Bioequivalence of Two Levothyroxine Tablet Formulations in Healthy Indian Volunteers
Condition: Hypothyroidism
MeSH terms: Hypothyroidism
Study type: Interventional
Phase: Phase 4

Summary: 
      GSK markets a drug called levothyroxine or T4 that is used to treat patients with
      hypothyroidism. Till date, the active drug substance or active pharmaceutical ingredient
      (API) for levothyroxine tablets marketed in India has been obtained from a particular source.
      GSK India proposes to change the source of the API from the existing source to a new source.
      Some patients may experience a change in clinical effect when switched from one formulation
      to another. Therefore this study is being done to understand whether a change in API in
      levothyroxine tablet has any impact on the clinical effect of the drug.

      The purpose of this study is to:

      See how quickly the levothyroxine tablet from the new source (single dose of 600mcg) enters
      the bloodstream, is distributed in the body, broken down and removed compared to the
      levothyroxine tablet from the existing source (single dose of 600mcg).

      Study the effect of single 600mcg doses of levothyroxine tablet from new source and
      levothyroxine tablet from existing source on TSH level in the blood.

      Study the safety and side effects of single 600mcg doses of levothyroxine tablet from new
      source and levothyroxine tablet from existing source.
    

Detailed description: 
      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. Till date, the active pharmaceutical
      ingredient (API) for levothyroxine tablets marketed in India has been sourced from company 1.
      GSK India proposes to change the source of the API from the existing source (company 1) to to
      new source (company 2). In view of this change in the source of API, it is essential to
      determine whether it has any impact on drug product performance based on pharmacokinetic (PK)
      measures of total serum T4 and total serum T3 of the to-be-marketed formulation of
      levothyroxine (test formulation from company 2, Treatment A) relative to the formulation
      currently in the market (reference formulation from company 1, Treatment B).

      This will be a single-center, open-label, two-period, two-treatment, two-sequence,
      randomized, single-dose, crossover study. 26 healthy adult males will be randomized to
      receive a single dose (6 x 100mcg tablets = 600mcg) 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 35 day washout between the two treatment periods.

      The study will be conducted at BA/BE facility after approval from an independent ethics
      committee. Subjects will have a screening visit within 21 days prior to the first dose of
      study drug, two treatment periods with each containing a single dose of study drug, followed
      by 48 hours of serial PK sample collection. Subjects will check out of the unit on Day 3 (at
      7am) after collection of the 48 hour PK sample. The subject will be instructed to return for
      the next treatment period or for the final follow-up visit, as appropriate. The final
      follow-up visit will occur 35 days after the last dose of study drug. Subjects will be
      assigned to each of the two treatments randomly as per the randomization schedule.
    

Intervention name(s): Levothyroxine; Levothyroxine
Intervention type(s): Drug; Drug
Intervention description(s): Single dose of 600mcg of test formulation of levothyroxine administered in dosing period 1 or 2.; Single dose of 600mcg of reference formulation of levothyroxine administered in dosing period 1 or 2.
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)