Crossover Study to Evaluate the Relative Bioavailability and Palatability of a Lenvatinib Suspension Compared to the Capsule Formulation in Adult Healthy Volunteers
Condition: Healthy Volunteers
Intervention: Lenvatinib
Intervention description: 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.
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: Bioavailability of Lenvatinib suspension; Palatability of Lenvatinib suspension; Lenvatinib; Lenvima; E7080; Capsule formulation; Healthy volunteers

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.
    

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 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