Assessment of the Pharmacodynamic Effect on Plasma Folate and Red Blood Cell Folate and Comparison of the Folate Metabolites During the 24 Weeks of Treatment (Yasmin + Metafolin Versus Yasmin + Folic Acid) Followed by a 20 Week Elimination Phase of Folate
Condition: Contraception
Intervention: EE 0.03 mg/DRSP 3 mg/Metafolin + folic acid placebo; EE 0.03 mg/DRSP 3 mg (Yasmin) + folic acid
Intervention description: Combination EE/DRSP/ Metafolin [0.030 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP) + 0.451 mg Metafolin] given orally in a cyclic regimen for 24 weeks (6 cycles) in combination with folic acid placebo tablets (encapsulated). Each treatment cycle consisting of once daily hormone and Metafolin treatment for 21-days followed by once daily hormone free, Metafolin only regimen for 7 days. This phase was followed by 20 weeks (5 cycles) folate elimination phase consisting of oral administration of Yasmin alone.; Yasmin [0.030 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP)] in combination with folic acid tablets 0.4 mg (encapsulated), given orally in a cyclic regimen for 24 weeks (6 cycles). Each treatment cycle providing once daily hormone and folic acid treatment for 21 days followed by once daily hormone free, folic acid only regimen for 7 days (encapsulated). This phase was followed by 20 weeks (5 cycles) folate elimination phase consisting of oral administration of Yasmin alone.
Intervention MeSH terms: Folic Acid; Vitamin B Complex; Drospirenone
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 172.0
Sex: Female
Minimum age: 18 Years
Maximum age: 40 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The purpose of this study is to examine and compare the uptake of levomefolate calcium
      (Metafolin, a registered vitamin supplement) and folic acid in the body during 24 weeks of
      treatment with a following folate elimination phase of 20 weeks in healthy volunteers seeking
      contraception. Yasmin (oral contraceptive containing drospirenone and ethinylestradiol) was
      co-administered over the entire period of 44 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age 18-40 years.

          -  RBC folate > 317 nmol/L and < 906 nmol/L.

          -  At least 1 menstruation during the last 3 months before screening with the exception
             of women using progestin-only methods (injection, implant) or progestin-releasing
             intrauterine system (IUS).

          -  Negative pregnancy test at screening and at admission into the study.

          -  Healthy as confirmed by medical history and physical examination.

          -  Body mass index (BMI) of 18.5-30.0 kg/m2 .

          -  Volunteers that smoke less than 10 cigarettes per day can be included up to the age of
             30 years.

          -  Adequate vitamin B12 status defined as plasma B12 concentrations ≥ 110 pmol/L.

        Exclusion Criteria:

          -  Regular intake of folic acid defined as > 100 μg folic acid/day in vitamin supplements
             or fortified food during the last 4 months.

          -  Treatment with the following medications, which has the potential of interfering with
             folate metabolism: cholestyramine, methotrexate, trimethoprim, sulfasalazine,
             salicylic acid, cotrimoxazol, antacids or antiepileptic drugs.

          -  Pregnancy, lactation (at least three cycles have to follow delivery, abortion, or
             lactation before start of treatment)

          -  Vascular or metabolic disease including existing or previous arterial thromboembolic
             diseases (myocardial infarction, stroke), existing or previous venous thromboembolic
             diseases (deep vein thrombosis, pulmonary embolism), and any condition which could
             increase the risk to suffer any of the above mentioned disorders

          -  Any disease or condition that could compromise the function of the body systems and
             could result in altered absorption, excessive accumulation, impaired metabolism, or
             altered excretion of the study medication.

          -  Any disease that may worsen under hormonal treatment or might interfere with the
             conduct of the study or the interpretation of the results (e.g., herpes gestationis or
             idiopathic icterus pregnancy; middle-ear deafness ; Sydenham's chorea, porphyria,
             disturbances in the bile flow.

          -  Liver diseases: Presence or history of severe hepatic diseases including benign or
             malignant tumors