Open-label, Randomized, Three-fold Crossover Study to Investigate the Bioequivalence of Two Different Tablet Formulations Containing 0.02 mg Ethinylestradiol (EE) and 3 mg Drospirenone (DRSP) Without [SH T00186D] and With [SH T04532B] 0.451 mg L-mefolinate (Metafolin), and to Investigate the Bioequivalence of Two Different Tablet Formulations Containing 0.451 mg L-mefolinate (Metafolin) Without [SH T04532C] and With 0.02 mg EE/ 3 mg DRSP [SH T04532B] in 42 Healthy Young Women
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Bayer
- Enrollment
- 44
- Locations
- 1
- Primary Endpoint
- Mean Maximum Concentration (Cmax) of EE Incl. Bioequivalence (BE) Evaluation
Study Overview
Brief Summary
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
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 38 Years (Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- Yes
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
Arms & Interventions
EE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300)
single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP)
Intervention: EE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300) (Drug)
EE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca)
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])
Intervention: EE 0.02 mg/DRSP 3 mg/L-5-MTHF Ca 0.451 mg (EE20/DRSP/L-5-MTHF Ca) (Drug)
L-5-MTHF Ca 0.451 mg (Metafolin)
single oral administration of 1 coated SHT04532C tablet, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium [MTHF-Ca])
Intervention: L-5-MTHF 0.451mg (Metafolin) (Drug)
Outcomes
Primary Outcomes
Mean Maximum Concentration (Cmax) of EE Incl. Bioequivalence (BE) Evaluation
Time Frame: up to 96 hours after administration
Cmax refers to the highest measured drug concentration which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample
Mean Area Under the Concentration-time Curve From Administration to the Last Measurement [AUC(0-tlast)] of EE Incl. Bioequivalence (BE) Evaluation
Time Frame: up to 96 hours after administration
The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample
Mean Maximum Concentration (Cmax) of DRSP Incl. Bioequivalence (BE) Evaluation
Time Frame: up to 168 hours after administration
Cmax refers to the highest measured drug concentration which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample
Mean Area Under the Concentration-time Curve From Administration to the Last Measurement [AUC(0-tlast)] of DRSP Incl. Bioequivalence (BE) Evaluation
Time Frame: up to 168 hours after administration
The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample
Mean Maximum Concentration (Cmax) of L-5-methyl-THF (Baseline Corrected) Incl. Bioequivalence (BE) Evaluation
Time Frame: up to 12 hours after administration
The baseline corrected Cmax is a measure of the highest measured drug concentration provided solely by the treatment after subtracting endogenous L-5-methyl-THF level. It is obtained by collecting a series of blood samples, measuring the concentrations of L-5-methyl-THF in each sample and by subtracting the pre-treatment concentration.
Mean Area Under the Concentration-time Curve From Administration to the Last Measurement [AUC(0-tlast)] of L-5-methyl-THF (Baseline Corrected) Incl. Bioequivalence (BE) Evaluation
Time Frame: up to 12 hours after administration
The baseline corrected AUC is a measure of the systemic drug exposure provided by the treatment excluding the endogenous L-5-methyl-THF level. It is obtained by collecting a series of blood samples, measuring the concentrations of L-5-methyl-THF in each sample and by subtracting the pre-treatment concentration.
Mean Maximum Concentration (Cmax) of L-5-methyl-THF (Baseline Uncorrected) Incl. Bioequivalence (BE) Evaluation
Time Frame: up to 12 hours after administration
The baseline uncorrected Cmax is a measure of the highest measured drug concentration including the endogenous L-5-methyl-THF level. It is obtained by collecting a series of blood samples and measuring the concentrations of L-5-methyl-THF in each sample.
Mean Area Under the Concentration-time Curve From Administration to the Last Measurement [AUC(0-tlast)] of L-5-methyl-THF (Baseline Uncorrected) Incl. Bioequivalence (BE) Evaluation
Time Frame: up to 12 hours after administration
The baseline uncorrected AUC is a measure of the systemic drug exposure provided by the treatment including the endogenous L-5-methyl-THF level. It is obtained by collecting a series of blood samples and measuring the concentrations of L-5-methyl-THF in each sample.
Secondary Outcomes
- Time to Reach Maximum Concentration (Tmax) of EE(up to 96 hours after administration)
- Mean Area Under the Concentration-time Curve From Administration up to 72h AUC(0-72h) of DRSP(up to 72 hours after administration)
- Time to Reach Maximum Concentration (Tmax) of DRSP(up to 168 hours after administration)
- Time to Reach Maximum Concentration (Tmax) of L-5-methyl-THF(up to 12 hours after administration)