Bioequivalence Study to Evaluate the Impact of Varying Crystalline Polymorph Forms for the Commercial Oral Capsule Formulation of 10-mg Lenvatinib in Healthy Volunteers

The study will consist of 2 phases: Prerandomization and Randomization. The Prerandomization
Phase will have 2 periods: Screening and Baseline. The Randomization Phase will consist of
three 6-day long Treatment Periods with each Treatment Period separated by a 1-day long
Baseline. Sixty participants will be evenly randomized to 1 of 6 possible treatment sequences
(A, B, C, D, E, or F). The 3 treatments vary by the level of crystalline polymorph Type-C
present in the drug product batch used in each arm, respectively: Treatment 1 - low Type-C
crystal level less than 12%; Treatment 2 - reference Type-C crystal level 12% to 26%; and
Treatment 3 - high Type-C crystal level greater than 26%.

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

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. Females must not be lactating or pregnant at Screening or Baseline (as documented by a
negative beta-human chorionic gonadotropin)

5. 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
(i.e., bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all
with surgery at least 1 month before dosing)

6. 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 (e.g., 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.

7. Male participants must have had a successful vasectomy (confirmed azoospermia) or they
and their female partners must meet the criteria above (i.e., 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.

8. Provide written informed consent

Exclusion Criteria:

1. Clinically significant illness that requires medical treatment within 8 weeks of
Screening or a clinically significant infection that requires medical treatment within
4 weeks of dosing

2. Evidence of disease that may influence the outcome of the study within 4 weeks prior
to dosing, e.g., psychiatric disorders and disorders of the gastrointestinal 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 GI surgery that may affect pharmacokinetic profiles of lenvatinib e.g.,
hepatectomy, nephrotomy, digestive organ resection known at Screening or Baseline

4. Any clinically abnormal symptom or organ impairment found by medical history, physical
examinations, vital signs, ECG findings, or laboratory test results that require
medical treatment at Screening or Baseline

5. Blood pressure measurements of greater than 150/90 mm Hg. Confirmation should be
obtained by performing three measurements (at least 5 minutes apart) to yield a mean
value. Participants may be enrolled if they are on a stable dose of a single
antihypertensive drug at least 30 days prior to the first dose of study drug and do
not intend to change the dose or drug during the study.

6. A prolonged QTcF interval (QTcF greater than 450 ms) demonstrated on ECG at Screening
or Baseline

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

8. Known history of food allergies or presently experiencing significant seasonal or
perennial allergy at Screening or Baseline or with a known history of sensitivity to
any of the components of the test products

9. Known to be human immunodeficiency virus 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 a positive urine drug test at Screening or Baseline

12. Intake of grapefruit or grapefruit-containing beverages or food within 72 hours prior
to dosing

13. Intake of medications known to be strong inhibitors or inducers of CYP450 3A4
metabolizing enzymes within 2 weeks prior to dosing

14. Currently enrolled in another clinical trial or used any investigational drug or
device within 30 days preceding informed consent

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

16. Engagement in strenuous exercise within 2 weeks prior to check-in (e.g., marathon
runners, weight lifters)

17. Any condition that would make the participant, in the opinion of the investigator or
sponsor unsuitable for the study or not likely to complete the study for any reason