Healthy VolunteersPhase 1NCT02792829

Crossover Study to Evaluate the Relative Bioavailability and Palatability of a Lenvatinib Suspension Compared to the Capsule Formulation in Adult Healthy Volunteers

A Phase 1 study testing Lenvatinib in people with Healthy Volunteers, run by Eisai Inc. at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Healthy Volunteers
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: 60 participants
Where: 1 siteUnited States
Study dates: Aug 2014to Aug 2014
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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

Healthy male and female participants age greater than or equal to 18 years and less than or equal to 55 years old at time of informed consent
Nonsmokers or smokers who smoke no more than 10 cigarettes per day
BMI greater than or equal to 18 and less than or equal to 32 kg/m2 at screening
Adequate liver function, defined as: bilirubin less than or equal to 1.5 X the upper limit of normal (ULN), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and alanine aminotransferase (ALT) less than or equal to 1.5 X ULN
Adequate renal function defined as creatinine clearance greater than 70 mL/min calculated using the Cockcroft and Gault formula
Females must not be lactating or pregnant at Screening or Baseline (as documented by a negative beta-human chorionic gonadotropin [B-hCG] test with a minimum sensitivity of 25 IU/L, or equivalent units of B-hCG. A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.

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All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (ie, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing)
Females of childbearing potential must not have had unprotected sexual intercourse within 30 days before study entry and must agree to use a highly effective method of contraception (eg, total abstinence, an intrauterine device, a double-barrier method [such as 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. If currently abstinent, the participant must agree to use a double-barrier method as described above if she becomes sexually active during the study period or for 30 days after study drug discontinuation. Females who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product for at least 4 weeks before dosing and must continue to use the same contraceptive during the study and for 30 days after study drug discontinuation.
Male participants must have had a successful vasectomy (confirmed azoospermia), or they and their female partners must meet the criteria above (ie, not of childbearing potential or practicing highly effective contraception throughout the study period and for 30 days after study drug discontinuation). No sperm donation is allowed during the study period and for 30 days after study drug discontinuation.
Provide written informed consent
Willing and able to comply with all aspects of the protocol

Who cannot join

Clinically significant illness that requires medical treatment within 8 weeks prior, or a clinically significant infection that requires medical treatment within 4 weeks prior to dosing
Evidence of disease that may influence the outcome of the study, within 4 weeks prior to dosing; eg, psychiatric disorders and disorders of the gastrointestinal (GI) tract, liver, kidney, respiratory system, endocrine system, hematological system, neurological system, or cardiovascular system, or participants who have a congenital abnormality in metabolism
Any history of surgery that may affect PK profiles of lenvatinib eg, hepatectomy, nephrotomy, digestive organ resection, at screening or baseline
Any clinically abnormal symptom or organ impairment found by medical history, physical examinations, vital signs, electrocardiogram (ECG) finding, or laboratory test results that requires medical treatment at screening or baseline
Prolonged QTcF interval (QTcF greater than 450 ms) demonstrated on ECG at screening or baseline
Known history of clinically significant drug allergy at Screening or Baseline

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Known history of food allergies or presently experiencing significant seasonal or perennial allergy at Screening or Baseline
Known history of sensitivity to any of the components of the test products
Known to be human immunodeficiency virus (HIV) positive at screening
Active viral hepatitis (A, B, or C) as demonstrated by positive serology at screening
History of drug or alcohol dependency or abuse within the 2 years prior to screening, or those who have a positive urine drug test or breath alcohol test at Screening or Baseline
Engagement in strenuous exercise within 2 weeks prior to check-in (eg, marathon runners, weight lifters)
Any medical or other condition that would make the participant in the opinion of the investigator or sponsor, unsuitable for the study or who, in the opinion of the investigator, are not likely to complete the study for any reason
Intake of herbal preparations containing St. John's Wort within 4 weeks prior to dosing
Use of prescription drugs within 4 weeks prior to dosing
Intake of over-the-counter (OTC) medications within 2 weeks prior to dosing
Receipt of blood products within 4 weeks, or donation of blood within 8 weeks, or donation of plasma within 1 week prior to dosing

Trial locations and contacts

1 site in 1 country.

United States1 site

Study site
Las Vegas, Nevada

Other trials in United States

About this study

Official title: A Randomized Three-Arm, Single-dose, Two-period Crossover Study to Evaluate the Relative Bioavailability and Palatability of a Lenvatinib Suspension Compared to the Capsule Formulation in Adult Healthy Volunteers

The study will be conducted in adult healthy participants and will consist of two phases: Prerandomization and Randomization. The Prerandomization Phase will consist of 2 periods: a Screening Period and a Baseline Period. The Randomization Phase will consist of 2 Periods (each 6 days long) separated by a 1-day long Baseline Period and End of Treatment (EOT) Period. A total of 60 participants will be enrolled into one of three arms. Arms 1 and 3 consist of 2 sequences, and Arm 2 consists of 4 sequences (as this is an incomplete block design with 2 factors [number of capsules and whether water or apple juice is used as vehicle]). Each participant will be randomized into one of 8 sequences.

