Healthy VolunteersPhase 1NCT02198170
A Pharmacokinetic Study to Assess the Influence of Simultaneous CYP3A4 and P-glycoprotein Inhibition on E7080 Pharmacokinetics Following Single Dose Oral Administration of 5 mg E7080 to Healthy Volunteers
A Phase 1 study of Healthy Volunteers, run by Eisai Inc. at 1 site in United States.
Trial summary
The purpose of this study is to assess the influence of simultaneous CYP3A4 and p-glycoprotein inhibition on lenvatinib pharmacokinetics following a single oral dose of 5 mg lenvatinib. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2011to Jun 2011
- 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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Non-smoking (i.e., no use of nicotine or nicotine containing products within the past 3 months), male or female subjects, age greater than or equal to 18 years and less than or equal to 55 years
- Body mass index (BMI) greater than or equal to 18 and less than or equal to 30 kg/m2 at screening
- All females must have a negative serum and urine B-hCG test result at Screening and Baseline. Females of child-bearing potential must agree to use a medically acceptable method of contraception (e.g., abstinence; a highly effective method such as an intrauterine device [IUD], condom + spermicide or condom + diaphragm with spermicide, a contraceptive implant, an oral contraceptive; or have a vasectomized partner) 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 women (defined as greater than age 50 and at least 12 months of amenorrhea) or subjects who have been sterilized surgically or who are otherwise proven sterile (e.g., bilateral tubal ligation with surgery at least 6 months prior to dosing, hysterectomy, or bilateral oophorectomy with surgery at least 2 months 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 12 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 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 + spermicide, condom + diaphragm with spermicide, IUD) starting for at least one menstrual cycle prior to starting study drug(s) and throughout the entire study and for 30 days after the last dose of study drug. Those with partners using hormonal contraceptives must also be using an additional approved method of contraception (as described previously).
- Provide written informed consent
- Are willing and able to comply with all aspects of the protocol
Who cannot join
- Subjects who had a clinically significant illness that required medical treatment within 8 weeks or a clinically significant infection within 4 weeks of dosing
- Subjects with a disease that may influence the outcome of the study; such as psychiatric disorders and disorders of the gastrointestinal tract, liver, kidney, respiratory system, endocrine system, hematological system, neurological system, or cardiovascular system, or subjects who have a congenital abnormality in metabolism within 4 weeks prior to dosing
- Subjects with a history of gastrointestinal surgery (hepatectomy, nephrotomy, digestive organ resection, etc.) that may affect pharmacokinetic profiles of lenvatinib
- Subjects with a known history of clinically significant drug or food allergies or presently experiencing significant seasonal allergy
- Subjects who experienced a weight loss or gain of greater than 10% between screening and prior to dosing
- Subjects with any clinically abnormal symptom or organ impairment found on medical history, symptoms/signs, vital signs, ECG finding, or laboratory test results which require medical treatment
Show all 22Show fewer
- Subjects with a QTc interval greater than 450 ms at screening or check-in
- Subjects with hemoglobin level less than 12.0 g/dL
- Subjects who had a positive result from human immunodeficiency virus (HIV) or hepatitis C virus antibody (HCVAb) screening tests, or clinical evidence of active viral Hepatitis A or B
- Subjects with a known or suspected history of drug or alcohol misuse within 6 months prior to screening, or a positive urine drug or alcohol test at screening or baseline
- Subjects who have consumed caffeinated beverages within 72 hours prior to baseline
- Subjects who have taken dietary supplements, juice, or herbal preparations or other foods or beverages that may affect various drug metabolizing enzymes and transporters [e.g., alcohol, grapefruit, grapefruit juice, grapefruit-containing beverages, apple or orange juice), vegetables from the mustard green family (e.g., kale, broccoli, watercress, collard greens, kohlrabi, brussel sprouts, mustard), and charbroiled meats] within 2 weeks prior to dosing
- Subjects who have taken herbal preparations containing St. John's Wort within 4 weeks prior to dosing
- Subjects who have taken prescription drugs within 4 weeks prior to screening (however, use of prescription contraceptive products is permitted)
- Subjects who have taken over-the-counter (OTC) medications within 2 weeks prior to dosing
- Subjects who have participated in another clinical trial of an investigational drug or device within 4 weeks prior to dosing
- Subjects who have received blood products within 4 weeks, or donated blood within 8 weeks, or donated plasma within 1 week of dosing
- Subjects who have engaged in heavy exercise within 2 weeks prior to check-in (e.g., marathon runners, weight lifters, etc.)
- Subjects who are unwilling or unable to abide by the requirements of the study
- Subjects who have any condition that would make him/her, in the opinion of the investigator, unsuitable for the study or who, in the opinion of the investigator, are not likely to complete the study for any reason
- Known intolerance to the study drugs or any of the excipients
- Females who are either pregnant or lactating
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to assess the influence of simultaneous CYP3A4 and p-glycoprotein inhibition on lenvatinib pharmacokinetics following a single oral dose of 5 mg lenvatinib.
Read the detailed description
This is a single-center, randomized, open-label, two-period, crossover study consisting of two phases: Prerandomization and Randomization. The Prerandomization Phase will have two periods: Screening and Baseline 1. The Randomization Phase will have two periods: Treatment Period 1 and Treatment Period 2 with a Baseline 2 assessment prior to Treatment Period 2. In the Randomization Phase, subjects will be randomized to one of two possible treatment sequences (placebo/ketoconazole or ketoconazole/placebo). Ketoconazole 400 mg or placebo will be orally administered once daily for the first four days of each treatment period. On the fifth day of each treatment period, in addition to ketoconazole/placebo, 5 mg lenvatinib will be orally administered. Ketoconazole/placebo administration will then continue for 13 additional days. Subjects are crossed over from Treatment Period 1 to Treatment Period 2 after a 2-week washout.
- Conditions
- Healthy Volunteers
- Being tested
- ketoconazole-placebo, placebo-ketoconazole
- Keywords
- Healthy Volunteers
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ketoconazole-placeboDrug
Also called E7080
Treatment Period 1: 400 mg ketoconazole orally once daily + single oral dose of 5 mg lenvatinib on fifth day of 19-day treatment period. Treatment Period 2: Placebo orally once daily + single oral dose of 5 mg lenvatinib of fifth day on 19-day treatment period.
placebo-ketoconazoleDrug
Also called E7080
Treatment Period 1: Placebo orally once daily + single oral dose of 5 mg lenvatinib on fifth day of 19-day treatment period Treatment Period 2: 400 mg ketoconazole orally once daily + single oral dose of 5 mg lenvatinib on fifth day of 19-day treatment period
| Study group | Role | What they receive |
|---|---|---|
| ketoconazole-placebo | Experimental | Treatment Period 1: 400 mg ketoconazole orally once daily + single oral dose of 5 mg lenvatinib on fifth day of 19-day treatment period Treatment Period 2: Placebo orally once daily + single oral dose of 5 mg lenvatinib of fifth day on 19-day treatment period Receives: Drug: ketoconazole-placebo |
| placebo-ketoconazole | Experimental | Treatment Period 1: Placebo orally once daily + single oral dose of 5 mg lenvatinib on fifth day of 19-day treatment period Treatment Period 2: 400 mg ketoconazole orally once daily + single oral dose of 5 mg lenvatinib on fifth day of 19-day treatment period Receives: Drug: placebo-ketoconazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics of CYP3A4 and p-glycoprotein inhibition on lenvatinib: Cmax
Measured: Baseline 1 (Day -1) and 2 (Day 33); Treatment period 1 and 2: Predose and at 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48, 72, 96, 120, 144, 168, 240, 288, and 336 hours post dose
Pharmacokinetics of CYP3A4 and p-glycoprotein inhibition on lenvatinib: AUC(0-t)
Measured: Baseline 1 (Day -1) and 2 (Day 33); Treatment period 1 and 2: Predose and at 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48, 72, 96, 120, 144, 168, 240, 288, and 336 hours post dose
Pharmacokinetics of CYP3A4 and p-glycoprotein inhibition on lenvatinib: AUC(0-inf)
Measured: Baseline 1 (Day -1) and 2 (Day 33); Treatment period 1 and 2: Predose and at 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48, 72, 96, 120, 144, 168, 240, 288, and 336 hours post dose
Secondary outcomes (5)
Safety as Measured by Outcome of Adverse Events
Measured: Screening, Up to Day 52
Safety as Measured by Laboratory Values
Measured: Screening, Up to Day 52
Safety as Measured by Vital Signs
Measured: Screening, Up to Day 52
Safety as Measured by ECGs
Measured: Screening, Up to Day 52
Safety as Measured by Physical Examination
Measured: Screening, Up to Day 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2014 (estimated)
- Study startFeb 2011
- Primary completionJun 2011
- Study completionJun 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy VolunteersStudies 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
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 18 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
- NCT02198170
- Sponsor's protocol ID
- E7080-A001-004
- Status last verified
- Jan 2015
- First submitted
- 21 Jul 2014
- Last updated
- 13 Feb 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pharmacokinetic Study to Assess the Influence of Simultaneous CYP3A4 and P-glycoprotein Inhibition on E7080 Pharmacokinetics Following Single Dose Oral Administration of 5 mg E7080 to Healthy Volunteers
- ClinicalTrials.gov ID
- NCT02198170
- Acronym / sponsor ID
- E7080-A001-004
- Conditions
- Healthy Volunteers
- Keywords
- Healthy Volunteers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Eisai Inc.Industry (pharma, biotech, devices)
- Study start
- Feb 2011
- Primary completion
- Jun 2011 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 23 Jul 2014 (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.
The purpose of this study is to assess the influence of simultaneous CYP3A4 and p-glycoprotein inhibition on lenvatinib pharmacokinetics following a single oral dose of 5 mg lenvatinib.
Detailed description
This is a single-center, randomized, open-label, two-period, crossover study consisting of two phases: Prerandomization and Randomization. The Prerandomization Phase will have two periods: Screening and Baseline 1. The Randomization Phase will have two periods: Treatment Period 1 and Treatment Period 2 with a Baseline 2 assessment prior to Treatment Period 2. In the Randomization Phase, subjects will be randomized to one of two possible treatment sequences (placebo/ketoconazole or ketoconazole/placebo). Ketoconazole 400 mg or placebo will be orally administered once daily for the first four days of each treatment period. On the fifth day of each treatment period, in addition to ketoconazole/placebo, 5 mg lenvatinib will be orally administered. Ketoconazole/placebo administration will then continue for 13 additional days. Subjects are crossed over from Treatment Period 1 to Treatment Period 2 after a 2-week washout.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ketoconazole-placebo | Experimental | Drug: ketoconazole-placeboTreatment Period 1: 400 mg ketoconazole orally once daily + single oral dose of 5 mg lenvatinib on fifth day of 19-day treatment period Treatment Period 2: Placebo orally once daily + single oral dose of 5 mg lenvatinib of fifth day on 19-day treatment period |
| placebo-ketoconazole | Experimental | Drug: placebo-ketoconazoleTreatment Period 1: Placebo orally once daily + single oral dose of 5 mg lenvatinib on fifth day of 19-day treatment period Treatment Period 2: 400 mg ketoconazole orally once daily + single oral dose of 5 mg lenvatinib on fifth day of 19-day treatment period |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Non-smoking (i.e., no use of nicotine or nicotine containing products within the past 3 months), male or female subjects, age greater than or equal to 18 years and less than or equal to 55 years
- Body mass index (BMI) greater than or equal to 18 and less than or equal to 30 kg/m2 at screening
- All females must have a negative serum and urine B-hCG test result at Screening and Baseline. Females of child-bearing potential must agree to use a medically acceptable method of contraception (e.g., abstinence; a highly effective method such as an intrauterine device [IUD], condom + spermicide or condom + diaphragm with spermicide, a contraceptive implant, an oral contraceptive; or have a vasectomized partner) 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 women (defined as greater than age 50 and at least 12 months of amenorrhea) or subjects who have been sterilized surgically or who are otherwise proven sterile (e.g., bilateral tubal ligation with surgery at least 6 months prior to dosing, hysterectomy, or bilateral oophorectomy with surgery at least 2 months 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 12 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 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 + spermicide, condom + diaphragm with spermicide, IUD) starting for at least one menstrual cycle prior to starting study drug(s) and throughout the entire study and for 30 days after the last dose of study drug. Those with partners using hormonal contraceptives must also be using an additional approved method of contraception (as described previously).
