Hepatic ImpairmentPhase 1NCT02421042
A Pharmacokinetic and Safety Study of E7080 in Subjects With Mild (10 mg), Moderate (10 mg), and Severe Hepatic Impairment (5 mg) and Normal Hepatic Function (10 mg)
A Phase 1 study testing Lenvatinib in people with Hepatic Impairment and Hepatic Function, run by Eisai Inc. at 5 sites in United States.
Trial summary
This is a multi-center, open-label, non-randomized, single-dose, sequential-cohort study in subjects with varying degrees of hepatic impairment, classified according to the Child-Pugh system, who will be matched with normal healthy subjects as controls. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatic Impairment, Hepatic Function
- What is being tested?
- Lenvatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 5 sitesUnited States
- Study dates
- Jun 2011to Jul 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- All subjects must meet all of the following criteria to be included in this study:
- Male or female subjects aged 18 to 70, inclusive
- BMI greater than or equal to 18 to lesser than or equal to 35 kg/m2, inclusive
- Non-smokers and smokers who smoke no more than 10 cigarettes per day
- All females must have a negative serum beta human chorionic gonadotropin (B-hCG) test result and a negative urine pregnancy test result at Screening and Baseline. Females of childbearing potential must agree to use a highly effective method of contraception (e.g., abstinence, an intrauterine device [IUD], a barrier method such as a condom plus spermicide or condom plus diaphragm with spermicide, a contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia) throughout the entire study period and for 30 days after study drug discontinuation. The only subjects who will be exempt from this requirement are postmenopausal females (defined as at least 12 months' consecutive amenorrhea, in the appropriate age group, without other known or suspected primary cause) or subjects who have been sterilized surgically or who are otherwise proven sterile (i.e., bilateral tubal ligation with surgery at least 1 month prior to dosing, hysterectomy, or bilateral oophorectomy with surgery at least 1 month prior to dosing). All women who are of reproductive potential and who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product for at least 4 weeks prior to dosing and must continue to use the same contraceptive during the study and for 30 days after study drug discontinuation.
- Male subjects who are not abstinent or have not undergone a successful vasectomy, who are partners of women of childbearing potential, must use, or their partners must use, a highly effective method of contraception (e.g., condom plus spermicide, condom plus diaphragm with spermicide, IUD) starting for at least one menstrual cycle prior to starting study drug(s) and throughout the entire study period and for 30 days (longer if appropriate) after the last dose of study drug.
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- Voluntarily provide written informed consent prior to any study procedures
- Are willing and able to comply with all aspects of the protocol for the duration of the study.
- Additionally, for subjects with hepatic impairment (based on the Child-Pugh classification system), the following key inclusion criteria will apply:
- Subjects must have a diagnosis of liver cirrhosis that has been stable, without any change in disease status, for 60 days prior to study screening, as determined by the investigator.
- Subjects must have a platelet count greater than 30,000 cells/mm3; if platelet count is lesser than 30,000 cells/mm3, the subject may be enrolled with joint approval of the principal investigator (PI) and medical monitor based on subject history and stability.
- Subjects must have no history of clinically relevant disease or condition (e.g., significant cardiac or renal dysfunction, diseases of the gastrointestinal tract or conditions which may impact drug absorption), as determined by the investigator.
- Subjects must have a total score on the Child-Pugh classification system between 5 and 6 (Group 1, mild impairment), 7 to 9 (Group 2, moderate impairment), and 10 to 15 (Group 3, severe impairment).
- Subjects with a history of Type I or Type II diabetes are permissible, providing that, in the opinion of the investigator, they have stable disease. Subjects receiving insulin therapy are permissible provided that they have been on a stable treatment for at least 2 weeks prior to study enrollment and continuing through the study.
Who cannot join
- All subjects who meet any of the following criteria will be excluded from participation in the study:
- Use of any new medication, including multi-vitamins, or an investigational drug within 14 days prior to the drug administration, or within five times the elimination half-life, whichever is longest, except combined oral contraceptives and occasional use of paracetamol or ibuprofen within 14 days and Vitamin K supplements and thiamine for hepatic impairment subjects; any local anesthetic within 3 days before study drug administration. Current over-the-counter (OTC) and prescription medication use is permitted, but must be stable and consistent for at least 14 days prior to screening and throughout the study treatment period.
- Positive human immunodeficiency virus (HIV) screening test
- QTc interval calculated by Fridericia's formula (QTcF) greater than 480 ms at screening or baseline
- Presence of acute active liver disease or acute liver injury as indicated by (1) an abnormal liver function test, or (2) clinical and/or laboratory signs of acute, active hepatitis A, B, and/or C. Subjects with stable, chronic, active hepatitis B or C may be enrolled if the investigator deems them to be appropriate.
