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

• Sponsor: Eisai Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02792829
• Collaborator: (none)
• Enrollment: 60
• Location: 1
• Arms: 3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: Lenvatinib	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Study Start Date: Aug 1, 2014
• Actual Primary Completion Date: Aug 1, 2014
• Actual Study Completion Date: Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lenvatinib 11 mg (suspension formulation) Arm 1 will have 2 sequences: 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) 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)	Drug: Lenvatinib; 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.; Other Names: Lenvima; E7080
Experimental: Lenvatinib 11 mg (2 vs 5 capsules) Arm 2 will have 4 sequences: 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 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 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 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	Drug: Lenvatinib; 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.; Other Names: Lenvima; E7080
Experimental: Lenvatinib 23 mg Arm 3 will have 2 sequences: 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 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	Drug: Lenvatinib; 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.; Other Names: Lenvima; E7080

Outcome Measures

Primary Outcome Measures

1. Area Under the Plasma Concentration-Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC(0-t)) [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).

2. Area Under the Plasma Concentration-Time Curve From Zero to Infinity (AUC(0-inf)) [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.

3. Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC(0-24)) [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.

4. Area Under the Plasma Concentration-Time Curve From Zero to 72 Hours (AUC(0-72)) [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.

5. Apparent Clearance (CL/F) [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.

6. Apparent Volume of Distribution (Vz/F) [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).

7. Maximum Concentration (Cmax) of Lenvatinib in Plasma [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).

8. Time Prior to the First Measureable Concentration of Lenvatinib (Tlag) [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.

9. Time to Maximum Plasma Concentration (Tmax) [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.

10. Terminal Elimination Phase Half-life (t1/2) [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.

11. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Lenvatinib [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.

Secondary Outcome Measures

1. Summary Scores for Palatability of Lenvatinib [Treatment Period 1, Day 1 (Visit 2); Treatment Period 2, Day 8 (Visit 8)]

   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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. 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

2. Nonsmokers or smokers who smoke no more than 10 cigarettes per day

3. BMI greater than or equal to 18 and less than or equal to 32 kg/m2 at screening

4. 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

5. Adequate renal function defined as creatinine clearance greater than 70 mL/min calculated using the Cockcroft and Gault formula

6. 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.

7. 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)

8. 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.

9. 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.

10. Provide written informed consent

11. Willing and able to comply with all aspects of the protocol

Exclusion Criteria:

1. 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

2. 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

3. Any history of surgery that may affect PK profiles of lenvatinib eg, hepatectomy, nephrotomy, digestive organ resection, at screening or baseline

4. 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

5. Prolonged QTcF interval (QTcF greater than 450 ms) demonstrated on ECG at screening or baseline

6. Known history of clinically significant drug allergy at Screening or Baseline

7. Known history of food allergies or presently experiencing significant seasonal or perennial allergy at Screening or Baseline

8. Known history of sensitivity to any of the components of the test products

9. Known to be human immunodeficiency virus (HIV) positive at screening

10. Active viral hepatitis (A, B, or C) as demonstrated by positive serology at screening

11. 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

12. Engagement in strenuous exercise within 2 weeks prior to check-in (eg, marathon runners, weight lifters)

13. 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

14. Intake of herbal preparations containing St. John's Wort within 4 weeks prior to dosing

15. Use of prescription drugs within 4 weeks prior to dosing

16. Intake of over-the-counter (OTC) medications within 2 weeks prior to dosing

17. Receipt of blood products within 4 weeks, or donation of blood within 8 weeks, or donation of plasma within 1 week prior to dosing

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Las Vegas	Nevada	United States

Sponsors and Collaborators

• Eisai Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eisai Inc.
• ClinicalTrials.gov Identifier: NCT02792829
• Other Study ID Numbers: E7080-A001-009
• First Posted: Jun 8, 2016
• Last Update Posted: Mar 14, 2019
• Last Verified: Mar 1, 2018

• Keywords provided by Eisai Inc.: Bioavailability of Lenvatinib suspension; Palatability of Lenvatinib suspension; Lenvatinib; Lenvima; E7080; Capsule formulation; Healthy volunteers
• Additional relevant MeSH terms: Lenvatinib

