BE of Euthyrox® Tablets (Merck Nantong Versus Merck Darmstadt Sites)

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: Test Euthyrox®
* Drug: Reference Euthyrox®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence 1:Test Euthyrox®, then Reference Euthyrox®, then Test Euthyrox®, then Reference Euthyrox®<br>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. | Drug: Test Euthyrox®<br>* Participants will receive single oral dose of Test Euthyrox® either in treatment period 1, 2, 3 or 4.<br>* Other names: Levothyroxine sodium;Drug: Reference Euthyrox®<br>* Participants will receive single oral dose of Reference Euthyrox® either in treatment period 1, 2, 3 or 4.<br>* Other names: Levothyroxine sodium;|
| Experimental: Sequence 2:Reference Euthyrox®, then Test Euthyrox®, then Reference Euthyrox®, then Test Euthyrox®<br>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. | Drug: Test Euthyrox®<br>* Participants will receive single oral dose of Test Euthyrox® either in treatment period 1, 2, 3 or 4.<br>* Other names: Levothyroxine sodium;Drug: Reference Euthyrox®<br>* Participants will receive single oral dose of Reference Euthyrox® either in treatment period 1, 2, 3 or 4.<br>* Other names: Levothyroxine sodium;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Serum Concentration, Adjusted for Baseline (Cmax[adj]) of Total Thyroxine (T4) |  | 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) |  | Pre-dose up to 72 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Euthyrox®, Bioequivalence, Thyroid-Stimulating Hormone, Thyroxine