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

NCT02998775 | Completed Early Phase 1

• 1 other identifier: E7080-A001-010
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Hepatic Impairment; Renal Impairment

Keywords

in vitro protein binding; hepatic impairment; renal impairment

Outcome Measures

Primary Outcomes (1)

• Number of participants with any serious adverse event and any non-serious adverse event

  1 week

Study Arms (8)

6 participants with mild renal impairment

OTHER

Renal Impairment Mild: creatinine clearance, 50 to 80 milliliters per minute (mL/min)

Drug: Plasma Sampling

6 participants with moderate renal impairment

OTHER

Renal Impairment Moderate: creatinine clearance, 30 to 49 mL/min

Drug: Plasma Sampling

6 participants with severe renal impairment

OTHER

Renal Impairment Severe: creatinine clearance, 15 to 29 mL/min

Drug: Plasma Sampling

8 participants normal renal status

OTHER

Renal status normal as defined by creatinine clearance ≥ 81 mL/min, otherwise age, gender, and smoking characteristics matching renal-impaired participants

Drug: Plasma Sampling

6 participants with mild hepatic impairment

OTHER

Hepatic impairment mild: total score on the Child-Pugh classification system between 5 and 6

Drug: Plasma Sampling

6 participants with moderate hepatic impairment

OTHER

Hepatic impairment moderate: total score on the Child-Pugh classification system between 7 and 9

Drug: Plasma Sampling

6 participants with severe hepatic impairment

OTHER

Hepatic impairment severe: total score on the Child-Pugh classification system between 10 and 15

Drug: Plasma Sampling

8 participants normal hepatic status

OTHER

Hepatic status normal, otherwise age, gender, and smoking characteristics matching hepatic-impaired participants

Drug: Plasma Sampling

Interventions

Plasma Sampling DRUG

No lenvatinib will be administered in this study; however, plasma samples will be obtained for assessment of in vitro lenvatinib protein binding.

6 participants with mild hepatic impairment; 6 participants with mild renal impairment; 6 participants with moderate hepatic impairment; 6 participants with moderate renal impairment; 6 participants with severe hepatic impairment; 6 participants with severe renal impairment; 8 participants normal hepatic status; 8 participants normal renal status

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (3)

Orlando Clinical Research Center, Inc.

Orlando, Florida, United States

Location

DaVita Clinical Research

Minneapolis, Minnesota, United States

Location

New Orleans Center for Clinical Research

Knoxville, Tennessee, United States

Location

MeSH Terms

Conditions

Renal Insufficiency

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: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2016
• First Posted: December 20, 2016
• Study Start: December 2, 2016
• Primary Completion: July 8, 2017
• Study Completion: July 8, 2017
• Last Updated: September 7, 2018

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)