Phase 0 Study in Healthy, Hepatic and Renal Impaired Subjects to Obtain Plasma for Lenvatinib Protein Binding
- Conditions
- Hepatic Impairment; Renal Impairment
- Interventions
- Drug: Plasma Sampling
- Registration Number
- NCT02998775
- Lead Sponsor
- Eisai Inc.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 54
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
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 6 participants with mild hepatic impairment Plasma Sampling Hepatic impairment mild: total score on the Child-Pugh classification system between 5 and 6 6 participants with moderate renal impairment Plasma Sampling Renal Impairment Moderate: creatinine clearance, 30 to 49 mL/min 6 participants with mild renal impairment Plasma Sampling Renal Impairment Mild: creatinine clearance, 50 to 80 milliliters per minute (mL/min) 6 participants with severe renal impairment Plasma Sampling Renal Impairment Severe: creatinine clearance, 15 to 29 mL/min 8 participants normal renal status Plasma Sampling Renal status normal as defined by creatinine clearance ≥ 81 mL/min, otherwise age, gender, and smoking characteristics matching renal-impaired participants 6 participants with moderate hepatic impairment Plasma Sampling Hepatic impairment moderate: total score on the Child-Pugh classification system between 7 and 9 8 participants normal hepatic status Plasma Sampling Hepatic status normal, otherwise age, gender, and smoking characteristics matching hepatic-impaired participants 6 participants with severe hepatic impairment Plasma Sampling Hepatic impairment severe: total score on the Child-Pugh classification system between 10 and 15
- Primary Outcome Measures
Name Time Method Number of participants with any serious adverse event and any non-serious adverse event 1 week
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (3)
New Orleans Center for Clinical Research
🇺🇸Knoxville, Tennessee, United States
Orlando Clinical Research Center, Inc.
🇺🇸Orlando, Florida, United States
DaVita Clinical Research
🇺🇸Minneapolis, Minnesota, United States