Investigation of Bioequivalence of Ethinylestradiol (EE) and Drospirenone (DRSP) in Two Different Tablet Formulations: Yasmin and Yasmin + Levomefolate Calcium (Metafolin) & L-5-MTHF in Two Different Tablet Formulations: Levomefolate Calcium (Metafolin) and Yasmin + Levomefolate Calcium (Metafolin)
Condition: Contraception
Intervention: EE 0.03 mg/DRSP 3 mg (Yasmin, BAY86-5131); EE 0.03mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE30/DRSP/L-5-MTHF Ca); L-5-MTHF Ca 0.451 mg (Metafolin)
Intervention description: single oral administration of 1 coated tablet SH T470FA (Yasmin, film-coated tablets with ethinylestradiol (EE) as free steroid), containing 0.030 mg EE + 3 mg drospirenone (DRSP); single oral administration of 1 coated tablet SH T04532A (film-coated tablet with ethinylestradiol (EE) as clathtrate), containing 0.030 mg EE + 3 mg drospirenone (DRSP) + 0.451 mg Metafolin; single oral administration of 1 coated tablet SH T04532C, containing 0.451 mg Metafolin
Intervention MeSH terms: Tetrahydrofolates; Drospirenone
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 48.0
Sex: Female
Minimum age: 18 Years
Maximum age: 38 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The purpose of this study is to examine and compare the uptake of Yasmin (oral contraceptive
      containing drospirenone and ethinylestradiol) with or without levomefolate calcium
      (Metafolin, a registered vitamin supplement) in the body and to examine and compare the
      uptake of levomefolate calcium with or without Yasmin in the body, in healthy volunteers not
      using hormonal contraception.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Healthy female volunteer

          -  Age: 18 - 38 years inclusive

          -  Body mass index (BMI)1: ≥ 19 and < 28 kg/m²

          -  Regular cyclic menstrual periods at screening OR when using combined oral
             contraceptives during the recruitment period reporting of natural cyclic menstrual
             periods prior to their use

          -  Willingness to use non-hormonal methods of contraception during the complete trial OR
             previous tubal ligation

        Exclusion Criteria:

          -  incompletely cured pre-existing diseases for which it can be assumed that the
             absorption, distribution, metabolism, excretion and effect of the study drugs will not
             be normal

          -  known or suspected sex-steroid influenced malignancies

          -  endometrial hyperplasia; genital bleeding of unknown origin; uterus myomatosus

          -  known or suspected tumors of the liver and pituitary

          -  presence or history of severe hepatic disease as long as liver function values have
             not returned to normal

          -  severe renal insufficiency or acute renal failure

          -  thrombophlebitis, venous / arterial thromboembolic diseases; presence or history of
             prodromi of a thrombosis

          -  other conditions that increase susceptibility to thromboembolic diseases

          -  known neuropsychiatric diseases, especially known or suspected epilepsy, and/ or
             deficient status of folate or vitamin B12

          -  use of any other medication within 2 cycles before first study drug administration
             which could affect the study aim

          -  use of potassium sparing drugs; use of folic acid containing supplements or medicines
             or use of any medication within 2 cycles before first study drug administration known
             to interfere with folate metabolism

          -  inadequate folate and/or Vitamin B12 status , clinically relevant deviations in red
             cell folate concentrations