Study Results

Participant Flow

Arm/Group Title	Arm 1: Lenvatinib 11 mg: Suspension+ Capsules (CAP)	Arm 1: Lenvatinib 11 mg: CAP+ Suspension	Arm 2:Lenvatinib 11mg Suspension:5 CAP-Water+2 Cap-Apple Juice	Arm 2:Lenvatinib 11mg Suspension:5 CAP-Apple Juice+2 CAP-Water	Arm 2:Lenvatinib 11mg Suspension:2 CAP-Water+5 CAP-Apple Juice	Arm 2:Lenvatinib 11mg Suspension:2 CAP-Apple Juice+5 CAP-Water	Arm 3:Lenvatinib 23mg Suspension Taken at:23 Hours+2 Hours	Arm 3:Lenvatinib 23mg Suspension Taken at:2 Hours+23 Hours
Arm/Group Description	Participants received lenvatinib 11 mg (milligram), suspension in water (prepared using 1 capsule of 10 mg and 1 capsule of 1 mg) on Day 1 of Treatment Period 1 followed by a 6-days wash-out period, further followed by lenvatinib 11 mg, capsules (1 capsules of 10mg and 1 capsules of 1 mg) on Day 8 of Treatment Period 2. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	Participants received lenvatinib 11 mg, capsules (1 capsules of 10mg and 1 capsules of 1 mg) on Day 1 of Treatment Period 1 followed by a 6-days wash-out period, further followed by lenvatinib 11 mg, suspension in water (prepared using 1 capsule of 10 mg and 1 capsule of 1 mg) on Day 8 of Treatment Period 2. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	Participants received lenvatinib 11mg, suspension in water (prepared using 2 capsule of 4 mg each and 3 capsule of 1 mg each) on Day 1 of Treatment Period 1 followed by a 6-days wash-out period, further followed by lenvatinib 11mg, suspension in apple juice (prepared using 1 capsules of 10mg and 1 capsules of 1 mg) on Day 8 of Treatment Period 2. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	Participants received lenvatinib 11mg, suspension in apple juice (prepared using 2 capsule of 4 mg each and 3 capsule of 1 mg each) on Day 1 of Treatment Period 1 followed by a 6-days wash-out period, further followed by lenvatinib 11mg, suspension in water (prepared using 1 capsule of 10 mg and 1 capsule of 1 mg) on Day 8 of Treatment Period 2. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	Participants received lenvatinib 11mg, suspension in water (prepared using 1 capsule of 10 mg and 1 capsule of 1 mg) on Day 1 of Treatment Period 1 followed by a 6-days wash-out period, further followed by lenvatinib 11mg, suspension in apple juice (prepared using 2 capsules of 4 mg each and 3 capsules of 1 mg each) on Day 8 of Treatment Period 2. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	Participants received lenvatinib 11mg, suspension in apple juice (prepared using 1 capsule of 10 mg and 1 capsule of 1 mg) on Day 1 of Treatment Period 1 followed by a 6-days wash-out period, further followed by lenvatinib 11mg, suspension in water (prepared using 2 capsules of 4 mg each and 3 capsules of 1 mg) on Day 8 on Treatment Period 2. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	Participants received lenvatinib 11mg, suspension in water taken 23 hours after preparation (prepared using 2 capsules of 10 mg each and 3 capsules of 1 mg of each) on Day 1 of Treatment Period 1 followed by a 6-days wash-out period, further followed by lenvatinib 23mg, suspension in water taken 2 hours after preparation (prepared using 2 capsules of 10 mg each and 3 capsules of 1 mg) on Day 8 of Treatment Period 2. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	Participants received lenvatinib 23mg, suspension in water taken 2 hours after preparation (prepared using 2 capsules of 10 mg each and 3 capsules of 1 mg of each) on Day 1 of Treatment Period 1 followed by a 6-days wash-out period, further followed by lenvatinib 23mg, suspension in water taken 23 hours after preparation (prepared using 2 capsules of 10 mg each and 3 capsules of 1 mg) on Day 8 of Treatment Period 2. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.
Period Title: Treatment Period 1
STARTED	10	10	5	5	5	5	10	10
COMPLETED	10	10	5	5	5	5	10	10
NOT COMPLETED	0	0	0	0	0	0	0	0
Period Title: Treatment Period 1
STARTED	10	10	5	5	5	5	10	10
COMPLETED	10	10	5	5	5	5	10	10
NOT COMPLETED	0	0	0	0	0	0	0	0
Period Title: Treatment Period 1
STARTED	10	10	5	5	5	5	10	10
COMPLETED	10	9	5	5	4	5	9	8
NOT COMPLETED	0	1	0	0	1	0	1	2

Baseline Characteristics

Arm/Group Title	Arm 1: 11 mg Lenvatinib Suspension in Water	Arm 1: 11 mg Lenvatinib Capsule With Water	Arm 2: 11 mg Lenvatinib (Suspension of 5 Capsules in Water)	Arm 2: 11 mg Lenvatinib (Suspension of 5 Capsules in Juice)	Arm 2: 11 mg Lenvatinib (Suspension of 2 Capsules in Water)	Arm 2: 11 mg Lenvatinib (Suspension of 2 Capsules in Juice)	Arm 3: 23 mg Lenvatinib Suspension in Water (23 Hours)	Arm 3: 23 mg Lenvatinib Suspension in Water (2 Hours)	Total
Arm/Group Description	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (11 mg) suspension in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the administered lenvatinib (11 mg) capsules with 240 mL (8 fluid ounces) of water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 5 capsules of lenvatinib (11 mg total) in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 5 capsules of lenvatinib (11 mg total) in apple juice. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 2 capsules of lenvatinib (11 mg total) in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 2 capsules of lenvatinib (11 mg total) in apple juice. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (23 mg) suspension in water, which had been prepared 23 hours prior to administration. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (23 mg) suspension in water, which had been prepared 2 hours prior to administration. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	Total of all reporting groups
Overall Participants	10	10	5	5	5	5	10	10	60
Age, Customized (Count of Participants)
18 to 65 years	10 100%	10 100%	5 100%	5 100%	5 100%	5 100%	10 100%	10 100%	60 100%
Sex/Gender, Customized (Number) [Number]
Male	9 90%	7 70%	5 100%	3 60%	3 60%	3 60%	5 50%	7 70%	42 70%
Female	1 10%	3 30%	0 0%	2 40%	2 40%	2 40%	5 50%	3 30%	18 30%