Conditions: Healthy Volunteers
Being tested: Lenvatinib
Keywords: Bioavailability of Lenvatinib suspension, Palatability of Lenvatinib suspension, Lenvatinib, Lenvima, E7080, Capsule formulation, Healthy volunteers

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LenvatinibDrug
Also called Lenvima; E7080
All participants will receive one single dose in each of the 2 treatment periods (total of 2 doses). The total duration of the treatment periods is 12 days (6 days per period) in healthy adult volunteers.

Study groups in NCT02792829
Study group	Role	What they receive
Lenvatinib 11 mg (suspension formulation)	Experimental	Arm 1 will have 2 sequences: 1. Sequence 1 - Treatment Period 1: 11 mg suspension (2 capsules, 1 x 10 mg and 1 x 1 mg); Treatment Period 2: 11 mg capsules (2 capsules, 1 x 10 mg and 1 x 1 mg) 2. Sequence 2 - Treatment Period 1: 11 mg capsules (2 capsules, 1 x 10 mg and 1 x 1 mg); Treatment Period 2: 11 mg suspension (2 capsules, 1 x 10 mg and 1 x 1 mg) Receives: Drug: Lenvatinib
Lenvatinib 11 mg (2 vs 5 capsules)	Experimental	Arm 2 will have 4 sequences: 1. Sequence 3 - Treatment Period 1: 11 mg suspension (5 capsules, 2 x 4 mg and 3 x 1 mg) WATER; Treatment Period 2: 11 mg suspension (2 capsules, 1 x 10 mg and 1 x 1 mg) APPLE JUICE 2. Sequence 4 - Treatment Period 1: 11 mg suspension (5 capsules, 2 x 4 mg and 3 x 1 mg capsules) APPLE JUICE; Treatment Period 2: 11 mg suspension (2 capsules, 1 x 10 mg and 1 x 1 mg capsules) WATER 3. Sequence 5 - Treatment Period 1: 11 mg suspension (2 capsules, 1 x 10 mg and 1 x 1 mg capsules) WATER; Treatment Period 2: 11 mg suspension (5 capsules, 2 x 4 mg and 3 x 1 mg capsules) APPLE JUICE 4. Sequence 6 - Treatment Period 1: 11 mg suspension (2 capsules, 1 x 10 mg and 1 x 1 mg capsules) APPLE JUICE; Treatment Period 2: 11 mg suspension (5 capsules, 2 x 4 mg and 3 x 1 mg capsules) WATER Receives: Drug: Lenvatinib
Lenvatinib 23 mg	Experimental	Arm 3 will have 2 sequences: 1. Sequence 7 - Treatment Period 1: 23 mg suspension (5 capsules, 2 x 10 mg and 3 x 1 mg capsules) taken 23 hours after preparation; Treatment Period 2: 23 mg suspension (5 capsules, 2 x 10 mg and 3 x 1 mg capsules) taken 2 hours after preparation 2. Sequence 8 - Treatment Period 1: 23 mg suspension (5 capsules, 2 x 10 mg and 3 x 1 mg capsules) taken 2 hours after preparation; Treatment Period 2: 23 mg suspension (5 capsules, 2 x 10 mg and 3 x 1 mg capsules) taken 23 hours after preparation Receives: Drug: Lenvatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