- Additionally normal healthy subjects who meet any of the following criteria will be excluded from participation in the study:
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- Presence of clinically significant illness requiring treatment
- History of gastrointestinal surgery (cholecystectomy and appendectomy are, however, permitted)
- History of significant drug, food, or seasonal allergies
- Weight change during the Pretreatment Phase
- Significant findings revealed by the history, physical or clinical laboratory testing
- Alcohol misuse
- Caffeine intake within 72 hours of lenvatinib administration
- Participation in another clinical trial within 4 weeks of lenvatinib administration
- Receipt or donation of blood or blood products within 4 to 8 weeks of lenvatinib administration
- Engagement in strenuous exercise
- Unwillingness to abide by the study requirements, or, in the opinion of the investigator, unlikely to complete the study.
- Additionally subjects with hepatic impairment who meet any of the following criteria will be excluded from participation in the study:
- Subjects who have a history of hepatic transplant, systemic lupus erythematosus, or hepatic coma within 2 months prior to the Screening Period
- Subjects who are receiving or have received treatment with interferon or pegylated interferon within the past 60 days
- Subjects who have encephalopathy greater than Grade 2, sepsis, or gastrointestinal bleeding within 1 month before the Screening Period; esophageal varices greater than Grade 2, acute hepatic failure of any etiology, history of surgical portosystemic shunt, renal impairment (creatinine clearance lesser than 50 mL/min according to the Cockcroft-Gault formula), and rapidly deteriorating hepatic function indicated recently by clinical/laboratory signs of hepatic impairment within 2 months prior to the Screening Period.
- Subjects who have significant acute, new onset illness within 2 weeks prior to study drug administration
- In addition to the Key Exclusion Criteria above for all subjects, standard exclusion criteria for subjects with hepatic impairment in Phase 1 studies will be used. These include the presence of clinically significant illness requiring treatment where said illness is unrelated to their hepatitis, history of gastrointestinal surgery (cholecystectomy and appendectomy are, however, permitted); history of significant drug, food, or seasonal allergies; weight change during the PreTreatment Phase; significant findings revealed by the history, physical, or clinical laboratory testing where said findings are unrelated to the subject's hepatitis, alcohol misuse, or caffeine intake within 72 hours of E7080 administration; participation in another clinical trial within 4 weeks of lenvatinib administration; receipt or donation of blood or blood products within 4 to 8 weeks of lenvatinib administration; engagement in strenuous exercise; unwillingness to abide by the study requirements; or, in the opinion of the investigator, unlikely to complete the study.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Study site
Knoxville, Tennessee, 37920
Study site
Miami, Florida, 33014
Study site
Miami, Florida, 33169
Study site
Minneapolis, Minnesota, 55404
Study site
Orlando, Florida, 32809
About this study
This is a multi-center, open-label, non-randomized, single-dose, sequential-cohort study in subjects with varying degrees of hepatic impairment, classified according to the Child-Pugh system, who will be matched with normal healthy subjects as controls.
Read the detailed description
This is a multi-center, open-label, non-randomized, single-dose, sequential-cohort study in subjects with varying degrees of hepatic impairment, classified according to the Child-Pugh system, who will be matched with normal healthy subjects as controls. The study will be conducted in two phases: Pretreatment and Treatment. The Pretreatment Phase will have two periods: Screening and Baseline. The study will enroll a sufficient number of subjects so that at least 24 subjects complete the study. This will include six subjects with mild hepatic impairment (Group 1), six subjects with moderate hepatic impairment (Group 2), four to six subjects with severe hepatic impairment (Group 3), and eight subjects with normal hepatic function (Group 4). Potential study subjects with hepatic impairment (Groups 1, 2, and 3) and those with normal hepatic function (Group 4) will first be screened for study entry. Group 1, 2, and 3 subjects will be enrolled sequentially into the study first. The Group 4 normal healthy subjects will be enrolled following enrollment of all of the hepatic impairment subjects. Subjects determined to be eligible for the protocol will receive either a 5- or 10-mg single oral dose of lenvatinib on Day 1, depending on their hepatic status. Subjects will be discharged from the unit on Day 17 (+/- 2 days) after all study discharge procedures have been completed.
- Conditions
- Hepatic Impairment, Hepatic Function
- Being tested
- Lenvatinib
- Keywords
- Hepatic Impairment, Hepatic Function
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LenvatinibDrug
Also called E7080
5- or 10-mg single oral dose of E7080, depending on their hepatic status [Mild (10 mg), Moderate (10 mg), and Severe Hepatic Impairment (5 mg) and Normal Hepatic Function (10 mg)].
| Study group | Role | What they receive |
|---|---|---|
| Lenvatinib | Experimental | Subjects determined to be eligible for the protocol will receive either a 5- or 10-mg single oral dose of lenvatinib on Day 1, depending on their hepatic status [Mild (10 mg), Moderate (10 mg), and Severe Hepatic Impairment (5 mg) and Normal Hepatic Function (10 mg)]. Receives: Drug: Lenvatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics of lenvatinib: Cmax
Plasma concentrations of lenvatinib (free and total) and its metabolites, M1, M2, M3, and M5, (total) and urine concentrations of lenvatinib (total) and its metabolites, M1, M2, M3, and M5, (total) will be assessed.
