Clinical trial NCT02792829: Crossover Study to Evaluate the Relative Bioavailability and Palatability of a Lenvatinib Suspension Compared to the Capsule Formulation in Adult Healthy Volunteers
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Bioavailability of Lenvatinib suspension
Palatability of Lenvatinib suspension
Lenvatinib
Lenvima
E7080
Capsule formulation
Healthy volunteers
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2016-06-08
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Area Under the Plasma Concentration-Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC(0-t))
timeFrame: 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)
measure: Area Under the Plasma Concentration-Time Curve From Zero to Infinity (AUC(0-inf))
timeFrame: 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)
measure: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC(0-24))
timeFrame: Treatment Period 1: Predose up to 24 hours post dose
measure: Area Under the Plasma Concentration-Time Curve From Zero to 72 Hours (AUC(0-72))
timeFrame: Treatment Period 1: Predose up to 72 hours postdose
measure: Apparent Clearance (CL/F)
timeFrame: 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)
measure: Apparent Volume of Distribution (Vz/F)
timeFrame: 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)
measure: Maximum Concentration (Cmax) of Lenvatinib in Plasma
timeFrame: 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)
measure: Time Prior to the First Measureable Concentration of Lenvatinib (Tlag)
timeFrame: 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)
measure: Time to Maximum Plasma Concentration (Tmax)
timeFrame: 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)
measure: Terminal Elimination Phase Half-life (t1/2)
timeFrame: 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)
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Lenvatinib
timeFrame: From date of first dose of study treatment to date of last dose of study treatment, up to approximately 2 months 10 days
Secondary outcomes:
measure: Summary Scores for Palatability of Lenvatinib
timeFrame: Treatment Period 1, Day 1 (Visit 2); Treatment Period 2, Day 8 (Visit 8)
Other outcomes:
Locations:
city: Las Vegas
country: United States
state: Nevada
Study officials:
References: