A Pharmacokinetic and Safety Study of E7080 in Subjects With Mild (10 mg), Moderate (10 mg), and Severe Hepatic Impairment (5 mg) and Normal Hepatic Function (10 mg)

NCT02421042 | Completed Phase 1

• 1 other identifier: E7080-A001-006
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 5

Brief Summary

This is a multi-center, open-label, non-randomized, single-dose, sequential-cohort study in subjects with varying degrees of hepatic impairment, classified according to the Child-Pugh system, who will be matched with normal healthy subjects as controls.

Conditions

Hepatic Impairment; Hepatic Function

Keywords

Hepatic Impairment; Hepatic Function

Outcome Measures

Primary Outcomes (4)

• Pharmacokinetics of lenvatinib: Cmax

  Plasma concentrations of lenvatinib (free and total) and its metabolites, M1, M2, M3, and M5, (total) and urine concentrations of lenvatinib (total) and its metabolites, M1, M2, M3, and M5, (total) will be assessed.

  336 hours post study drug administration

• Pharmacokinetics of lenvatinib: AUC(0-t)

  Plasma concentrations of lenvatinib (free and total) and its metabolites, M1, M2, M3, and M5, (total) and urine concentrations of lenvatinib (total) and its metabolites, M1, M2, M3, and M5, (total) will be assessed.

  336 hours post study drug administration

• Pharmacokinetics of lenvatinib: AUC(0-inf)

  Plasma concentrations of lenvatinib (free and total) and its metabolites, M1, M2, M3, and M5, (total) and urine concentrations of lenvatinib (total) and its metabolites, M1, M2, M3, and M5, (total) will be assessed.

  336 hours post study drug administration

• Safety of lenvatinib as assessed by Vital Signs

  Screening, Baseline and Treatment [upto Study discharge (17 days plus or minus 2 days)]

Secondary Outcomes (3)

• Safety of lenvatinib as assessed by Adverse Events/Serious Adverse Events

  Screening, Baseline and Treatment [upto Study discharge (17 days plus or minus 2 days)]

• Safety of lenvatinib as assessed by Laboratory Values

  Screening, Baseline and Treatment [upto Study discharge (17 days plus or minus 2 days)]

• Safety of lenvatinib as assessed by ECGs

  Screening, Baseline and Treatment [upto Study discharge (17 days plus or minus 2 days)]

Study Arms (1)

Lenvatinib

EXPERIMENTAL

Subjects determined to be eligible for the protocol will receive either a 5- or 10-mg single oral dose of lenvatinib on Day 1, depending on their hepatic status \[Mild (10 mg), Moderate (10 mg), and Severe Hepatic Impairment (5 mg) and Normal Hepatic Function (10 mg)\].

Drug: Lenvatinib

Interventions

Lenvatinib DRUG

5- or 10-mg single oral dose of E7080, depending on their hepatic status \[Mild (10 mg), Moderate (10 mg), and Severe Hepatic Impairment (5 mg) and Normal Hepatic Function (10 mg)\].