Measured: 336 hours post study drug administration
Pharmacokinetics of lenvatinib: AUC(0-t)
Plasma concentrations of lenvatinib (free and total) and its metabolites, M1, M2, M3, and M5, (total) and urine concentrations of lenvatinib (total) and its metabolites, M1, M2, M3, and M5, (total) will be assessed.
Measured: 336 hours post study drug administration
Pharmacokinetics of lenvatinib: AUC(0-inf)
Plasma concentrations of lenvatinib (free and total) and its metabolites, M1, M2, M3, and M5, (total) and urine concentrations of lenvatinib (total) and its metabolites, M1, M2, M3, and M5, (total) will be assessed.
Measured: 336 hours post study drug administration
Safety of lenvatinib as assessed by Vital Signs
Measured: Screening, Baseline and Treatment [upto Study discharge (17 days plus or minus 2 days)]
Secondary outcomes (3)
Safety of lenvatinib as assessed by Adverse Events/Serious Adverse Events
Measured: Screening, Baseline and Treatment [upto Study discharge (17 days plus or minus 2 days)]
Safety of lenvatinib as assessed by Laboratory Values
Measured: Screening, Baseline and Treatment [upto Study discharge (17 days plus or minus 2 days)]
Safety of lenvatinib as assessed by ECGs
Measured: Screening, Baseline and Treatment [upto Study discharge (17 days plus or minus 2 days)]
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2015 (estimated)
- Study startJun 2011
- Primary completionJul 2012
- Study completionJul 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatic ImpairmentStudies of the same condition, open and under way.
- More trials run by Eisai Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eisai Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02421042
- Sponsor's protocol ID
- E7080-A001-006
- Status last verified
- May 2015
- First submitted
- 22 Jul 2014
- Last updated
- 5 May 2015
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pharmacokinetic and Safety Study of E7080 in Subjects With Mild (10 mg), Moderate (10 mg), and Severe Hepatic Impairment (5 mg) and Normal Hepatic Function (10 mg)
- ClinicalTrials.gov ID
- NCT02421042
- Acronym / sponsor ID
- E7080-A001-006
- Conditions
- Hepatic Impairment, Hepatic Function
- Keywords
- Hepatic Impairment, Hepatic Function
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Eisai Inc.Industry (pharma, biotech, devices)
- Study start
- Jun 2011
- Primary completion
- Jul 2012 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 20 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multi-center, open-label, non-randomized, single-dose, sequential-cohort study in subjects with varying degrees of hepatic impairment, classified according to the Child-Pugh system, who will be matched with normal healthy subjects as controls.
Detailed description
This is a multi-center, open-label, non-randomized, single-dose, sequential-cohort study in subjects with varying degrees of hepatic impairment, classified according to the Child-Pugh system, who will be matched with normal healthy subjects as controls. The study will be conducted in two phases: Pretreatment and Treatment. The Pretreatment Phase will have two periods: Screening and Baseline. The study will enroll a sufficient number of subjects so that at least 24 subjects complete the study. This will include six subjects with mild hepatic impairment (Group 1), six subjects with moderate hepatic impairment (Group 2), four to six subjects with severe hepatic impairment (Group 3), and eight subjects with normal hepatic function (Group 4). Potential study subjects with hepatic impairment (Groups 1, 2, and 3) and those with normal hepatic function (Group 4) will first be screened for study entry. Group 1, 2, and 3 subjects will be enrolled sequentially into the study first. The Group 4 normal healthy subjects will be enrolled following enrollment of all of the hepatic impairment subjects. Subjects determined to be eligible for the protocol will receive either a 5- or 10-mg single oral dose of lenvatinib on Day 1, depending on their hepatic status. Subjects will be discharged from the unit on Day 17 (+/- 2 days) after all study discharge procedures have been completed.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lenvatinib | Experimental | Drug: LenvatinibSubjects determined to be eligible for the protocol will receive either a 5- or 10-mg single oral dose of lenvatinib on Day 1, depending on their hepatic status [Mild (10 mg), Moderate (10 mg), and Severe Hepatic Impairment (5 mg) and Normal Hepatic Function (10 mg)]. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Male or female subjects aged 18 to 70, inclusive
- BMI greater than or equal to 18 to lesser than or equal to 35 kg/m2, inclusive
- Non-smokers and smokers who smoke no more than 10 cigarettes per day
- All females must have a negative serum beta human chorionic gonadotropin (B-hCG) test result and a negative urine pregnancy test result at Screening and Baseline. Females of childbearing potential must agree to use a highly effective method of contraception (e.g., abstinence, an intrauterine device [IUD], a barrier method such as a condom plus spermicide or condom plus diaphragm with spermicide, a contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia) throughout the entire study period and for 30 days after study drug discontinuation. The only subjects who will be exempt from this requirement are postmenopausal females (defined as at least 12 months' consecutive amenorrhea, in the appropriate age group, without other known or suspected primary cause) or subjects who have been sterilized surgically or who are otherwise proven sterile (i.e., bilateral tubal ligation with surgery at least 1 month prior to dosing, hysterectomy, or bilateral oophorectomy with surgery at least 1 month prior to dosing). All women who are of reproductive potential and who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product for at least 4 weeks prior to dosing and must continue to use the same contraceptive during the study and for 30 days after study drug discontinuation.
- Male subjects who are not abstinent or have not undergone a successful vasectomy, who are partners of women of childbearing potential, must use, or their partners must use, a highly effective method of contraception (e.g., condom plus spermicide, condom plus diaphragm with spermicide, IUD) starting for at least one menstrual cycle prior to starting study drug(s) and throughout the entire study period and for 30 days (longer if appropriate) after the last dose of study drug.
Key exclusion criteria (23 listed)
- All subjects who meet any of the following criteria will be excluded from participation in the study:
- Use of any new medication, including multi-vitamins, or an investigational drug within 14 days prior to the drug administration, or within five times the elimination half-life, whichever is longest, except combined oral contraceptives and occasional use of paracetamol or ibuprofen within 14 days and Vitamin K supplements and thiamine for hepatic impairment subjects; any local anesthetic within 3 days before study drug administration. Current over-the-counter (OTC) and prescription medication use is permitted, but must be stable and consistent for at least 14 days prior to screening and throughout the study treatment period.
- Positive human immunodeficiency virus (HIV) screening test
- QTc interval calculated by Fridericia's formula (QTcF) greater than 480 ms at screening or baseline
- Presence of acute active liver disease or acute liver injury as indicated by (1) an abnormal liver function test, or (2) clinical and/or laboratory signs of acute, active hepatitis A, B, and/or C. Subjects with stable, chronic, active hepatitis B or C may be enrolled if the investigator deems them to be appropriate.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LenvatinibAlso: E70805- or 10-mg single oral dose of E7080, depending on their hepatic status [Mild (10 mg), Moderate (10 mg), and Severe Hepatic Impairment (5 mg) and Normal Hepatic Function (10 mg)]. | Drug | Lenvatinib |
Primary outcome
Pharmacokinetics of lenvatinib: Cmax
Time frame: 336 hours post study drug administration
Plasma concentrations of lenvatinib (free and total) and its metabolites, M1, M2, M3, and M5, (total) and urine concentrations of lenvatinib (total) and its metabolites, M1, M2, M3, and M5, (total) will be assessed.
Pharmacokinetics of lenvatinib: AUC(0-t)
Time frame: 336 hours post study drug administration
Plasma concentrations of lenvatinib (free and total) and its metabolites, M1, M2, M3, and M5, (total) and urine concentrations of lenvatinib (total) and its metabolites, M1, M2, M3, and M5, (total) will be assessed.
Pharmacokinetics of lenvatinib: AUC(0-inf)
Time frame: 336 hours post study drug administration
Plasma concentrations of lenvatinib (free and total) and its metabolites, M1, M2, M3, and M5, (total) and urine concentrations of lenvatinib (total) and its metabolites, M1, M2, M3, and M5, (total) will be assessed.
Safety of lenvatinib as assessed by Vital Signs
Time frame: Screening, Baseline and Treatment [upto Study discharge (17 days plus or minus 2 days)]
3 secondary outcomes
Safety of lenvatinib as assessed by Adverse Events/Serious Adverse Events
Time frame: Screening, Baseline and Treatment [upto Study discharge (17 days plus or minus 2 days)]
Safety of lenvatinib as assessed by Laboratory Values
Time frame: Screening, Baseline and Treatment [upto Study discharge (17 days plus or minus 2 days)]
Safety of lenvatinib as assessed by ECGs
Time frame: Screening, Baseline and Treatment [upto Study discharge (17 days plus or minus 2 days)]
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Lenvatinib in people with Hepatic Impairment and Hepatic Function, run by Eisai Inc. at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacokinetics of lenvatinib: Cmax (time frame: 336 hours post study drug administration). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 May 2015.