Outcome Measures

1. Primary Outcome

Title	Area Under the Plasma Concentration-Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC(0-t))
Description	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).
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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Arm 1: 11 mg Lenvatinib Suspension in Water	Arm 1: 11 mg Lenvatinib Capsule With Water	Arm 2: 11 mg Lenvatinib (Suspension of 5 Capsules in Water)	Arm 2: 11 mg Lenvatinib (Suspension of 5 Capsules in Juice)	Arm 2: 11 mg Lenvatinib (Suspension of 2 Capsules in Water)	Arm 2: 11 mg Lenvatinib (Suspension of 2 Capsules in Juice)	Arm 3: 23 mg Lenvatinib Suspension in Water (23 Hours)	Arm 3: 23 mg Lenvatinib Suspension in Water (2 Hours)
Arm/Group Description	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (11 mg) suspension in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the administered lenvatinib (11 mg) capsules with 240 mL (8 fluid ounces) of water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 5 capsules of lenvatinib (11 mg total) in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 5 capsules of lenvatinib (11 mg total) in apple juice. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 2 capsules of lenvatinib (11 mg total) in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 2 capsules of lenvatinib (11 mg total) in apple juice. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (23 mg) suspension in water, which had been prepared 23 hours prior to administration. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (23 mg) suspension in water, which had been prepared 2 hours prior to administration. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.
Measure Participants	19	20	10	9	10	10	18	19
Mean (Standard Deviation) [hr·ng/mL]	1330 (452)	1340 (482)	1020 (172)	1500 (706)	1340 (519)	1010 (160)	3010 (919)	3210 (1040)

2. Primary Outcome

Title	Area Under the Plasma Concentration-Time Curve From Zero to Infinity (AUC(0-inf))
Description	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.
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)

Outcome Measure Data

Analysis Population Description

PK analysis set

Arm/Group Title	Arm 1: 11 mg Lenvatinib Suspension in Water	Arm 1: 11 mg Lenvatinib Capsule With Water	Arm 2: Lenvatinib 11 mg (Suspension of 5 Capsules in Water)	Arm 2: Lenvatinib 11 mg (Suspension of 5 Capsules in Juice)	Arm 2: Lenvatinib 11 mg (Suspension of 2 Capsules in Water)	Arm 2: Lenvatinib 11 mg (Suspension of 2 Capsules in Juice)	Arm 3: 23 mg Lenvatinib Suspension in Water (23 Hours)	Arm 3: 23 mg Lenvatinib Suspension in Water (2 Hours)
Arm/Group Description	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (11 mg) suspension in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the administered lenvatinib (11 mg) capsules with 240 mL (8 fluid ounces) of water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 5 capsules of lenvatinib (11 mg total) in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 5 capsules of lenvatinib (11 mg total) in apple juice. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 2 capsules of lenvatinib (11 mg total) in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 2 capsules of lenvatinib (11 mg total) in apple juice. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (23 mg) suspension in water, which had been prepared 23 hours prior to administration. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (23 mg) suspension in water, which had been prepared 23 hours prior to administration. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.
Measure Participants	19	20	10	9	10	10	17	19
Mean (Standard Deviation) [hr·ng/mL]	1360 (456)	1360 (490)	1040 (177)	1530 (720)	1370 (532)	1030 (161)	2970 (910)	3240 (1050)

3. Primary Outcome

Title	Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC(0-24))
Description	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.
Time Frame	Treatment Period 1: Predose up to 24 hours post dose

Outcome Measure Data

Analysis Population Description

PK analysis set

Arm/Group Title	Arm 1: 11 mg Lenvatinib Suspension in Water	Arm 1: 11 mg Lenvatinib Capsule With Water	Arm 2: Lenvatinib 11 mg (Suspension of 5 Capsules in Water)	Arm 2: Lenvatinib 11 mg (Suspension of 5 Capsules in Juice)	Arm 2: Lenvatinib 11 mg (Suspension of 2 Capsules in Water)	Arm 2: Lenvatinib 11 mg (Suspension of 2 Capsules in Juice)	Arm 3: 23 mg Lenvatinib Suspension in Water (23 Hours)	Arm 3: 23 mg Lenvatinib Suspension in Water (2 Hours)
Arm/Group Description	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (11 mg) suspension in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the administered lenvatinib (11 mg) capsules with 240 mL (8 fluid ounces) of water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 5 capsules of lenvatinib (11 mg total) in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 5 capsules of lenvatinib (11 mg total) in apple juice. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 2 capsules of lenvatinib (11 mg total) in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 2 capsules of lenvatinib (11 mg total) in apple juice. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (23 mg) suspension in water, which had been prepared 23 hours prior to administration. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (23 mg) suspension in water, which had been prepared 23 hours prior to administration. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.
Measure Participants	19	20	10	8	10	10	18	19
Mean (Standard Deviation) [h·ng/mL]	1060 (377)	1050 (383)	815 (136)	1150 (564)	1070 (415)	804 (136)	2540 (785)	2720 (858)

4. Primary Outcome

Title	Area Under the Plasma Concentration-Time Curve From Zero to 72 Hours (AUC(0-72))
Description	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.
Time Frame	Treatment Period 1: Predose up to 72 hours postdose

Outcome Measure Data

Analysis Population Description

PK analysis set

Arm/Group Title	Arm 1: 11 mg Lenvatinib Suspension in Water	Arm 1: 11 mg Lenvatinib Capsule With Water	Arm 2: Lenvatinib 11 mg (Suspension of 5 Capsules in Water)	Arm 2: Lenvatinib 11 mg (Suspension of 5 Capsules in Juice)	Arm 2: Lenvatinib 11 mg (Suspension of 2 Capsules in Water)	Arm 2: Lenvatinib 11 mg (Suspension of 2 Capsules in Juice)	Arm 3: 23 mg Lenvatinib Suspension in Water (23 Hours)	Arm 3: 23 mg Lenvatinib Suspension in Water (2 Hours)
Arm/Group Description	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (11 mg) suspension in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the administered lenvatinib (11 mg) capsules with 240 mL (8 fluid ounces) of water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 5 capsules of lenvatinib (11 mg total) in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 5 capsules of lenvatinib (11 mg total) in apple juice. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 2 capsules of lenvatinib (11 mg total) in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 2 capsules of lenvatinib (11 mg total) in apple juice. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (23 mg) suspension in water, which had been prepared 23 hours prior to administration. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (23 mg) suspension in water, which had been prepared 23 hours prior to administration. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.
Measure Participants	19	20	10	9	10	10	18	19
Mean (Standard Deviation) [hr·ng/mL]	1280 (437)	1290 (466)	987 (164)	1430 (668)	1290 (500)	971 (152)	2930 (887)	3130 (1010)

5. Primary Outcome

Title	Apparent Clearance (CL/F)
Description	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.
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)

Outcome Measure Data

Analysis Population Description

PK analysis set

Arm/Group Title	Arm 1: 11 mg Lenvatinib Suspension in Water	Arm 1: 11 mg Lenvatinib Capsule With Water	Arm 2: Lenvatinib 11 mg (Suspension of 5 Capsules in Water)	Arm 2: Lenvatinib 11 mg (Suspension of 5 Capsules in Juice)	Arm 2: Lenvatinib 11 mg (Suspension of 2 Capsules in Water)	Arm 2: Lenvatinib 11 mg (Suspension of 2 Capsules in Juice)	Arm 3: 23 mg Lenvatinib Suspension in Water (23 Hours)	Arm 3: 23 mg Lenvatinib Suspension in Water (2 Hours)
Arm/Group Description	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (11 mg) suspension in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the administered lenvatinib (11 mg) capsules with 240 mL (8 fluid ounces) of water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 5 capsules of lenvatinib (11 mg total) in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 5 capsules of lenvatinib (11 mg total) in apple juice. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 2 capsules of lenvatinib (11 mg total) in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 2 capsules of lenvatinib (11 mg total) in apple juice. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (23 mg) suspension in water, which had been prepared 23 hours prior to administration. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (23 mg) suspension in water, which had been prepared 23 hours prior to administration. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.
Measure Participants	19	20	10	8	10	10	17	19
Mean (Standard Deviation) [L/hour]	9.34 (4.36)	9.47 (4.45)	10.8 (1.73)	8.70 (3.44)	9.10 (3.07)	10.9 (1.61)	8.46 (2.65)	7.73 (2.19)

6. Primary Outcome

Title	Apparent Volume of Distribution (Vz/F)
Description	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).
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)

Outcome Measure Data

Analysis Population Description

PK analysis set

Arm/Group Title	Arm 1: 11 mg Lenvatinib Suspension in Water	Arm 1: 11 mg Lenvatinib Capsule With Water	Arm 2: Lenvatinib 11 mg (Suspension of 5 Capsules in Water)	Arm 2: Lenvatinib 11 mg (Suspension of 5 Capsules in Juice)	Arm 2: Lenvatinib 11 mg (Suspension of 2 Capsules in Water)	Arm 2: Lenvatinib 11 mg (Suspension of 2 Capsules in Juice)	Arm 3: 23 mg Lenvatinib Suspension in Water (23 Hours)	Arm 3: 23 mg Lenvatinib Suspension in Water (2 Hours)
Arm/Group Description	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (11 mg) suspension in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the administered lenvatinib (11 mg) capsules with 240 mL (8 fluid ounces) of water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 5 capsules of lenvatinib (11 mg total) in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 5 capsules of lenvatinib (11 mg total) in apple juice. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 2 capsules of lenvatinib (11 mg total) in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 2 capsules of lenvatinib (11 mg total) in apple juice. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (23 mg) suspension in water, which had been prepared 23 hours prior to administration. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (23 mg) suspension in water, which had been prepared 23 hours prior to administration. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.
Measure Participants	19	20	10	8	10	10	17	19
Mean (Standard Deviation) [Liters]	301 (159)	296 (123)	356 (74.0)	317 (131)	312 (122)	360 (103)	247 (95.7)	238 (122)

7. Primary Outcome

Title	Maximum Concentration (Cmax) of Lenvatinib in Plasma
Description	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 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)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) analysis set