Area Under the Plasma Concentration-Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC(0-t))
Blood samples were collected during each Treatment Period at predose and at 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48, 72, 96, and 120 hours postdose. Plasma concentrations of lenvatinib were quantified by a high-performance liquid chromatography/tandem mass spectrometry (LC-MS/MS) method using a previously validated assay. The lower limit of quantitation (LLOQ) was 0.25 ng/mL. Plasma pharmacokinetics (PK) data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of AUC(0-t), which were then summarized as the mean and standard deviation for all participants and expressed as hours·nanogram/milliliter (hr·ng/mL).
Measured: Treatment Period 1: Day 1 (Visit 2), Day 2 (Visit 3), Days 3 to 6 (Visits 4 to 7); Treatment Period 2: Day 8 (Visit 8), Day 9 (Visit 9), Days 10 to 13 (Visits 10 to 13)
Area Under the Plasma Concentration-Time Curve From Zero to Infinity (AUC(0-inf))
Blood samples were collected during each Treatment Period at predose and at 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48, 72, 96, and 120 hours postdose. Plasma concentrations of lenvatinib were quantified by a high-performance LC-MS/MS method using a previously validated assay. The LLOQ was 0.25 ng/mL. Plasma PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates for the AUC(0-inf), which were then summarized as the mean and standard deviation for all participants and expressed as hr·ng/mL.
Measured: Treatment Period 1: Day 1 (Visit 2), Day 2 (Visit 3), Days 3 to 6 (Visits 4 to 7); Treatment Period 2: Day 8 (Visit 8), Day 9 (Visit 9), Days 10 to 13 (Visits 10 to 13)
Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC(0-24))
Blood samples were collected during each Treatment Period at predose up to 24 hours post dose. Plasma concentrations of lenvatinib were quantified by a high-performance LC-MS/MS method using a previously validated assay. The LLOQ was 0.25 ng/mL. Plasma PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates for the AUC(0-24), which were then summarized as the mean and standard deviation for all participants and expressed as hr·ng/mL.
Measured: Treatment Period 1: Predose up to 24 hours post dose
Area Under the Plasma Concentration-Time Curve From Zero to 72 Hours (AUC(0-72))
Blood samples were collected during each Treatment Period at predose up to 72 hours postdose. Plasma concentrations of lenvatinib were quantified by a high-performance LC-MS/MS method using a previously validated assay. The LLOQ was 0.25 ng/mL. Plasma PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates for the AUC(0-72), which were then summarized as the mean and standard deviation for all participants and expressed as hr·ng/mL.
Measured: Treatment Period 1: Predose up to 72 hours postdose
Apparent Clearance (CL/F)
Blood samples were collected during each Treatment Period at predose and at 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48, 72, 96, and 120 hours postdose. Plasma concentrations of lenvatinib were quantified by a high-performance LC-MS/MS method using a previously validated assay. The LLOQ was 0.25 ng/mL. Plasma PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates for the CL/F, which were then summarized as the mean and standard deviation for all participants and expressed as liters/hour.
Measured: Treatment Period 1: Day 1 (Visit 2), Day 2 (Visit 3), Days 3 to 6 (Visits 4 to 7); Treatment Period 2: Day 8 (Visit 8), Day 9 (Visit 9), Days 10 to 13 (Visits 10 to 13)
Apparent Volume of Distribution (Vz/F)
Blood samples were collected during each Treatment Period at predose and at 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48, 72, 96, and 120 hours postdose. Plasma concentrations of lenvatinib were quantified by a high-performance LC-MS/MS method using a previously validated assay. The LLOQ was 0.25 ng/mL. Plasma PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates for the Vz/F, which were then summarized as the mean and standard deviation for all participants and expressed in liters (L).
Measured: Treatment Period 1: Day 1 (Visit 2), Day 2 (Visit 3), Days 3 to 6 (Visits 4 to 7); Treatment Period 2: Day 8 (Visit 8), Day 9 (Visit 9), Days 10 to 13 (Visits 10 to 13)
Maximum Concentration (Cmax) of Lenvatinib in Plasma
Blood samples were collected during each Treatment Period at predose and at 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48, 72, 96, and 120 hours postdose. Plasma concentrations of lenvatinib were quantified by a high-performance LC-MS/MS method using a previously validated assay. The LLOQ was 0.25 ng/mL. Plasma PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of Cmax, which were then summarized as the mean and standard deviation for all participants and expressed as nanograms/milliliter (ng/mL).
Measured: Treatment Period 1: Day 1 (Visit 2), Day 2 (Visit 3), Days 3 to 6 (Visits 4 to 7); Treatment Period 2: Day 8 (Visit 8), Day 9 (Visit 9), Days 10 to 13 (Visits 10 to 13)
Time Prior to the First Measureable Concentration of Lenvatinib (Tlag)
Tlag was defined as the time delay between drug administration and the onset of drug absorption. Blood samples were collected during each Treatment Period at predose and at 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48, 72, 96, and 120 hours postdose. Plasma concentrations of lenvatinib were quantified by a high-performance LC-MS/MS method using a previously validated assay. The LLOQ was 0.25 ng/mL. Plasma PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of tlag, which were then summarized as the median and full range for all participants and expressed in hours.
Measured: Treatment Period 1: Day 1 (Visit 2), Day 2 (Visit 3), Days 3 to 6 (Visits 4 to 7); Treatment Period 2: Day 8 (Visit 8), Day 9 (Visit 9), Days 10 to 13 (Visits 10 to 13)
Time to Maximum Plasma Concentration (Tmax)
Blood samples were collected during each Treatment Period at predose and at 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48, 72, 96, and 120 hours postdose. Plasma concentrations of lenvatinib were quantified by a high-performance LC-MS/MS method using a previously validated assay. The LLOQ was 0.25 ng/mL. Plasma PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of tmax, which were then summarized as the median and full range for all participants and expressed in hours.
Measured: Treatment Period 1: Day 1 (Visit 2), Day 2 (Visit 3), Days 3 to 6 (Visits 4 to 7); Treatment Period 2: Day 8 (Visit 8), Day 9 (Visit 9), Days 10 to 13 (Visits 10 to 13)
Terminal Elimination Phase Half-life (t1/2)
Blood samples were collected during each Treatment Period at predose and at 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48, 72, 96, and 120 hours postdose. Plasma concentrations of lenvatinib were quantified by a high-performance LC-MS/MS method using a previously validated assay. The LLOQ was 0.25 ng/mL. Plasma PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of t1/2, which were then summarized as the median and full range for all participants and expressed in hours.
Measured: Treatment Period 1: Day 1 (Visit 2), Day 2 (Visit 3), Days 3 to 6 (Visits 4 to 7); Treatment Period 2: Day 8 (Visit 8), Day 9 (Visit 9), Days 10 to 13 (Visits 10 to 13)
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Lenvatinib
Safety assessment consisted on monitoring and recording all treatment-emergent adverse events (TEAEs) and SAEs; as well as laboratory evaluations for hematology, blood chemistry, and urine values; periodic measurement of vital signs, electrocardiograms (ECGs); and physical examinations. A TEAE was defined as an adverse events that: 1) emerged during treatment and up to 7 days from the last treatment, having been absent before treatment or at baseline, 2) reemerged during treatment, having been present at Baseline but stopped before treatment, or 3) worsened in severity during treatment relative to the state before treatment, when continuous.
Measured: From date of first dose of study treatment to date of last dose of study treatment, up to approximately 2 months 10 days

