Clinical trial NCT02998775: Phase 0 Study in Healthy, Hepatic and Renal Impaired Subjects to Obtain Plasma for Lenvatinib Protein Binding
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Hepatic Impairment; Renal Impairment
Keywords: in vitro protein binding
hepatic impairment
renal impairment
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2016-12-20
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with any serious adverse event and any non-serious adverse event
timeFrame: 1 week
Secondary outcomes:
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Orlando Clinical Research Center, Inc.
state: Florida
city: Minneapolis
country: United States
facility: DaVita Clinical Research
state: Minnesota
city: Knoxville
country: United States
facility: New Orleans Center for Clinical Research
state: Tennessee
Study officials:
References: