Bioequivalence Study: 2 mg Estradiol Valerate (EV) and 3 mg Dienogest (DNG) Without and With Levomefolate Calcium

Open-label, Randomized, Cross-over Study to Investigate the Bioequivalence of Estradiol Valerate (EV), Dienogest (DNG) and Levomefolate Calcium After Single Oral Administration of a Tablet Formulation Containing 2 mg Estradiol Valerate and 3 mg Dienogest Without and With 0.451 mg Levomefolate Calcium and a Tablet Formulation Containing 0.451 mg Levomefolate Calcium in 42 Healthy Postmenopausal Women

Investigation of the bioequivalence (BE) of Estradiol Valerate (EV) and Dienogest (DNG) after administration of one film-coated tablet containing 2 mg Estradiol Valerate, 3 mg Dienogest and 0.451 mg Levomefolate calcium as compared to one film-coated tablet containing 2 mg Estradiol Valerate,3 mg Dienogest.Investigation of the bioequivalence of levomefolate calcium after administration of one film-coated tablet containing 2 mg Estradiol Valerate, 3 mg Dienogest and 0.451 mg Levomefolate calcium as compared to one film-coated tablet containing 0.451 mg levomefolate calcium

Inclusion Criteria:

• Healthy postmenopausal women, age: 45-75 years with body mass index between ≥18 and ≤30 kg/m2. Post-menopausal state revealed by: medical history, and hormone analyses in serum: estradiol ≤20 pg/mL and in women <60 years old: follicle-stimulating hormone ≥ 40 IU/L at screening

Exclusion Criteria:

• Contraindications for use of combined (Estradiolvalerate/Dienogest) contraceptive (e.g.history of venous/arterial thromboembolic disease)
• Regular intake of medication
• Clinically relevant findings (ECG, blood pressure, physical and gynaecological examination, laboratory examination)
• Smoking