Arm/Group Title	Arm 1: 11 mg Lenvatinib Suspension in Water	Arm 1: 11 mg Lenvatinib Capsule With Water	Arm 2: Lenvatinib 11 mg (Suspension of 5 Capsules in Water)	Arm 2: Lenvatinib 11 mg (Suspension of 5 Capsules in Juice)	Arm 2: Lenvatinib 11 mg (Suspension of 2 Capsules in Water)	Arm 2: Lenvatinib 11 mg (Suspension of 2 Capsules in Juice)	Arm 3: 23 mg Lenvatinib Suspension in Water (23 Hours)	Arm 3: 11 mg Lenvatinib Suspension in Water (2 Hours)
Arm/Group Description	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (11 mg) suspension in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the administered lenvatinib (11 mg) capsules with 240 mL (8 fluid ounces) of water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 5 capsules of lenvatinib (11 mg total) in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 5 capsules of lenvatinib (11 mg total) in apple juice. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	Arm 2 group description: On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 2 capsules of lenvatinib (11 mg total) in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 2 capsules of lenvatinib (11 mg total) in apple juice. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (23 mg) suspension in water, which had been prepared 23 hours prior to administration. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (11 mg) suspension in water, which had been prepared 23 hours prior to administration. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.
Measure Participants	19	20	10	9	10	10	18	19
Mean (Standard Deviation) [ng/mL]	133 (52.5)	126 (44.9)	115 (22.9)	150 (65.2)	138 (61.3)	105 (21.2)	358 (128)	375 (134)

8. Primary Outcome

Title	Time Prior to the First Measureable Concentration of Lenvatinib (Tlag)
Description	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 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)

Outcome Measure Data

Analysis Population Description

PK analysis set

Arm/Group Title	Arm 1: 11 mg Lenvatinib Suspension in Water	Arm 1: 11 mg Lenvatinib Capsule With Water	Arm 2: Lenvatinib 11 mg (Suspension of 5 Capsules in Water)	Arm 2: Lenvatinib 11 mg (Suspension of 5 Capsules in Juice)	Arm 2: Lenvatinib 11 mg (Suspension of 2 Capsules in Water)	Arm 2: Lenvatinib 11 mg (Suspension of 2 Capsules in Juice)	Arm 3: 23 mg Lenvatinib Suspension in Water (23 Hours)	Arm 3: 23 mg Lenvatinib Suspension in Water (2 Hours)
Arm/Group Description	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (11 mg) suspension in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the administered lenvatinib (11 mg) capsules with 240 mL (8 fluid ounces) of water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 5 capsules of lenvatinib (11 mg total) in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 5 capsules of lenvatinib (11 mg total) in apple juice. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 2 capsules of lenvatinib (11 mg total) in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 2 capsules of lenvatinib (11 mg total) in apple juice. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (23 mg) suspension in water, which had been prepared 23 hours prior to administration. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (23 mg) suspension in water, which had been prepared 23 hours prior to administration. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.
Measure Participants	19	20	10	9	10	10	18	19
Median (Full Range) [Hours]	0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00

9. Primary Outcome

Title	Time to Maximum Plasma Concentration (Tmax)
Description	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.
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)

Outcome Measure Data

Analysis Population Description

PK analysis set

Arm/Group Title	Arm 1: 11 mg Lenvatinib Suspension in Water	Arm 1: 11 mg Lenvatinib Capsule With Water	Arm 2: Lenvatinib 11 mg (Suspension of 5 Capsules in Water)	Arm 2: Lenvatinib 11 mg (Suspension of 5 Capsules in Juice)	Arm 2: Lenvatinib 11 mg (Suspension of 2 Capsules in Water)	Arm 2: Lenvatinib 11 mg (Suspension of 2 Capsules in Juice)	Arm 3: 23 mg Lenvatinib Suspension in Water (23 Hours)	Arm 3: 23 mg Lenvatinib Suspension in Water (2 Hours)
Arm/Group Description	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (11 mg) suspension in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the administered lenvatinib (11 mg) capsules with 240 mL (8 fluid ounces) of water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 5 capsules of lenvatinib (11 mg total) in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 5 capsules of lenvatinib (11 mg total) in apple juice. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 2 capsules of lenvatinib (11 mg total) in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 2 capsules of lenvatinib (11 mg total) in apple juice. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (23 mg) suspension in water, which had been prepared 23 hours prior to administration. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (23 mg) suspension in water, which had been prepared 23 hours prior to administration. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.
Measure Participants	19	20	10	9	10	10	18	19
Median (Full Range) [Hours]	3.00	3.00	2.52	3.00	2.50	2.00	2.00	2.00

10. Primary Outcome

Title	Terminal Elimination Phase Half-life (t1/2)
Description	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.
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)

Outcome Measure Data

Analysis Population Description

PK analysis set

Arm/Group Title	Arm 1: 11 mg Lenvatinib Suspension in Water	Arm 1: 11 mg Lenvatinib Capsule With Water	Arm 2: 11 mg Lenvatinib (Suspension of 5 Capsules in Water)	Arm 2: 11 mg Lenvatinib (Suspension of 5 Capsules in Juice)	Arm 2: 11 mg Lenvatinib (Suspension of 2 Capsules in Water)	Arm 2: 11 mg Lenvatinib (Suspension of 2 Capsules in Juice)	Arm 3: 23 mg Lenvatinib Suspension in Water (23 Hours)	Arm 3: 23 mg Lenvatinib Suspension in Water (2 Hours)
Arm/Group Description	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (11 mg) suspension in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the administered lenvatinib (11 mg) capsules with 240 mL (8 fluid ounces) of water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 5 capsules of lenvatinib (11 mg total) in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 5 capsules of lenvatinib (11 mg total) in apple juice. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 2 capsules of lenvatinib (11 mg total) in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 2 capsules of lenvatinib (11 mg total) in apple juice. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (23 mg) suspension in water, which had been prepared 23 hours prior to administration. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (23 mg) suspension in water, which had been prepared 2 hours prior to administration. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.
Measure Participants	19	20	10	9	10	10	18	19
Mean (Standard Deviation) [Hours]	22.7 (6.09)	22.4 (4.67)	23.2 (5.67)	25.5 (4.27)	24.1 (5.05)	23.1 (6.15)	20.4 (4.51)	21.5 (7.35)

11. Primary Outcome

Title	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Lenvatinib
Description	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.
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

Outcome Measure Data

Analysis Population Description

Safety Analysis Set was the group of subjects who received at least 1 dose of study drug and had at least 1 postdose safety assessment

Arm/Group Title	Arm 1: 11 mg Lenvatinib Suspension in Water	Arm 1: 11 mg Lenvatinib Capsule With Water	Arm 2: 11 mg Lenvatinib (Suspension of 5 Capsules in Water)	Arm 2: 11 mg Lenvatinib (Suspension of 5 Capsules in Juice)	Arm 2: 11 mg Lenvatinib (Suspension of 2 Capsules in Water)	Arm 2: 11 mg Lenvatinib (Suspension of 2 Capsules in Juice)	Arm 3: 23 mg Lenvatinib Suspension in Water (23 Hours)	Arm 3: 23 mg Lenvatinib Suspension in Water (2 Hours)
Arm/Group Description	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (11 mg) suspension in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the administered lenvatinib (11 mg) capsules with 240 mL (8 fluid ounces) of water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 5 capsules of lenvatinib (11 mg total) in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 5 capsules of lenvatinib (11 mg total) in apple juice. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 2 capsules of lenvatinib (11 mg total) in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 2 capsules of lenvatinib (11 mg total) in apple juice. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (23 mg) suspension in water, which had been prepared 23 hours prior to administration. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (23 mg) suspension in water, which had been prepared 2 hours prior to administration. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.
Measure Participants	19	20	10	9	10	10	18	19
TEAEs	4 40%	6 60%	1 20%	2 40%	4 80%	4 80%	3 30%	4 40%
Treatment-related TEAEs	4 40%	6 60%	0 0%	1 20%	2 40%	1 20%	3 30%	2 20%
Severe TEAEs	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Serious TEAEs	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

12. Secondary Outcome

Title	Summary Scores for Palatability of Lenvatinib
Description	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).
Time Frame	Treatment Period 1, Day 1 (Visit 2); Treatment Period 2, Day 8 (Visit 8)

Outcome Measure Data

Analysis Population Description

The Palatability Analysis Set was the group of subjects who received at least 1 dose of study drug and completed the visual analog scale (VAS) in at least one treatment period.

Arm/Group Title	Arm 1: 11 mg Lenvatinib Suspension in Water	Arm 1: 11 mg Lenvatinib Capsule With Water	Lenvatinib 11 mg (Suspension of 5 Capsules in Water)	Arm 2: Lenvatinib 11 mg (Suspension of 5 Capsules in Juice)	Arm 2: Lenvatinib 11 mg (Suspension of 2 Capsules in Water)	Arm 2: Lenvatinib 11 mg (Suspension of 2 Capsules in Juice)	Arm 3: 23 mg Lenvatinib Suspension in Water (23 Hours)	Arm 3: 23 mg Lenvatinib Suspension in Water (2 Hours)
Arm/Group Description	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (11 mg) suspension in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the administered lenvatinib (11 mg) capsules with 240 mL (8 fluid ounces) of water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 5 capsules of lenvatinib (11 mg total) in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 5 capsules of lenvatinib (11 mg total) in apple juice. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 2 capsules of lenvatinib (11 mg total) in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 2 capsules of lenvatinib (11 mg total) in apple juice. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (23 mg) suspension in water, which had been prepared 23 hours prior to administration. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (23 mg) suspension in water, which had been prepared 23 hours prior to administration. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.
Measure Participants	19	20	10	9	10	10	18	19
Flavor Score	3.0	4.0	3.0	4.0	2.5	4.0	2.0	2.0
Smell Score	4.0	4.0	3.5	4.0	4.0	4.0	3.0	3.0
Sweetness Score	3.0	3.0	3.0	4.0	2.0	4.0	2.0	2.0
Acidity Score	3.0	4.0	3.0	3.0	2.5	4.0	3.0	3.0
Saltiness Score	3.0	4.0	3.0	4.0	3.0	4.0	3.0	4.0
Bitterness Score	3.0	3.5	3.0	3.0	3.0	3.5	3.0	2.0
Texture or Mouth feel Score	3.0	3.5	2.0	4.0	3.0	4.0	2.0	2.0

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
Adverse Event Reporting Description	Treatment-emergent adverse events (TEAEs) and serious adverse events were reported. The Safety Analysis Set was the group of subjects who received at least 1 dose of study drug and had at least 1 postdose safety assessment
Arm/Group Title	Arm 1: 11 mg Lenvatinib Suspension in Water		Arm 1: 11 mg Lenvatinib Capsule With Water		Arm 2: 11 mg Lenvatinib (Suspension of 5 Capsules in Water)		Arm 2: 11 mg Lenvatinib (Suspension of 5 Capsules in Juice)		Arm 2: 11 mg Lenvatinib (Suspension of 2 Capsules in Water)		Arm 2: 11 mg Lenvatinib (Suspension of 2 Capsules in Juice)		Arm 3: 23 mg Lenvatinib Suspension in Water (23 Hours)		Arm 3: 23 mg Lenvatinib Suspension in Water (2 Hours)
Arm/Group Description	On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (11 mg) suspension in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.		On the administered lenvatinib (11 mg) capsules with 240 mL (8 fluid ounces) of water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.		On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 5 capsules of lenvatinib (11 mg total) in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.		On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 5 capsules of lenvatinib (11 mg total) in apple juice. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.		On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 2 capsules of lenvatinib (11 mg total) in water. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.		On the mornings of Days 1 and 8 following an overnight fast of at least 10 hours, participants were administered a suspension of 2 capsules of lenvatinib (11 mg total) in apple juice. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.		On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (23 mg) suspension in water, which had been prepared 23 hours prior to administration. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.		On the mornings of Days 1 and 8, following an overnight fast of at least 10 hours, participants were administered lenvatinib (23 mg) suspension in water, which had been prepared 2 hours prior to administration. No food was allowed for at least 4 hours post dose. Water was allowed ad libitum except for the period beginning 1 hour before and until 1 hour after lenvatinib administration. Treatments were administered at the same time on the 2 dosing days. On dosing days, all participants observed identical schedules with respect to fasting before dosing and timing of postdose meals.
All Cause Mortality
	Arm 1: 11 mg Lenvatinib Suspension in Water		Arm 1: 11 mg Lenvatinib Capsule With Water		Arm 2: 11 mg Lenvatinib (Suspension of 5 Capsules in Water)		Arm 2: 11 mg Lenvatinib (Suspension of 5 Capsules in Juice)		Arm 2: 11 mg Lenvatinib (Suspension of 2 Capsules in Water)		Arm 2: 11 mg Lenvatinib (Suspension of 2 Capsules in Juice)		Arm 3: 23 mg Lenvatinib Suspension in Water (23 Hours)		Arm 3: 23 mg Lenvatinib Suspension in Water (2 Hours)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/20 (0%)		0/10 (0%)		0/9 (0%)		0/10 (0%)		0/10 (0%)		0/18 (0%)		0/19 (0%)
Serious Adverse Events
	Arm 1: 11 mg Lenvatinib Suspension in Water		Arm 1: 11 mg Lenvatinib Capsule With Water		Arm 2: 11 mg Lenvatinib (Suspension of 5 Capsules in Water)		Arm 2: 11 mg Lenvatinib (Suspension of 5 Capsules in Juice)		Arm 2: 11 mg Lenvatinib (Suspension of 2 Capsules in Water)		Arm 2: 11 mg Lenvatinib (Suspension of 2 Capsules in Juice)		Arm 3: 23 mg Lenvatinib Suspension in Water (23 Hours)		Arm 3: 23 mg Lenvatinib Suspension in Water (2 Hours)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/20 (0%)		0/10 (0%)		0/9 (0%)		0/10 (0%)		0/10 (0%)		0/18 (0%)		0/19 (0%)
Other (Not Including Serious) Adverse Events
