Phase 0 Study in Healthy, Hepatic and Renal Impaired Subjects to Obtain Plasma for Lenvatinib Protein Binding

A Multicenter Phase 0 Study In Healthy Subjects and Subjects With Either Hepatic Or Renal Impairment To Obtain Plasma For Assessment In Vitro Lenvatinib Protein Binding

E7080-A001-010 is a multicenter, parallel-group study in participants with mild, moderate, or severe hepatic or renal impairment and age-, gender-, and smoking status-matched healthy participants. The primary objective of the study is to obtain plasma from participants for use in in vitro protein binding studies.

Study Overview

• Status: Completed
• Conditions: Hepatic Impairment; Renal Impairment
• Intervention / Treatment: Drug: Plasma Sampling

Detailed Description

E7080-A001-010 is a multicenter, parallel-group study in participants with mild, moderate, or severe hepatic or renal impairment and age-, gender-, and smoking status-matched healthy participants. Approximately 6 participants with each degree (mild, moderate, or severe) of hepatic or renal impairment will be enrolled. Two cohorts of 8 healthy participants will be enrolled. One cohort of healthy participants will be matched to the hepatic-impaired participants, whereas the other will be matched to the renal-impaired participants.

The study has 2 phases. The Pre-study Phase consists of a Screening Period and a Baseline Period. The Study Phase consists of a 2-day Study Period. No lenvatinib will be administered in this study.

The end of the study will be the date of the last study visit for the last participant in the study.

The following estimates are provided:

• From first participant in to last participant out, the study is expected to take approximately one year to complete.
• The maximum estimated duration of the study for each participant is anticipated to be approximately 5 weeks.

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States
      • Orlando Clinical Research Center, Inc.
  • Minnesota
    • Minneapolis, Minnesota, United States
      • DaVita Clinical Research
  • Tennessee
    • Knoxville, Tennessee, United States
      • New Orleans Center for Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Key Inclusion Criteria:

• Male or Female

• Age, at the time of Informed Consent:

  i. Hepatic Impairment Participants (Including Matched Healthy Participants): 18 to 70 years old, inclusive ii. Renal Impairment Participants (Including Matched Healthy Participants): 18 to 79 years old, inclusive

• Non-smokers and smokers who smoke no more than 10 cigarettes per day
• Besides diabetes and, as appropriate, renal or hepatic impairment, participants must have no history of acute or chronic clinically relevant disease or condition, as determined by the investigator.

• For participants with hepatic impairment:

  • Liver cirrhosis that has been stable;
  • Platelet count >30,000 cells/millimeter cubed (mm^3);
  • Total score on the Child-Pugh classification system between 5 and 6 (Group 1, mild), 7 and 9 (Group 2, moderate), and 10 and 15 (Group 3, severe)

• For healthy participants:

  • Creatinine clearance ≥ 81 milliliter per minute (mL/min)

• For participants with renal impairment:

  • Must have a diagnosis of renal impairment that has been stable
  • Must have renal impairment in the following categories based on creatinine clearance values: mild (creatinine clearance, 50 to 80 mL/min), moderate (creatinine clearance, 30 to 49 mL/min), or severe (creatinine clearance, 15 to 29 mL/min) renal impairment

Exclusion Criteria:

Key Exclusion Criteria:

• Use of any new medication
• Human immunodeficiency virus (HIV) positive
• Presence of acute active liver disease or acute liver injury
• History of significant cardiovascular impairment
• Positive drug or alcohol test
• Weight loss or gain of >10% prior to Day 1
• Receipt of blood or blood products or donation of blood or blood products

For participants with hepatic impairment:

• History of hepatic transplant, systemic lupus erythematosus, or hepatic coma
• Received treatment with interferon or pegylated interferon
• Participants who have encephalopathy >Grade 2, sepsis, or gastrointestinal bleeding; esophageal varices >Grade 2, acute hepatic failure of any etiology, history of surgical portosystemic shunt, renal impairment (creatinine clearance <50 mL/min according to the Cockcroft-Gault formula), and rapidly deteriorating hepatic function
• Systolic blood pressure (SBP) ≥ 160 millimeters of mercury (mmHg) and/or diastolic blood pressure (DBP) ≥ 100 mmHg

For healthy participants:

• Hemoglobin level less than 12.0 grams per deciliter (g/dL)

For participants with renal impairment:

• A history of renal transplant
• SBP ≥ 160 mmHg and/or DBP ≥ 100 mmHg for participants with mild renal impairment; SBP ≥ 180 mmHg and/or DBP ≥ 110 mmHg for participants with moderate and severe renal impairment
• Significant bleeding diathesis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 6 participants with mild renal impairment; Renal Impairment Mild: creatinine clearance, 50 to 80 milliliters per minute (mL/min)	Drug: Plasma Sampling; No lenvatinib will be administered in this study; however, plasma samples will be obtained for assessment of in vitro lenvatinib protein binding.
Other: 6 participants with moderate renal impairment; Renal Impairment Moderate: creatinine clearance, 30 to 49 mL/min	Drug: Plasma Sampling; No lenvatinib will be administered in this study; however, plasma samples will be obtained for assessment of in vitro lenvatinib protein binding.
Other: 6 participants with severe renal impairment; Renal Impairment Severe: creatinine clearance, 15 to 29 mL/min	Drug: Plasma Sampling; No lenvatinib will be administered in this study; however, plasma samples will be obtained for assessment of in vitro lenvatinib protein binding.
Other: 8 participants normal renal status; Renal status normal as defined by creatinine clearance ≥ 81 mL/min, otherwise age, gender, and smoking characteristics matching renal-impaired participants	Drug: Plasma Sampling; No lenvatinib will be administered in this study; however, plasma samples will be obtained for assessment of in vitro lenvatinib protein binding.
Other: 6 participants with mild hepatic impairment; Hepatic impairment mild: total score on the Child-Pugh classification system between 5 and 6	Drug: Plasma Sampling; No lenvatinib will be administered in this study; however, plasma samples will be obtained for assessment of in vitro lenvatinib protein binding.
Other: 6 participants with moderate hepatic impairment; Hepatic impairment moderate: total score on the Child-Pugh classification system between 7 and 9	Drug: Plasma Sampling; No lenvatinib will be administered in this study; however, plasma samples will be obtained for assessment of in vitro lenvatinib protein binding.
Other: 6 participants with severe hepatic impairment; Hepatic impairment severe: total score on the Child-Pugh classification system between 10 and 15	Drug: Plasma Sampling; No lenvatinib will be administered in this study; however, plasma samples will be obtained for assessment of in vitro lenvatinib protein binding.
Other: 8 participants normal hepatic status; Hepatic status normal, otherwise age, gender, and smoking characteristics matching hepatic-impaired participants	Drug: Plasma Sampling; No lenvatinib will be administered in this study; however, plasma samples will be obtained for assessment of in vitro lenvatinib protein binding.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with any serious adverse event and any non-serious adverse event	1 week

Collaborators and Investigators

• Sponsor: Eisai Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2016
• Primary Completion (Actual): July 8, 2017
• Study Completion (Actual): July 8, 2017

Study Registration Dates

• First Submitted: December 16, 2016
• First Submitted That Met QC Criteria: December 19, 2016
• First Posted (Estimate): December 20, 2016

Study Record Updates

• Last Update Posted (Actual): September 7, 2018
• Last Update Submitted That Met QC Criteria: September 6, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: renal impairment; hepatic impairment; in vitro protein binding
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency
• Other Study ID Numbers: E7080-A001-010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO