Bioavailability of Levonorgestrel and Ethinyl Estradiol Tablets 15.0 mg/0.03 mg With Regards to Reference Product
Condition: Bioequivalence
Study type: Interventional
Phase: Phase 1

Summary: 
      This Pivotal study will investigate the bioavailability in women of 2 tablet formulations
      containing Levonorgestrel 15.0 mg and Ethinyl estradiol 0.03 mg. The Pivotal study will be
      performed at a single site with 30 subjects. Participants will take 2 tablets of the test
      product and reference product in 2 periods and 2 sequences (either test after reference or
      reference after test). There will be a washout of at least 14 days between each study period.
    

Detailed description: 
      The primary objective of the study is to investigate the relative bioavailability of
      Levonorgestrel and Ethinyl estradiol of 2 tablet formulations with Levonorgestrel 15.0 mg and
      Ethinyl estradiol 0.03 mg and to demonstrate bioequivalence of both formulations in terms of
      rate and extent of absorption:

        -  Test Product: Product manufactured by Laboratorios Andrómaco S.A.

        -  Reference Product: Microgynon [Trademark], product of Bayer AG, Germany. The 90%
           confidence intervals for the intra-subject coefficient of variation (Test versus
           Reference Product) for the main pharmacokinetic parameters área under the plasma
           concentration-time curve from time zero to time t (AUC0-t) and from time zero to 72
           hours (AUC0-72), and maximum plasma concentration (Cmax) for total Levonorgestrel and
           Ethinyl estradiol will be determined.

      Participants will be confined in the study site for approximately 36 hours during each study
      period (for 12 hours pre-dosing and for 24 hours post dosing) during which pharmacokinetic
      (PK) blood samples will be obtained. 16 blood samples will be taken up to 24 hours after the
      administration in each period. Participants will return to the site to provide additional
      blood samples at 48 h, and 72 h postdose.

      The washout period between the two study periods will be at least 14 days. The samples from
      each participant will be analyzed with 2 methods of highperformance liquid
      chromatography-tandem mass spectrometry bioanalytical assays to quantify total Levonorgestrel
      and Ethinyl estradiol in plasma.

      The safety objective is to evaluate the tolerability of both formulations in women by
      collecting adverse events.
    

Intervention name(s): Levonorgestrel 15.0 mg and Ethinyl estradiol 0.03 mg Test Drug; Levonorgestrel 15.0 mg and Ethinyl estradiol 0.03 mg Reference Product
Intervention type(s): Drug; Drug
Intervention description(s): Bioequivalence; Bioequivalence
Other intervention name(s): Investigational Medicinal Product; Microgynon CD (Trademark)
Intervention MeSH terms: Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Levonorgestrel; Ethinyl Estradiol; Ethinyl estradiol, levonorgestrel drug combination; Estradiol; Polyestradiol phosphate
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science