Bioequivalence Study of Levothyroxine Sodium Tablets 100 mcg
Bioequivalence Study of Levothyroxine Sodium Tablets 100 mcg
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.
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 pharmacopeial 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 (6 x 100 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.
Inclusion Criteria:

 -  Signed Informed Consent

 -  Healthy volunteers according to antecedents, clinical evaluation, biochemical tests
 and other complimentary tests

 -  Sex: both (male and female, homogenously distributed)

 -  Age: 18 to 50 years old

 -  BMI: 18 to 30 kg/m2

 -  Non smokers from at least 3 months

 Exclusion Criteria:

 -  History of liver disease, kidney disease or conditions of psychiatric origin.

 -  History of drug or alcohol abuse in the last two years.

 -  Ingestion of other drugs the 2 weeks prior to the start of the study.

 -  History of seizure disorders, depressive disorders, cardiovascular diseases,
 hematological, metabolic, vesicular or other, that the Principal Investigator judges
 clinically significant.

 -  Abnormal electrocardiogram (EKG).

 -  Hypersensitivity to Levothyroxine sodium or to excipients (from formulations to test).

 -  Positive HIV test; hepatitis B and C.

 -  Positive urine drug dose of abuse.

 -  Having participated in another research study in the last 6 months.

 -  Having donated blood within the 3 months prior to the start of the study.

 -  Clinically significant abnormal laboratory test results.

 -  Abnormal results outside the reference values for thyroid function (T3, T4, TSH,
 anti-TPO antibodies).

 -  Female volunteers who are breastfeeding during the study period.

 -  Positive beta-HCG test in female volunteers.

 -  Volunteers who must start a scheduled medical or pharmacological treatment outside the
 this Protocol.

 -  Volunteers who do not maintain the conditions of fasting and food intake in the
 pre-established schedules.

 -  Volunteers who do not avoid the intake of coffee, tea, grapefruit, cola and / or
 alcoholic beverages during the 48 h preceding the study.

 -  Volunteers on a special diet in the last 28 days (eg vegetarian diet, etc.).

 -  Volunteers with clinically significant allergies to food, medication, etc.

 -  Non-cooperative volunteers.