A Randomized, Three-treatment, Three-period, Six-sequence Crossover, Single-center, Bioequivalence Study to Evaluate the Impact of Varying Crystalline Polymorph Forms for the Commercial Oral Capsule Formulation of 10-mg Lenvatinib in Healthy Volunteers

Eisai Inc.0 个研究点目标入组 60 人开始时间: 2013年7月最近更新: 2019年3月14日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: Eisai Inc.
入组人数: 60
主要终点: Area Under the Concentration-Time Curve From Zero Time (Predose) Extrapolated to Infinite Time (AUC(0-inf))

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者记录与标识符相似试验

研究概览

简要总结

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.

详细描述

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%.

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Crossover
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 55 Years（Adult）
性别: All
接受健康志愿者: 是

入选标准

•Healthy male and female participants age greater than or equal to 18 years and less than or equal to 55 years old
•Nonsmokers or smokers who smoke no more than 10 cigarettes per day
•BMI greater than or equal to 18 and less than or equal to 32 kg/m2 at Screening
•Females must not be lactating or pregnant at Screening or Baseline (as documented by a negative beta-human chorionic gonadotropin)
•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)
•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.
•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.
•Provide written informed consent

排除标准

•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
•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
•Any history of GI surgery that may affect pharmacokinetic profiles of lenvatinib e.g., hepatectomy, nephrotomy, digestive organ resection known at Screening or Baseline
•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
•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.
•A prolonged QTcF interval (QTcF greater than 450 ms) demonstrated on ECG at Screening or Baseline
•Known history of clinically significant drug allergy at Screening or Baseline
•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
•Known to be human immunodeficiency virus positive at Screening
•Active viral hepatitis (A, B, or C) as demonstrated by positive serology at Screening
•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
•Intake of grapefruit or grapefruit-containing beverages or food within 72 hours prior to dosing
•Intake of medications known to be strong inhibitors or inducers of CYP450 3A4 metabolizing enzymes within 2 weeks prior to dosing
•Currently enrolled in another clinical trial or used any investigational drug or device within 30 days preceding informed consent
•Receipt of blood products within 4 weeks, or donation of blood within 8 weeks, or donation of plasma within 1 week of dosing
•Engagement in strenuous exercise within 2 weeks prior to check-in (e.g., marathon runners, weight lifters)
•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

研究组 & 干预措施

Sequence A:

Experimental

Participants will receive one dose of Treatment 1 followed by one dose of Treatment 2, then one dose of Treatment 3