	Arm 1: 11 mg Lenvatinib Suspension in Water		Arm 1: 11 mg Lenvatinib Capsule With Water		Arm 2: 11 mg Lenvatinib (Suspension of 5 Capsules in Water)		Arm 2: 11 mg Lenvatinib (Suspension of 5 Capsules in Juice)		Arm 2: 11 mg Lenvatinib (Suspension of 2 Capsules in Water)		Arm 2: 11 mg Lenvatinib (Suspension of 2 Capsules in Juice)		Arm 3: 23 mg Lenvatinib Suspension in Water (23 Hours)		Arm 3: 23 mg Lenvatinib Suspension in Water (2 Hours)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/19 (21.1%)		6/20 (30%)		1/10 (10%)		2/9 (22.2%)		4/10 (40%)		4/10 (40%)		3/18 (16.7%)		4/19 (21.1%)
Gastrointestinal disorders
Diarrhoea	0/19 (0%)		1/20 (5%)		0/10 (0%)		0/9 (0%)		0/10 (0%)		1/10 (10%)		0/18 (0%)		0/19 (0%)
Flatulence	1/19 (5.3%)		0/20 (0%)		0/10 (0%)		0/9 (0%)		0/10 (0%)		0/10 (0%)		0/18 (0%)		0/19 (0%)
Abdominal pain	0/19 (0%)		0/20 (0%)		0/10 (0%)		0/9 (0%)		0/10 (0%)		0/10 (0%)		0/18 (0%)		1/19 (5.3%)
Nausea	0/19 (0%)		0/20 (0%)		0/10 (0%)		0/9 (0%)		0/10 (0%)		0/10 (0%)		1/18 (5.6%)		0/19 (0%)
Vomiting	0/19 (0%)		0/20 (0%)		0/10 (0%)		0/9 (0%)		0/10 (0%)		0/10 (0%)		1/18 (5.6%)		0/19 (0%)
General disorders
Asthenia	1/19 (5.3%)		1/20 (5%)		0/10 (0%)		0/9 (0%)		0/10 (0%)		0/10 (0%)		0/18 (0%)		0/19 (0%)
Chills	0/19 (0%)		1/20 (5%)		0/10 (0%)		0/9 (0%)		0/10 (0%)		0/10 (0%)		0/18 (0%)		0/19 (0%)
Fatigue	1/19 (5.3%)		1/20 (5%)		0/10 (0%)		0/9 (0%)		0/10 (0%)		0/10 (0%)		0/18 (0%)		0/19 (0%)
Feeling hot	0/19 (0%)		1/20 (5%)		0/10 (0%)		0/9 (0%)		0/10 (0%)		0/10 (0%)		0/18 (0%)		0/19 (0%)
Pain	0/19 (0%)		0/20 (0%)		0/10 (0%)		0/9 (0%)		0/10 (0%)		0/10 (0%)		1/18 (5.6%)		0/19 (0%)
Investigations
Blood bilirubin abnormal	0/19 (0%)		1/20 (5%)		0/10 (0%)		0/9 (0%)		0/10 (0%)		0/10 (0%)		0/18 (0%)		0/19 (0%)
Blood glucose decreased	0/19 (0%)		0/20 (0%)		0/10 (0%)		0/9 (0%)		1/10 (10%)		1/10 (10%)		0/18 (0%)		0/19 (0%)
Blood phosphorus decreased	0/19 (0%)		0/20 (0%)		0/10 (0%)		0/9 (0%)		1/10 (10%)		0/10 (0%)		0/18 (0%)		0/19 (0%)
Blood pressure increased	0/19 (0%)		0/20 (0%)		0/10 (0%)		0/9 (0%)		1/10 (10%)		0/10 (0%)		0/18 (0%)		0/19 (0%)
Heart rate decreased	0/19 (0%)		0/20 (0%)		0/10 (0%)		1/9 (11.1%)		0/10 (0%)		1/10 (10%)		0/18 (0%)		0/19 (0%)
Urine analysis abnormal	0/19 (0%)		0/20 (0%)		0/10 (0%)		0/9 (0%)		1/10 (10%)		1/10 (10%)		0/18 (0%)		0/19 (0%)
Blood lactate dehydrogenase increased	0/19 (0%)		0/20 (0%)		0/10 (0%)		0/9 (0%)		0/10 (0%)		0/10 (0%)		1/18 (5.6%)		0/19 (0%)
Blood triglycerides increased	0/19 (0%)		0/20 (0%)		0/10 (0%)		0/9 (0%)		0/10 (0%)		0/10 (0%)		0/18 (0%)		1/19 (5.3%)
Liver function test abnormal	0/19 (0%)		0/20 (0%)		0/10 (0%)		0/9 (0%)		0/10 (0%)		0/10 (0%)		1/18 (5.6%)		0/19 (0%)
White blood cell count decreased	0/19 (0%)		0/20 (0%)		0/10 (0%)		0/9 (0%)		0/10 (0%)		0/10 (0%)		0/18 (0%)		1/19 (5.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/19 (0%)		1/20 (5%)		0/10 (0%)		0/9 (0%)		0/10 (0%)		0/10 (0%)		0/18 (0%)		0/19 (0%)
Nervous system disorders
Headache	1/19 (5.3%)		1/20 (5%)		0/10 (0%)		1/9 (11.1%)		0/10 (0%)		0/10 (0%)		2/18 (11.1%)		0/19 (0%)
Hypoaesthesia	0/19 (0%)		1/20 (5%)		0/10 (0%)		0/9 (0%)		0/10 (0%)		0/10 (0%)		0/18 (0%)		0/19 (0%)
Psychiatric disorders
Euphoric mood	0/19 (0%)		1/20 (5%)		0/10 (0%)		0/9 (0%)		0/10 (0%)		0/10 (0%)		0/18 (0%)		0/19 (0%)
Insomnia	0/19 (0%)		0/20 (0%)		0/10 (0%)		0/9 (0%)		0/10 (0%)		0/10 (0%)		1/18 (5.6%)		0/19 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/19 (0%)		1/20 (5%)		0/10 (0%)		0/9 (0%)		0/10 (0%)		0/10 (0%)		1/18 (5.6%)		1/19 (5.3%)
Oropharyngeal pain	0/19 (0%)		1/20 (5%)		0/10 (0%)		0/9 (0%)		0/10 (0%)		0/10 (0%)		0/18 (0%)		0/19 (0%)
Epistaxis	0/19 (0%)		0/20 (0%)		0/10 (0%)		0/9 (0%)		0/10 (0%)		0/10 (0%)		0/18 (0%)		1/19 (5.3%)
Skin and subcutaneous tissue disorders
Erythema	0/19 (0%)		0/20 (0%)		1/10 (10%)		0/9 (0%)		0/10 (0%)		0/10 (0%)		0/18 (0%)		0/19 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.