Secondary outcomes (1)

Summary Scores for Palatability of Lenvatinib
A hedonic Visual Analog Scale (VAS) was used to assess taste likability or "palatability" between a) lenvatinib suspension formulated with water versus the capsule formulation, b) a lenvatinib suspension formulated with with apple juice versus one formulated with water, and c) a lenvatinib suspension formulated with water administered 23 hours versus 2 hours after preparation. All participants selected one face based on flavor, smell, sweetness, acidity, saltiness, bitterness, and texture or mouth feel for each formulation they consumed. Each face had an associated score (1: Very Bad (angry face), 2: Bad (sad face), 3: Maybe Good or Maybe Bad (neutral face), 4: Good (smiling face), 5: Very Good (laughing face)). The VAS hedonic scale scores were summarized using descriptive statistics separately for each arm by formulation (Arm 1), number of capsules (2 vs 5 capsules) and preparation type (water vs apple juice) (Arm 2), and time of administration relative to preparation (Arm 3).
Measured: Treatment Period 1, Day 1 (Visit 2); Treatment Period 2, Day 8 (Visit 8)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 2014Aug 2014

First posted8 Jun 2016 (estimated)
Study startAug 2014
Primary completionAug 2014
Study completionAug 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
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: 60 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02792829
Sponsor's protocol ID: E7080-A001-009
Status last verified: Mar 2018
First submitted: 15 Oct 2015
Last updated: 14 Mar 2019
Results posted: Yes, on ClinicalTrials.gov

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 14 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized Three-Arm, Single-dose, Two-period Crossover Study to Evaluate the Relative Bioavailability and Palatability of a Lenvatinib Suspension Compared to the Capsule Formulation in Adult Healthy Volunteers
ClinicalTrials.gov ID: NCT02792829
Acronym / sponsor ID: E7080-A001-009
Conditions: Healthy Volunteers
Keywords: Bioavailability of Lenvatinib suspension, Palatability of Lenvatinib suspension, Lenvatinib, Lenvima, E7080, Capsule formulation, Healthy volunteers
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 60 participants (actual)
Lead sponsor: Eisai Inc.Industry (pharma, biotech, devices)
Study start: Aug 2014
Primary completion: Aug 2014 (actual)
Study completion: Aug 2014 (actual)
First posted: 8 Jun 2016 (estimated)
Results: Posted 14 Mar 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Lenvatinib 11 mg (suspension formulation)	Experimental	Drug: LenvatinibArm 1 will have 2 sequences: 1. Sequence 1 - Treatment Period 1: 11 mg suspension (2 capsules, 1 x 10 mg and 1 x 1 mg); Treatment Period 2: 11 mg capsules (2 capsules, 1 x 10 mg and 1 x 1 mg) 2. Sequence 2 - Treatment Period 1: 11 mg capsules (2 capsules, 1 x 10 mg and 1 x 1 mg); Treatment Period 2: 11 mg suspension (2 capsules, 1 x 10 mg and 1 x 1 mg)
Lenvatinib 11 mg (2 vs 5 capsules)	Experimental	Drug: LenvatinibArm 2 will have 4 sequences: 1. Sequence 3 - Treatment Period 1: 11 mg suspension (5 capsules, 2 x 4 mg and 3 x 1 mg) WATER; Treatment Period 2: 11 mg suspension (2 capsules, 1 x 10 mg and 1 x 1 mg) APPLE JUICE 2. Sequence 4 - Treatment Period 1: 11 mg suspension (5 capsules, 2 x 4 mg and 3 x 1 mg capsules) APPLE JUICE; Treatment Period 2: 11 mg suspension (2 capsules, 1 x 10 mg and 1 x 1 mg capsules) WATER 3. Sequence 5 - Treatment Period 1: 11 mg suspension (2 capsules, 1 x 10 mg and 1 x 1 mg capsules) WATER; Treatment Period 2: 11 mg suspension (5 capsules, 2 x 4 mg and 3 x 1 mg capsules) APPLE JUICE 4. Sequence 6 - Treatment Period 1: 11 mg suspension (2 capsules, 1 x 10 mg and 1 x 1 mg capsules) APPLE JUICE; Treatment Period 2: 11 mg suspension (5 capsules, 2 x 4 mg and 3 x 1 mg capsules) WATER
Lenvatinib 23 mg	Experimental	Drug: LenvatinibArm 3 will have 2 sequences: 1. Sequence 7 - Treatment Period 1: 23 mg suspension (5 capsules, 2 x 10 mg and 3 x 1 mg capsules) taken 23 hours after preparation; Treatment Period 2: 23 mg suspension (5 capsules, 2 x 10 mg and 3 x 1 mg capsules) taken 2 hours after preparation 2. Sequence 8 - Treatment Period 1: 23 mg suspension (5 capsules, 2 x 10 mg and 3 x 1 mg capsules) taken 2 hours after preparation; Treatment Period 2: 23 mg suspension (5 capsules, 2 x 10 mg and 3 x 1 mg capsules) taken 23 hours after preparation

