Phase 1
Completed N=44
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)
Source: ClinicalTrials.gov NCT01253187 ↗Enrolled (actual)
44
Serious AEs
0.0%
Results posted
May 2011
Primary outcomePrimary: Mean Maximum Concentration (Cmax) of EE Incl. Bioequivalence (BE) Evaluation — 39.6; 41.9 pg/mL
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
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Mean Maximum Concentration (Cmax) of EE Incl. Bioequivalence (BE) Evaluation |
39.6; 41.9 | — |
| PRIMARY Mean Area Under the Concentration-time Curve From Administration to the Last Measurement [AUC(0-tlast)] of EE Incl. Bioequivalence (BE) Evaluation |
358; 370 | — |
| PRIMARY Mean Maximum Concentration (Cmax) of DRSP Incl. Bioequivalence (BE) Evaluation |
25.4; 26.7 | — |
| PRIMARY Mean Area Under the Concentration-time Curve From Administration to the Last Measurement [AUC(0-tlast)] of DRSP Incl. Bioequivalence (BE) Evaluation |
386; 383 | — |
| PRIMARY Mean Maximum Concentration (Cmax) of L-5-methyl-THF (Baseline Corrected) Incl. Bioequivalence (BE) Evaluation |
44.3; 44.2 | — |
| PRIMARY 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 |
214; 217 | — |
| PRIMARY Mean Maximum Concentration (Cmax) of L-5-methyl-THF (Baseline Uncorrected) Incl. Bioequivalence (BE) Evaluation |
57.9; 57.7 | — |
| PRIMARY 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 |
370; 370 | — |
| SECONDARY Time to Reach Maximum Concentration (Tmax) of EE |
1.50; 1.52 | — |
| SECONDARY Mean Area Under the Concentration-time Curve From Administration up to 72h AUC(0-72h) of DRSP |
350; 344 | — |
| SECONDARY Time to Reach Maximum Concentration (Tmax) of DRSP |
2.00; 2.00 | — |
| SECONDARY Time to Reach Maximum Concentration (Tmax) of L-5-methyl-THF |
0.50; 0.50 | — |
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
Data sourced from ClinicalTrials.gov (NCT01253187). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.