Also known as: E7080

Lenvatinib

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All subjects must meet all of the following criteria to be included in this study:
• Male or female subjects aged 18 to 70, inclusive
• BMI greater than or equal to 18 to lesser than or equal to 35 kg/m2, inclusive
• Non-smokers and smokers who smoke no more than 10 cigarettes per day
• All females must have a negative serum beta human chorionic gonadotropin (B-hCG) test result and a negative urine pregnancy test result at Screening and Baseline. Females of childbearing potential must agree to use a highly effective method of contraception (e.g., abstinence, an intrauterine device \[IUD\], a barrier method such as a condom plus spermicide or condom plus diaphragm with spermicide, a contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia) throughout the entire study period and for 30 days after study drug discontinuation. The only subjects who will be exempt from this requirement are postmenopausal females (defined as at least 12 months' consecutive amenorrhea, in the appropriate age group, without other known or suspected primary cause) or subjects who have been sterilized surgically or who are otherwise proven sterile (i.e., bilateral tubal ligation with surgery at least 1 month prior to dosing, hysterectomy, or bilateral oophorectomy with surgery at least 1 month prior to dosing). All women who are of reproductive potential and who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product for at least 4 weeks prior to dosing and must continue to use the same contraceptive during the study and for 30 days after study drug discontinuation.
• Male subjects who are not abstinent or have not undergone a successful vasectomy, who are partners of women of childbearing potential, must use, or their partners must use, a highly effective method of contraception (e.g., condom plus spermicide, condom plus diaphragm with spermicide, IUD) starting for at least one menstrual cycle prior to starting study drug(s) and throughout the entire study period and for 30 days (longer if appropriate) after the last dose of study drug.
• Voluntarily provide written informed consent prior to any study procedures
• Are willing and able to comply with all aspects of the protocol for the duration of the study.
• Subjects must have a diagnosis of liver cirrhosis that has been stable, without any change in disease status, for 60 days prior to study screening, as determined by the investigator.
• Subjects must have a platelet count greater than 30,000 cells/mm3; if platelet count is lesser than 30,000 cells/mm3, the subject may be enrolled with joint approval of the principal investigator (PI) and medical monitor based on subject history and stability.
• Subjects must have no history of clinically relevant disease or condition (e.g., significant cardiac or renal dysfunction, diseases of the gastrointestinal tract or conditions which may impact drug absorption), as determined by the investigator.
• Subjects must have a total score on the Child-Pugh classification system between 5 and 6 (Group 1, mild impairment), 7 to 9 (Group 2, moderate impairment), and 10 to 15 (Group 3, severe impairment).
• Subjects with a history of Type I or Type II diabetes are permissible, providing that, in the opinion of the investigator, they have stable disease. Subjects receiving insulin therapy are permissible provided that they have been on a stable treatment for at least 2 weeks prior to study enrollment and continuing through the study.

You may not qualify if:

• All subjects who meet any of the following criteria will be excluded from participation in the study:
• Use of any new medication, including multi-vitamins, or an 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 Vitamin K supplements and thiamine for hepatic impairment subjects; any local anesthetic within 3 days before study drug administration. Current over-the-counter (OTC) 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.
• Positive human immunodeficiency virus (HIV) screening test
• QTc interval calculated by Fridericia's formula (QTcF) greater than 480 ms at screening or baseline
• Presence of acute active liver disease or acute liver injury as indicated by (1) an abnormal liver function test, or (2) clinical and/or laboratory signs of acute, active hepatitis A, B, and/or C. Subjects with stable, chronic, active hepatitis B or C may be enrolled if the investigator deems them to be appropriate.
• Additionally normal healthy subjects who meet any of the following criteria will be excluded from participation in the study:
• Presence of clinically significant illness requiring treatment
• History of gastrointestinal surgery (cholecystectomy and appendectomy are, however, permitted)
• History of significant drug, food, or seasonal allergies
• Weight change during the Pretreatment Phase
• Significant findings revealed by the history, physical or clinical laboratory testing
• Alcohol misuse
• Caffeine intake within 72 hours of lenvatinib administration
• Participation in another clinical trial within 4 weeks of lenvatinib administration
• Receipt or donation of blood or blood products within 4 to 8 weeks of lenvatinib administration

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (5)

Unknown Facility

Miami, Florida, 33014, United States

Location

Unknown Facility

Miami, Florida, 33169, United States

Location

Unknown Facility

Orlando, Florida, 32809, United States

Location

Unknown Facility

Minneapolis, Minnesota, 55404, United States

Location

Unknown Facility

Knoxville, Tennessee, 37920, United States

Location

MeSH Terms

Interventions

lenvatinib

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2014
• First Posted: April 20, 2015
• Study Start: June 1, 2011
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: May 5, 2015

Record last verified: 2015-05

Locations

US (5)