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

NCT02199379 | Completed Phase 1

• 1 other identifier: E7080-A001-005
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this multicenter, open-label, non-randomized, single, oral dose, sequential-cohort study was to determine pharmacokinetics and safety of lenvatinib (24 mg) administered to healthy subjects and to subjects with renal impairment.

Conditions

Renal Impairment; Disease Severity

Keywords

renal impairment; disease severity

Outcome Measures

Primary Outcomes (3)

• Pharmacokinetics of lenvatinib: Cmax

  Day 1 to Day 8

• Pharmacokinetics of lenvatinib: AUC(0-inf)

  Day 1 to Day 8

• Pharmacokinetics of lenvatinib: AUC(0-t)

  Day 1 to Day 8

Secondary Outcomes (7)

• Safety as Measured by Outcome of all Adverse Events (AEs)

  Screening, Baseline and Treatment period (Day 1 to Day 8)

• Safety as Measured by Outcome of treatment-emergent AEs (TEAEs)

  Screening, Baseline and Treatment period (Day 1 to Day 8)

• Safety as Measured by Outcome of serious adverse events (SAEs)

  Screening, Baseline and Treatment period (Day 1 to Day 8)

• Safety as Measured by Laboratory Values

  Screening, Baseline and Treatment period (Day 1 to Day 8)

• Safety as Measured by vital signs

  Screening, Baseline and Treatment period (Day 1 to Day 8)

Study Arms (1)

Lenvatinib

EXPERIMENTAL

Lenvatinib will be taken as a single dose of 24 mg consisting of 2 x 10 mg and 1 x 4 mg capsules. Treatment will be administered orally with 240 mL of water following a 10-hour overnight fast.

Drug: Lenvatinib

Interventions

Lenvatinib DRUG

Lenvatinib will be taken as a single dose of 24 mg consisting of 2 x 10 mg and 1 x 4 mg capsules. Treatment will be administered orally with 240 mL of water following a 10-hour overnight fast.

Also known as: E7080

Lenvatinib

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All subjects should meet all of the following criteria to be included in this study:
• Male or female subjects, ages 18 to 79, inclusive, at the time of informed consent
• BMI, 18 to 40 kg/m2, inclusive, at Screening
• Nonsmokers and smokers who smoke no more than 10 cigarettes per day
• All females must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of beta-human chorionic gonadotropin \[B-hCG\] at the Screening Visit or within 72 hours before the first dose of study drug). Females of child-bearing potential, if not practicing total abstinence or having a vasectomised partner with confirmed azoospermia, must agree to use two highly effective methods of contraception: e.g., 1) an intrauterine device (IUD) or intrauterine system (IUS); 2) a barrier method such as a condom or occlusive cup (diaphragm or cervical/vault caps) plus spermicide (foam, gel, cream, etc.); 3) oral, injected, or implanted hormonal contraceptives throughout the entire study period and for 30 days after study drug discontinuation. Use of a double-barrier method (i.e., use at the same time of a condom plus occlusive cup \[diaphragm or cervical/vault caps\] plus spermicide \[foam, gel, cream, etc.\]) is accepted as two highly effective methods of contraception. The only subjects who will be exempt from this requirement are postmenopausal women (defined as women who have been amenorrheic for at least 12 consecutive months, 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, total 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.
• Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol.
• \. Creatinine clearance greater than or equal to 90 mL/min.
• Subjects must have a diagnosis of renal impairment that has been stable, without any change in disease status, for 60 days prior to study screening, as determined by the investigator.
• Mild (creatinine clearance, 60-89 mL/min), moderate (creatinine clearance, 30-59 mL/min), or severe (creatinine clearance, 15-29 mL/min) renal impairment
• Other than renal impairment, subjects must have no history of clinically relevant disease or condition (e.g., significant cardiac or hepatic dysfunction, diseases of the gastrointestinal tract or conditions which may impact drug absorption), as determined by the investigator.
• 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.
• QT interval corrected for heart rate (QTc) calculated by Fridericia's formula (QTcF) interval lesser than or equal to 500 msec at Screening and Baseline.
• Subjects may be enrolled with joint approval of the principal investigator (PI) and medical monitor based on subject history and stability of the renal impairment.

You may not qualify if:

• Subjects who meet any of the following criteria will be excluded from this study:
• All Subjects:
• 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.
• Positive HIV screening test
• 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
• 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:
• Subjects who had a clinically significant illness which required medical treatment within 8 weeks or a clinically significant infection within 4 weeks of dosing
• Subjects with a history of myocardial infarction or active ischemic heart disease
• 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
• 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.)
• Subjects with a history of clinically significant drug or food allergies or presently experiencing significant seasonal allergies
• Subjects who experienced a weight loss or gain of greater than 10% between Screening and prior to dosing
• Subjects with a QTc interval greater than 450 msec demonstrated on repeated electrocardiogram (ECG) at Screening
• Subjects with hemoglobin level less than 12.0 g/dL

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (3)

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

Conditions

Renal Insufficiency

Interventions

lenvatinib

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Design

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

Study Record Dates

• First Submitted: July 22, 2014
• First Posted: July 24, 2014
• Study Start: November 1, 2011
• Primary Completion: October 1, 2012
• Study Completion: October 1, 2012
• Last Updated: April 14, 2015

Record last verified: 2015-01

Locations

US (3)