Bioequivalence Study to Evaluate the Impact of Varying Crystalline Polymorph Forms for the Commercial Oral Capsule Formulation of 10-mg Lenvatinib in Healthy Volunteers
Condition: Healthy Volunteers
Intervention: Lenvatinib 10 mg
Intervention description: Treatment 1: low Type-C crystal level <12%
Treatment 2: reference* Type-C crystal level 12% to 26%
Treatment 3: high Type-C crystal level >26%
Intervention MeSH terms: Lenvatinib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 60.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Bioequivalence; Lenvatinib; Healthy Volunteers; Lenvima; E7080

Summary:

      This will be a randomized, single dose, open-label, three-treatment period crossover study in
      healthy participants to determine whether 2 test lots of 10-mg capsules that vary by the
      level of lenvatinib Type-C crystal are bioequivalent to a reference lot of 10-mg capsules.
    

Eligibility criteria:

        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