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (11 listed)

Healthy male and female participants age greater than or equal to 18 years and less than or equal to 55 years old at time of informed consent
Nonsmokers or smokers who smoke no more than 10 cigarettes per day
BMI greater than or equal to 18 and less than or equal to 32 kg/m2 at screening
Adequate liver function, defined as: bilirubin less than or equal to 1.5 X the upper limit of normal (ULN), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and alanine aminotransferase (ALT) less than or equal to 1.5 X ULN
Adequate renal function defined as creatinine clearance greater than 70 mL/min calculated using the Cockcroft and Gault formula

Key exclusion criteria (17 listed)

Clinically significant illness that requires medical treatment within 8 weeks prior, or a clinically significant infection that requires medical treatment within 4 weeks prior to dosing
Evidence of disease that may influence the outcome of the study, within 4 weeks prior to dosing; eg, psychiatric disorders and disorders of the gastrointestinal (GI) tract, liver, kidney, respiratory system, endocrine system, hematological system, neurological system, or cardiovascular system, or participants who have a congenital abnormality in metabolism
Any history of surgery that may affect PK profiles of lenvatinib eg, hepatectomy, nephrotomy, digestive organ resection, at screening or baseline
Any clinically abnormal symptom or organ impairment found by medical history, physical examinations, vital signs, electrocardiogram (ECG) finding, or laboratory test results that requires medical treatment at screening or baseline
Prolonged QTcF interval (QTcF greater than 450 ms) demonstrated on ECG at screening or baseline

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: Lenvima; E7080All participants will receive one single dose in each of the 2 treatment periods (total of 2 doses). The total duration of the treatment periods is 12 days (6 days per period) in healthy adult volunteers.	Drug	Lenvatinib 11 mg (2 vs 5 capsules), Lenvatinib 11 mg (suspension formulation), Lenvatinib 23 mg

