 or higher corneal disorder
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Current evidence of active macular disorder (example, Age-related macular degeneration, central serous chorioretinal disease)
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Known to be human immunodeficiency virus (HIV) positive at Screening.
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A prolonged QT/QTc interval ([QT interval using Fridericia's formula] QTcF greater than (>) 480 millisecond [ms]) demonstrated on ECG.
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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:
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Any significant acute medical illness (such as new conditions or exacerbation of pre-existing conditions) within 8 weeks of dosing.
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Presence of severe ascites, edema, or uncontrolled hepatic encephalopathy
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Eisai Trial Site #2 | Yufu | Oita | Japan | |
| 2 | Eisai Trial Site #3 | Bunkyō-Ku | Tokyo | Japan | |
| 3 | Eisai Trial Site #1 | Minato-Ku | Tokyo | Japan |
Sponsors and Collaborators
- Eisai Co., Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- E7090-J081-001