Back to resultsPhase 0 Study in Healthy, Hepatic and Renal Impaired Subjects to Obtain Plasma for Lenvatinib Protein Binding
Primary Purpose
Hepatic Impairment; Renal Impairment
Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Plasma Sampling
Sponsored by
About this trial
This is an interventional basic science trial for Hepatic Impairment; Renal Impairment focused on measuring in vitro protein binding, hepatic impairment, renal impairment
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
Sites / Locations
- Orlando Clinical Research Center, Inc.
- DaVita Clinical Research
- New Orleans Center for Clinical Research
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm Type
Other
Other
Other
Other
Other
Other
Other
Other
Arm Label
6 participants with mild renal impairment
6 participants with moderate renal impairment
6 participants with severe renal impairment
8 participants normal renal status
6 participants with mild hepatic impairment
6 participants with moderate hepatic impairment
6 participants with severe hepatic impairment
8 participants normal hepatic status
Arm Description
Renal Impairment Mild: creatinine clearance, 50 to 80 milliliters per minute (mL/min)
Renal Impairment Moderate: creatinine clearance, 30 to 49 mL/min
Renal Impairment Severe: creatinine clearance, 15 to 29 mL/min
Renal status normal as defined by creatinine clearance ≥ 81 mL/min, otherwise age, gender, and smoking characteristics matching renal-impaired participants
Hepatic impairment mild: total score on the Child-Pugh classification system between 5 and 6
Hepatic impairment moderate: total score on the Child-Pugh classification system between 7 and 9
Hepatic impairment severe: total score on the Child-Pugh classification system between 10 and 15
Hepatic status normal, otherwise age, gender, and smoking characteristics matching hepatic-impaired participants
Outcomes
Primary Outcome Measures
Number of participants with any serious adverse event and any non-serious adverse event
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02998775
Brief Title
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
2. Study Status
Record Verification Date
September 2018
Overall Recruitment Status
Completed
Study Start Date
December 2, 2016 (Actual)
Primary Completion Date
July 8, 2017 (Actual)
Study Completion Date
July 8, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eisai Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatic Impairment; Renal Impairment
Keywords
in vitro protein binding, hepatic impairment, renal impairment
7. Study Design
Primary Purpose
Basic Science
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
54 (Actual)
8. Arms, Groups, and Interventions
Arm Title
6 participants with mild renal impairment
Arm Type
Other
Arm Description
Renal Impairment Mild: creatinine clearance, 50 to 80 milliliters per minute (mL/min)
Arm Title
6 participants with moderate renal impairment
Arm Type
Other
Arm Description
Renal Impairment Moderate: creatinine clearance, 30 to 49 mL/min
Arm Title
6 participants with severe renal impairment
Arm Type
Other
Arm Description
Renal Impairment Severe: creatinine clearance, 15 to 29 mL/min
Arm Title
8 participants normal renal status
Arm Type
Other
Arm Description
Renal status normal as defined by creatinine clearance ≥ 81 mL/min, otherwise age, gender, and smoking characteristics matching renal-impaired participants
Arm Title
6 participants with mild hepatic impairment
Arm Type
Other
Arm Description
Hepatic impairment mild: total score on the Child-Pugh classification system between 5 and 6
Arm Title
6 participants with moderate hepatic impairment
Arm Type
Other
Arm Description
Hepatic impairment moderate: total score on the Child-Pugh classification system between 7 and 9
Arm Title
6 participants with severe hepatic impairment
Arm Type
Other
Arm Description
Hepatic impairment severe: total score on the Child-Pugh classification system between 10 and 15
Arm Title
8 participants normal hepatic status
Arm Type
Other
Arm Description
Hepatic status normal, otherwise age, gender, and smoking characteristics matching hepatic-impaired participants
Intervention Type
Drug
Intervention Name(s)
Plasma Sampling
Intervention Description
No lenvatinib will be administered in this study; however, plasma samples will be obtained for assessment of in vitro lenvatinib protein binding.
Primary Outcome Measure Information:
Title
Number of participants with any serious adverse event and any non-serious adverse event
Time Frame
1 week
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Facility Information:
Facility Name
Orlando Clinical Research Center, Inc.
City
Orlando
State/Province
Florida
Country
United States
Facility Name
DaVita Clinical Research
City
Minneapolis
State/Province
Minnesota
Country
United States
Facility Name
New Orleans Center for Clinical Research
City
Knoxville
State/Province
Tennessee
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Phase 0 Study in Healthy, Hepatic and Renal Impaired Subjects to Obtain Plasma for Lenvatinib Protein Binding
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