A Phase 1, Open-Label, Single-Dose, Pharmacokinetic and Safety Study of E7080 (24 mg) Administered to Subjects With Mild, Moderate, and Severe Renal Impairment and to Healthy Subjects

Subjects who meet any of the following criteria will be excluded from this study:

All Subjects:

1. Use of any new medication, including multivitamins, or investigational drug within 14 days prior to the drug administration, or within five times the elimination half-life, whichever is longest, except combined oral contraceptives and occasional use of paracetamol or ibuprofen within 14 days and any local anesthetic within 3 days before study drug administration. Current over-the-counter (OTC) drugs and prescription medication use is permitted, but must be stable and consistent for at least 14 days prior to Screening and throughout the study treatment period.

2. Positive HIV screening test

3. Presence of acute, active liver disease or acute liver injury as indicated by (1) an abnormal liver function test, or (2) clinical or laboratory signs of acute, active hepatitis A, B, or C

4. Systolic blood pressure greater than or equal to 160 mm Hg and/or diastolic blood pressure greater than or equal to 100 mm Hg for healthy subjects and subjects with mild renal impairment; systolic blood pressure greater than or equal to 180 mm Hg and/or diastolic blood pressure greater than or equal to 110 mm Hg for subjects with moderate and severe renal impairment. Readings are to be confirmed by repeat determinations one hour after the first measurement.

Healthy Subjects:

1. Subjects who had a clinically significant illness which required medical treatment within 8 weeks or a clinically significant infection within 4 weeks of dosing

2. Subjects with a history of myocardial infarction or active ischemic heart disease

3. Subjects with a disease that may influence the outcome of the study, such as psychiatric disorders and disorders of the gastrointestinal tract, liver, kidney, respiratory system, endocrine system, hematological system, neurological system, or cardiovascular system, or subjects who have a congenital abnormality in metabolism within 4 weeks prior to dosing

4. Gastrointestinal malabsorption or any other condition that may affect PK profiles of E7080 including a history of gastrointestinal surgery (hepatectomy, digestive organ resection, etc.) (Appendectomy and cholecystectomy are, however, permitted.)

5. Subjects with a history of clinically significant drug or food allergies or presently experiencing significant seasonal allergies

6. Subjects who experienced a weight loss or gain of greater than 10% between Screening and prior to dosing

7. Subjects with a QTc interval greater than 450 msec demonstrated on repeated electrocardiogram (ECG) at Screening

8. Subjects with hemoglobin level less than 12.0 g/dL

9. Significant findings revealed by the history, physical or clinical laboratory testing

10. Subjects with a known or suspected history of drug or alcohol misuse within 6 months prior to Screening, or who have a positive urine drug or alcohol test at Screening or Baseline

11. Subjects who have consumed caffeinated beverages or food within 72 hours prior to dosing

12. Receipt of another investigational drug or device within 4 weeks prior to dosing or five half-lives of the other investigational drug, whichever is longer

13. Subjects who received blood products within 4 weeks, or donated blood within 8 weeks, or donated plasma within one week of dosing

14. Subjects who have engaged in heavy exercise within 2 weeks prior to check-in (e.g., marathon runners, weight lifters, etc.)

15. Subjects who are unwilling to abide by the requirements of the study, or in the opinion of the investigator, are not likely to complete the study.

Subjects with Renal Impairment:

1. A history of renal transplant

2. Known significant bleeding diathesis (e.g., history of recent bleeding from esophageal varices), which could preclude multiple venipuncture or deep intramuscular injection

4. Subjects who had a clinically significant illness, where said illness is unrelated to their renal impairment, which required medical treatment within 8 weeks or a clinically significant infection within 4 weeks of dosing

5. Subjects with a history of significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II; unstable angina; myocardial infarction or stroke within 6 months of the first dose of study drug; or cardiac arrhythmia requiring medical treatment

6. Subjects with a disease that may influence the outcome of the study, such as psychiatric disorders and disorders of the gastrointestinal tract, liver, kidney, respiratory system, endocrine system, hematological system, neurological system, or cardiovascular system, or subjects who have a congenital abnormality in metabolism within 4 weeks prior to dosing

7. Gastrointestinal malabsorption or any other condition that may affect PK profiles of E7080 including a history of gastrointestinal surgery (hepatectomy, digestive organ resection, etc.). (Appendectomy and cholecystectomy are, however, permitted.)

8. Subjects with a known history of clinically significant drug or food allergies or presently experiencing significant seasonal allergies

9. Subjects who experienced a weight loss or gain of greater than 10% between Screening and prior to dosing

10. Significant findings revealed by the history, physical or clinical laboratory testing where said findings are unrelated to the subject's renal impairment

11. Subjects with a known or suspected history of drug or alcohol misuse within 6 months prior to Screening, or who have a positive urine drug or alcohol test at Screening or Baseline

12. Subjects who have consumed caffeinated beverages or food within 72 hours prior to dosing

13. Receipt of another investigational drug or device within 4 weeks prior to dosing or five half-lives of the other investigational drug, whichever is longer

14. Subjects who received blood products within 4 weeks, or donated blood within 8 weeks, or donated plasma within one week of dosing

15. Subjects who have engaged in heavy exercise within 2 weeks prior to check-in (e.g., marathon runners, weight lifters, etc.)

16. Subjects who are unwilling to abide by the requirements of the study, or in the opinion of the investigator, are not likely to complete the study.

A Phase 1, Open-Label, Single-Dose, Pharmacokinetic and Safety Study of E7080 (24 mg) Administered to Subjects With Mild, Moderate, and Severe Renal Impairment and to Healthy Subjects

What this study is about

A Phase 1, Open-Label, Single-Dose, Pharmacokinetic and Safety Study of E7080 (24 mg) Administered to Subjects With Mild, Moderate, and Severe Renal Impairment and to Healthy Subjects

What this study is about