Investigation of Bioequivalence of Ethinylestradiol (EE) and Drospirenone (DRSP) in Two Different Tablet Formulations: YAZ and YAZ + Levomefolate Calcium (Metafolin) & L-5-MTHF in Two Different Tablet Formulations: Levomefolate Calcium (Metafolin) and YAZ + Levomefolate Calcium (Metafolin)

Bayer

Status and phase: Completed; Phase 1

Conditions: Contraception

Treatments: Drug: EE 0.02 mg/DRSP 3 mg/L-5-MTHF Ca 0.451 mg (EE20/DRSP/L-5-MTHF Ca); Drug: EE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300); Drug: L-5-MTHF 0.451mg (Metafolin)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01253187

2005-003049-15 (EudraCT Number)

91460

309664 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is examine and compare the uptake of YAZ (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 YAZ in the body, in healthy volunteers not using hormonal contraception

Enrollment: 44 patients

Sex: Female

Ages: 18 to 38 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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44 participants in 3 patient groups

EE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300)

Experimental group

Description:

single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP)

Treatment:

Drug: EE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300)

EE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca)

Experimental group

Description:

single oral administration of 1 film-coated SHT04532B tablet, containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP) + 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[MTHF-Ca\])

Treatment:

Drug: EE 0.02 mg/DRSP 3 mg/L-5-MTHF Ca 0.451 mg (EE20/DRSP/L-5-MTHF Ca)

L-5-MTHF Ca 0.451 mg (Metafolin)

Experimental group

Description:

single oral administration of 1 coated SHT04532C tablet, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[MTHF-Ca\])

Treatment:

Drug: L-5-MTHF 0.451mg (Metafolin)