Primary outcome

Area Under the Plasma Concentration-Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC(0-t))
Time frame: Treatment Period 1: Day 1 (Visit 2), Day 2 (Visit 3), Days 3 to 6 (Visits 4 to 7); Treatment Period 2: Day 8 (Visit 8), Day 9 (Visit 9), Days 10 to 13 (Visits 10 to 13)
Blood samples were collected during each Treatment Period at predose and at 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48, 72, 96, and 120 hours postdose. Plasma concentrations of lenvatinib were quantified by a high-performance liquid chromatography/tandem mass spectrometry (LC-MS/MS) method using a previously validated assay. The lower limit of quantitation (LLOQ) was 0.25 ng/mL. Plasma pharmacokinetics (PK) data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of AUC(0-t), which were then summarized as the mean and standard deviation for all participants and expressed as hours·nanogram/milliliter (hr·ng/mL).
Area Under the Plasma Concentration-Time Curve From Zero to Infinity (AUC(0-inf))
Time frame: Treatment Period 1: Day 1 (Visit 2), Day 2 (Visit 3), Days 3 to 6 (Visits 4 to 7); Treatment Period 2: Day 8 (Visit 8), Day 9 (Visit 9), Days 10 to 13 (Visits 10 to 13)
Blood samples were collected during each Treatment Period at predose and at 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48, 72, 96, and 120 hours postdose. Plasma concentrations of lenvatinib were quantified by a high-performance LC-MS/MS method using a previously validated assay. The LLOQ was 0.25 ng/mL. Plasma PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates for the AUC(0-inf), which were then summarized as the mean and standard deviation for all participants and expressed as hr·ng/mL.
Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC(0-24))
Time frame: Treatment Period 1: Predose up to 24 hours post dose
Blood samples were collected during each Treatment Period at predose up to 24 hours post dose. Plasma concentrations of lenvatinib were quantified by a high-performance LC-MS/MS method using a previously validated assay. The LLOQ was 0.25 ng/mL. Plasma PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates for the AUC(0-24), which were then summarized as the mean and standard deviation for all participants and expressed as hr·ng/mL.
Area Under the Plasma Concentration-Time Curve From Zero to 72 Hours (AUC(0-72))
Time frame: Treatment Period 1: Predose up to 72 hours postdose
Blood samples were collected during each Treatment Period at predose up to 72 hours postdose. Plasma concentrations of lenvatinib were quantified by a high-performance LC-MS/MS method using a previously validated assay. The LLOQ was 0.25 ng/mL. Plasma PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates for the AUC(0-72), which were then summarized as the mean and standard deviation for all participants and expressed as hr·ng/mL.
Apparent Clearance (CL/F)
Time frame: Treatment Period 1: Day 1 (Visit 2), Day 2 (Visit 3), Days 3 to 6 (Visits 4 to 7); Treatment Period 2: Day 8 (Visit 8), Day 9 (Visit 9), Days 10 to 13 (Visits 10 to 13)
Blood samples were collected during each Treatment Period at predose and at 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48, 72, 96, and 120 hours postdose. Plasma concentrations of lenvatinib were quantified by a high-performance LC-MS/MS method using a previously validated assay. The LLOQ was 0.25 ng/mL. Plasma PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates for the CL/F, which were then summarized as the mean and standard deviation for all participants and expressed as liters/hour.
Apparent Volume of Distribution (Vz/F)
Time frame: Treatment Period 1: Day 1 (Visit 2), Day 2 (Visit 3), Days 3 to 6 (Visits 4 to 7); Treatment Period 2: Day 8 (Visit 8), Day 9 (Visit 9), Days 10 to 13 (Visits 10 to 13)
Blood samples were collected during each Treatment Period at predose and at 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48, 72, 96, and 120 hours postdose. Plasma concentrations of lenvatinib were quantified by a high-performance LC-MS/MS method using a previously validated assay. The LLOQ was 0.25 ng/mL. Plasma PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates for the Vz/F, which were then summarized as the mean and standard deviation for all participants and expressed in liters (L).
Maximum Concentration (Cmax) of Lenvatinib in Plasma
Time frame: Treatment Period 1: Day 1 (Visit 2), Day 2 (Visit 3), Days 3 to 6 (Visits 4 to 7); Treatment Period 2: Day 8 (Visit 8), Day 9 (Visit 9), Days 10 to 13 (Visits 10 to 13)
Blood samples were collected during each Treatment Period at predose and at 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48, 72, 96, and 120 hours postdose. Plasma concentrations of lenvatinib were quantified by a high-performance LC-MS/MS method using a previously validated assay. The LLOQ was 0.25 ng/mL. Plasma PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of Cmax, which were then summarized as the mean and standard deviation for all participants and expressed as nanograms/milliliter (ng/mL).
Time Prior to the First Measureable Concentration of Lenvatinib (Tlag)
Time frame: Treatment Period 1: Day 1 (Visit 2), Day 2 (Visit 3), Days 3 to 6 (Visits 4 to 7); Treatment Period 2: Day 8 (Visit 8), Day 9 (Visit 9), Days 10 to 13 (Visits 10 to 13)
Tlag was defined as the time delay between drug administration and the onset of drug absorption. Blood samples were collected during each Treatment Period at predose and at 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48, 72, 96, and 120 hours postdose. Plasma concentrations of lenvatinib were quantified by a high-performance LC-MS/MS method using a previously validated assay. The LLOQ was 0.25 ng/mL. Plasma PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of tlag, which were then summarized as the median and full range for all participants and expressed in hours.
Time to Maximum Plasma Concentration (Tmax)
Time frame: Treatment Period 1: Day 1 (Visit 2), Day 2 (Visit 3), Days 3 to 6 (Visits 4 to 7); Treatment Period 2: Day 8 (Visit 8), Day 9 (Visit 9), Days 10 to 13 (Visits 10 to 13)
Blood samples were collected during each Treatment Period at predose and at 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48, 72, 96, and 120 hours postdose. Plasma concentrations of lenvatinib were quantified by a high-performance LC-MS/MS method using a previously validated assay. The LLOQ was 0.25 ng/mL. Plasma PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of tmax, which were then summarized as the median and full range for all participants and expressed in hours.
Terminal Elimination Phase Half-life (t1/2)
Time frame: Treatment Period 1: Day 1 (Visit 2), Day 2 (Visit 3), Days 3 to 6 (Visits 4 to 7); Treatment Period 2: Day 8 (Visit 8), Day 9 (Visit 9), Days 10 to 13 (Visits 10 to 13)
Blood samples were collected during each Treatment Period at predose and at 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48, 72, 96, and 120 hours postdose. Plasma concentrations of lenvatinib were quantified by a high-performance LC-MS/MS method using a previously validated assay. The LLOQ was 0.25 ng/mL. Plasma PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of t1/2, which were then summarized as the median and full range for all participants and expressed in hours.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Lenvatinib
Time frame: From date of first dose of study treatment to date of last dose of study treatment, up to approximately 2 months 10 days
Safety assessment consisted on monitoring and recording all treatment-emergent adverse events (TEAEs) and SAEs; as well as laboratory evaluations for hematology, blood chemistry, and urine values; periodic measurement of vital signs, electrocardiograms (ECGs); and physical examinations. A TEAE was defined as an adverse events that: 1) emerged during treatment and up to 7 days from the last treatment, having been absent before treatment or at baseline, 2) reemerged during treatment, having been present at Baseline but stopped before treatment, or 3) worsened in severity during treatment relative to the state before treatment, when continuous.

