Bioequivalence Study of Levothyroxine Sodium Tablets 150 mcg

Study Overview
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Brief Summary
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The objective of this study is to establish the bioequivalence of two levothyroxine formulations through the estimation of T4 levels in serum samples after baseline correction, according to Food and Drugs Administration (FDA), World Health Organization (WHO) and Colombian National Vigilance Institute for Drugs and Food (INVIMA) guidelines.

Detailed Description
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Levothyroxine (T4) is used to treat patients with hypothyroidism and may often result in lifelong therapy. Its physiologically active metabolite is tri-iodothyronine (T3). Levothyroxine is also endogenously produced in the body. Since small changes in levothyroxine administration (e.g. change in brand or formulation) can cause significant changes in serum thyroid stimulating hormone (TSH) concentrations, precise and accurate TSH control is critical to avoid potential adverse iatrogenic effects. Tecnoquimicas modified its Levothyroxine tablets formulation in order to comply with new pharmacopeical specifications. It will then evaluate the impact on drug product performance based on pharmacokinetic (PK) measures of total serum T4 and total serum T3 of the new formulation of levothyroxine (Test formulation) relative to the reference formulation from Merck (Reference formulation) This will be a single-center, open-label, two-period, two-treatment, two-sequence, randomized, single-dose, crossover study. 80 healthy adults will be randomized to receive a single dose (4 x 150 mcg tablets = 600 mcg) of the test formulation of levothyroxine and reference formulation of levothyroxine separately in each treatment period. There will be two treatment sequences (AB, BA) and a 42 day washout between the two treatment periods.

Official Title
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Bioequivalence Study of Levothyroxine Sodium Tablets 150 mcg

Conditions
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Healthy

Intervention / Treatment
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* Drug: Drug Levothyroxine 150 mcg
* Drug: Drug Eutirox 150 mcg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and Women from 18 to 50 years old Diagnosed as healthy after a clinical examination BMI from 18 to 30 kg/m2 Not smoking for at least 3 months To sign the informed consent Not having participated in a similar study for at least 4 months Exclusion Criteria: Renal, cardiac immunological, dermatological, endocrine, gastrointestinal, neurological or psychiatric condition Hematologic disorders, specially anemia and polycythemia Permanent or temporal pharmacological therapy, prescribed or not Smoking for the last 3 months Alcohol drinker more than once a week Drug abuse Drug hypersensitivity Angioedema or anaphylaxis history Pregnancy or breast-feeding HIV o Hepatitis B diagnosed Blood donor in the past 30 days

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test Formulation of Levothyroxine<br>Levothyroxine sodium tablets 150 mcg Single dose of 600 mcg administered in dosing period 1 or 2 | Drug: Drug Levothyroxine 150 mcg<br>* Administration of a 600 mcg levothyroxine dose<br>|
| Active Comparator: Reference formulation of Levothyroxine<br>Eutirox 150 mcg Single dose of 600 mcg administered in dosing period 1 or 2 | Drug: Drug Eutirox 150 mcg<br>* Administration of a 600 mcg levothyroxine dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| (AUC) Area Under the Curve 0-48 for T4 | -0.5, -0.25, 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 and 48 hours | From 0 to 48 hours | 
| Cmax for T4 | -0.5, -0.25, 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 and 48 hours | From 0 to 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC 0-48 for T3 | -0.5, -0.25, 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 and 48 hours | From 0 to 48 hours | 
| Cmax for T3 |  | From 0 to 48 hours | 
| Tmax | -0.5, -0.25, 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 and 48 hours | From 0 to 48 hours | 
| Kel | -0.5, -0.25, 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 and 48 hours | From 0 to 48 hours |