An Open-label, Single-dose, Randomized, 4-period, 2-sequence, Fully Replicated Crossover, Single-center Phase I Study to Assess Bioequivalence in Healthy Participants Between Euthyrox® Tablets Manufactured at Merck Nantong Versus Euthyrox® Tablets Manufactured at Merck Darmstadt Administered Orally as 12 Tablets of 50 μg
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- Maximum Observed Serum Concentration, Adjusted for Baseline (Cmax[adj]) of Total Thyroxine (T4)
研究概览
简要总结
The purpose of this study is to demonstrate bioequivalence (BE) between Euthyrox® tablets manufactured at Merck Nantong (Test Euthyrox) versus the tablets manufactured at Merck Darmstadt (Reference Euthyrox).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 59 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants have a body weight within 45 to 75 kilogram (kg) for females and 55 to 85 kg for males and Body mass index (BMI) within the range 19.0 to 26.0 kilograms per meter square (kg/m^2)
- •Non-smoker for at least 3 months
- •Contraceptive use by males or females will be consistent with any local regulations on contraception methods for those participating in clinical studies
- •Capable of giving signed informed consent
- •Total and free Thyroxine (T4), total and free Triiodothyronine (T3) and Thyroid-stimulating Hormone (TSH) must be within normal ranges at Screening
- •Ability to understand the purposes and risks of the study
- •Other protocol defined inclusion criteria could apply
排除标准
- •Participants with history or presence of tumors of the pituitary gland or hypothalamus, thyroid or adrenal gland dysfunction or cardiac disease
- •Participants with a concurrent medical condition known to interfere with the absorption or metabolism of thyroid hormones
- •History or presence of relevant liver diseases or hepatic dysfunction. Participants with gall bladder removal
- •Participants taking medications known to affect thyroid hormone metabolism, for example, oral contraceptives, hormonal implants, parenteral hormones, anabolic steroids, androgens, etcetera
- •Use of any investigational device within 60 days prior to first dose administration
- •Pregnant or breastfeeding a child
- •Participant has smoked within the 3 months prior to Screening
- •High fiber consumption within 24 hours before dosing in each period
- •Participants with positive results from serology examination for Syphilis, Hepatitis B surface antigen, Hepatitis C Virus or Human Immunodeficiency Virus
- •Participants with any clinically relevant abnormality in the safety laboratory parameters
- •Participants with positive test for drugs of abuse (including alcohol) at Screening and on Day -1 of each period (urine)
- •Other protocol defined exclusion criteria could apply
研究组 & 干预措施
Sequence 1:Test Euthyrox®, then Reference Euthyrox®, then Test Euthyrox®, then Reference Euthyrox®
Participants will receive single oral dose of Test Euthyrox® on in treatment period 1, followed by single oral dose of Reference Euthyrox® in treatment period 2, followed by single oral dose of Test Euthyrox® in treatment period 3, followed by single oral dose of Reference Euthyrox in treatment period 4. Participants will remain resident until Day 4 for each treatment period and there will be a washout period of 53 days between each treatment period.
干预措施: Test Euthyrox® (Drug)
Sequence 1:Test Euthyrox®, then Reference Euthyrox®, then Test Euthyrox®, then Reference Euthyrox®
Participants will receive single oral dose of Test Euthyrox® on in treatment period 1, followed by single oral dose of Reference Euthyrox® in treatment period 2, followed by single oral dose of Test Euthyrox® in treatment period 3, followed by single oral dose of Reference Euthyrox in treatment period 4. Participants will remain resident until Day 4 for each treatment period and there will be a washout period of 53 days between each treatment period.
干预措施: Reference Euthyrox® (Drug)
Sequence 2:Reference Euthyrox®, then Test Euthyrox®, then Reference Euthyrox®, then Test Euthyrox®
Participants will receive single oral dose of Reference Euthyrox® in treatment period 1, followed by single oral dose of Test Euthyrox® in treatment period 2, followed by single oral dose of Reference Euthyrox® in treatment period 3, followed by single oral dose of Test Euthyrox® in treatment period 4. Participants will remain resident until Day 4 for each treatment period and there will be a washout period of 53 days between each treatment period.
干预措施: Test Euthyrox® (Drug)
Sequence 2:Reference Euthyrox®, then Test Euthyrox®, then Reference Euthyrox®, then Test Euthyrox®
Participants will receive single oral dose of Reference Euthyrox® in treatment period 1, followed by single oral dose of Test Euthyrox® in treatment period 2, followed by single oral dose of Reference Euthyrox® in treatment period 3, followed by single oral dose of Test Euthyrox® in treatment period 4. Participants will remain resident until Day 4 for each treatment period and there will be a washout period of 53 days between each treatment period.
干预措施: Reference Euthyrox® (Drug)
结局指标
主要结局
Maximum Observed Serum Concentration, Adjusted for Baseline (Cmax[adj]) of Total Thyroxine (T4)
时间窗: Pre-dose up to 72 hours post-dose
Baseline-Corrected Area Under the Serum Concentration-Time Curve (AUC) from Time Zero to 72 hours Post-dose (AUC0-72,adj) of Total Thyroxine (T4)
时间窗: Pre-dose up to 72 hours post-dose
次要结局
- Serum Concentrations of Total Thyroxine (T4) and Triiodothyronine (T3)(Pre-dose up to 72 hours post-dose)
- Safety Profile as Assessed by Occurrence of Severity of Treatment-emergent Adverse Events (TEAEs), Laboratory Variables, Vital Signs and 12-Lead Electrocardiogram (ECG) Measurements(Baseline up to 10 months)