1 secondary outcome

Summary Scores for Palatability of Lenvatinib
Time frame: Treatment Period 1, Day 1 (Visit 2); Treatment Period 2, Day 8 (Visit 8)

Results and safety

Results posted to the registry on 14 Mar 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Arm 1: Lenvatinib 11 mg: Suspension+ Capsules (CAP)	10	10
Arm 1: Lenvatinib 11 mg: CAP+ Suspension	10	10
Arm 2:Lenvatinib 11mg Suspension:5 CAP-Water+2 Cap-Apple Juice	5	5
Arm 2:Lenvatinib 11mg Suspension:5 CAP-Apple Juice+2 CAP-Water	5	5
Arm 2:Lenvatinib 11mg Suspension:2 CAP-Water+5 CAP-Apple Juice	5	5
Arm 2:Lenvatinib 11mg Suspension:2 CAP-Apple Juice+5 CAP-Water	5	5
Arm 3:Lenvatinib 23mg Suspension Taken at:23 Hours+2 Hours	10	10
Arm 3:Lenvatinib 23mg Suspension Taken at:2 Hours+23 Hours	10	10

Primary outcome: Area Under the Plasma Concentration-Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC(0-t))

Time frame: Treatment Period 1: Day 1 (Visit 2), Day 2 (Visit 3), Days 3 to 6 (Visits 4 to 7); Treatment Period 2: Day 8 (Visit 8), Day 9 (Visit 9), Days 10 to 13 (Visits 10 to 13). Mean (Standard Deviation). Unit: hr·ng/mL

Measure	Arm 1: 11 mg Lenvatinib Suspension in Water n = 19	Arm 1: 11 mg Lenvatinib Capsule With Water n = 20	Arm 2: 11 mg Lenvatinib (Suspension of 5 Capsules in Water) n = 10	Arm 2: 11 mg Lenvatinib (Suspension of 5 Capsules in Juice) n = 9	Arm 2: 11 mg Lenvatinib (Suspension of 2 Capsules in Water) n = 10	Arm 2: 11 mg Lenvatinib (Suspension of 2 Capsules in Juice) n = 10	Arm 3: 23 mg Lenvatinib Suspension in Water (23 Hours) n = 18	Arm 3: 23 mg Lenvatinib Suspension in Water (2 Hours) n = 19
Value	1330 (452)	1340 (482)	1020 (172)	1500 (706)	1340 (519)	1010 (160)	3010 (919)	3210 (1040)

Population analysed: The PK Analysis Set was the group of subjects who had sufficient PK data for at least 1 PK parameter to be derived. Subjects with predose lenvatinib concentration \>5% of their own Cmax, and subjects who experienced emesis at or before 2x median tmax were excluded from data analysis for bioavailability.