- Provide written informed consent
Key exclusion criteria (22 listed)
- Subjects who had a clinically significant illness that required medical treatment within 8 weeks or a clinically significant infection within 4 weeks of dosing
- Subjects with a disease that may influence the outcome of the study; such as psychiatric disorders and disorders of the gastrointestinal tract, liver, kidney, respiratory system, endocrine system, hematological system, neurological system, or cardiovascular system, or subjects who have a congenital abnormality in metabolism within 4 weeks prior to dosing
- Subjects with a history of gastrointestinal surgery (hepatectomy, nephrotomy, digestive organ resection, etc.) that may affect pharmacokinetic profiles of lenvatinib
- Subjects with a known history of clinically significant drug or food allergies or presently experiencing significant seasonal allergy
- Subjects who experienced a weight loss or gain of greater than 10% between screening and prior to dosing
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 |
|---|---|---|
| ketoconazole-placeboAlso: E7080Treatment Period 1: 400 mg ketoconazole orally once daily + single oral dose of 5 mg lenvatinib on fifth day of 19-day treatment period. Treatment Period 2: Placebo orally once daily + single oral dose of 5 mg lenvatinib of fifth day on 19-day treatment period. | Drug | ketoconazole-placebo |
| placebo-ketoconazoleAlso: E7080Treatment Period 1: Placebo orally once daily + single oral dose of 5 mg lenvatinib on fifth day of 19-day treatment period Treatment Period 2: 400 mg ketoconazole orally once daily + single oral dose of 5 mg lenvatinib on fifth day of 19-day treatment period | Drug | placebo-ketoconazole |
Primary outcome
Pharmacokinetics of CYP3A4 and p-glycoprotein inhibition on lenvatinib: Cmax
Time frame: Baseline 1 (Day -1) and 2 (Day 33); Treatment period 1 and 2: Predose and at 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48, 72, 96, 120, 144, 168, 240, 288, and 336 hours post dose
Pharmacokinetics of CYP3A4 and p-glycoprotein inhibition on lenvatinib: AUC(0-t)
Time frame: Baseline 1 (Day -1) and 2 (Day 33); Treatment period 1 and 2: Predose and at 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48, 72, 96, 120, 144, 168, 240, 288, and 336 hours post dose
Pharmacokinetics of CYP3A4 and p-glycoprotein inhibition on lenvatinib: AUC(0-inf)
Time frame: Baseline 1 (Day -1) and 2 (Day 33); Treatment period 1 and 2: Predose and at 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48, 72, 96, 120, 144, 168, 240, 288, and 336 hours post dose
5 secondary outcomes
Safety as Measured by Outcome of Adverse Events
Time frame: Screening, Up to Day 52
Safety as Measured by Laboratory Values
Time frame: Screening, Up to Day 52
Safety as Measured by Vital Signs
Time frame: Screening, Up to Day 52
Safety as Measured by ECGs
Time frame: Screening, Up to Day 52
Safety as Measured by Physical Examination
Time frame: Screening, Up to Day 52
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 13 Feb 2015.
Related trials for Healthy Volunteers
Not yet recruiting
Neuroergonomic Analysis of a Brain-Computer Interface Device (BCI)
Healthy Volunteers - Male and Female
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis
Not yet recruitingObservational study
Establishment of Biobank of Nasal Epithelium Samples From Healthy Volunteers
Healthy
RecruitingObservational study
Improved Methods of Cell Selection for Bone Marrow Transplant Alternatives
Graft-Versus-Host Disease, Graft-versus-leukemia
Not yet recruitingObservational study
Screening Protocol
Pain
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study of Healthy Volunteers, run by Eisai Inc. at 1 site 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 6 inclusion and 22 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 13 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 CYP3A4 and p-glycoprotein inhibition on lenvatinib: Cmax (time frame: Baseline 1 (Day -1) and 2 (Day 33); Treatment period 1 and 2: Predose and at 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48, 72, 96, 120, 144, 168, 240, 288, and 336 hours post dose). The study lists 3 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 13 Feb 2015.