Primary outcome: Area Under the Plasma Concentration-Time Curve From Zero to Infinity (AUC(0-inf))

Measure	Arm 1: 11 mg Lenvatinib Suspension in Water n = 19	Arm 1: 11 mg Lenvatinib Capsule With Water n = 20	Arm 2: Lenvatinib 11 mg (Suspension of 5 Capsules in Water) n = 10	Arm 2: Lenvatinib 11 mg (Suspension of 5 Capsules in Juice) n = 9	Arm 2: Lenvatinib 11 mg (Suspension of 2 Capsules in Water) n = 10	Arm 2: Lenvatinib 11 mg (Suspension of 2 Capsules in Juice) n = 10	Arm 3: 23 mg Lenvatinib Suspension in Water (23 Hours) n = 17	Arm 3: 23 mg Lenvatinib Suspension in Water (2 Hours) n = 19
Value	1360 (456)	1360 (490)	1040 (177)	1530 (720)	1370 (532)	1030 (161)	2970 (910)	3240 (1050)

Population analysed: PK analysis set

Primary outcome: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC(0-24))

Time frame: Treatment Period 1: Predose up to 24 hours post dose. Mean (Standard Deviation). Unit: h·ng/mL

Measure	Arm 1: 11 mg Lenvatinib Suspension in Water n = 19	Arm 1: 11 mg Lenvatinib Capsule With Water n = 20	Arm 2: Lenvatinib 11 mg (Suspension of 5 Capsules in Water) n = 10	Arm 2: Lenvatinib 11 mg (Suspension of 5 Capsules in Juice) n = 8	Arm 2: Lenvatinib 11 mg (Suspension of 2 Capsules in Water) n = 10	Arm 2: Lenvatinib 11 mg (Suspension of 2 Capsules in Juice) n = 10	Arm 3: 23 mg Lenvatinib Suspension in Water (23 Hours) n = 18	Arm 3: 23 mg Lenvatinib Suspension in Water (2 Hours) n = 19
Value	1060 (377)	1050 (383)	815 (136)	1150 (564)	1070 (415)	804 (136)	2540 (785)	2720 (858)

Population analysed: PK analysis set

Primary outcome: Area Under the Plasma Concentration-Time Curve From Zero to 72 Hours (AUC(0-72))

Time frame: Treatment Period 1: Predose up to 72 hours postdose. Mean (Standard Deviation). Unit: hr·ng/mL

Measure	Arm 1: 11 mg Lenvatinib Suspension in Water n = 19	Arm 1: 11 mg Lenvatinib Capsule With Water n = 20	Arm 2: Lenvatinib 11 mg (Suspension of 5 Capsules in Water) n = 10	Arm 2: Lenvatinib 11 mg (Suspension of 5 Capsules in Juice) n = 9	Arm 2: Lenvatinib 11 mg (Suspension of 2 Capsules in Water) n = 10	Arm 2: Lenvatinib 11 mg (Suspension of 2 Capsules in Juice) n = 10	Arm 3: 23 mg Lenvatinib Suspension in Water (23 Hours) n = 18	Arm 3: 23 mg Lenvatinib Suspension in Water (2 Hours) n = 19
Value	1280 (437)	1290 (466)	987 (164)	1430 (668)	1290 (500)	971 (152)	2930 (887)	3130 (1010)

Population analysed: PK analysis set

1 secondary outcome is reported in the full results.

Adverse events

Time frame: From date of first dose of study treatment to date of last dose of study treatment, up to approximately 2 months 10 days. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Arm 1: 11 mg Lenvatinib Suspension in Water	0 of 19 (0%)	4 of 19 (21.1%)	0 of 19
Arm 1: 11 mg Lenvatinib Capsule With Water	0 of 20 (0%)	6 of 20 (30%)	0 of 20
Arm 2: 11 mg Lenvatinib (Suspension of 5 Capsules in Water)	0 of 10 (0%)	1 of 10 (10%)	0 of 10
Arm 2: 11 mg Lenvatinib (Suspension of 5 Capsules in Juice)	0 of 9 (0%)	2 of 9 (22.2%)	0 of 9
Arm 2: 11 mg Lenvatinib (Suspension of 2 Capsules in Water)	0 of 10 (0%)	4 of 10 (40%)	0 of 10
Arm 2: 11 mg Lenvatinib (Suspension of 2 Capsules in Juice)	0 of 10 (0%)	4 of 10 (40%)	0 of 10
Arm 3: 23 mg Lenvatinib Suspension in Water (23 Hours)	0 of 18 (0%)	3 of 18 (16.7%)	0 of 18
Arm 3: 23 mg Lenvatinib Suspension in Water (2 Hours)	0 of 19 (0%)	4 of 19 (21.1%)	0 of 19

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Mar 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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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.

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 testing Lenvatinib in people with 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 11 inclusion and 17 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 14 Mar 2019. 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?

Yes. Results are posted in the registry (first posted 14 Mar 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Area Under the Plasma Concentration-Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC(0-t)) (time frame: Treatment Period 1: Day 1 (Visit 2), Day 2 (Visit 3), Days 3 to 6 (Visits 4 to 7); Treatment Period 2: Day 8 (Visit 8), Day 9 (Visit 9), Days 10 to 13 (Visits 10 to 13)). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02792829.

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 14 Mar 2019.