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Completed

NCT Number: NCT01253187

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)

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

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Key information

Conditions

Contraception

Age range

18 year–38 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 1

Primary location

Dinox B.V.

Groningen, 9713GZ, Netherlands

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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

Drug

Treatment group A: Single 1 film-coated tablet (Ethinylestradiol [EE] 0.02mg / Drospirenone [DRSP] 3mg) taken orally under fasting condition at intervals of at least one menstrual cycle.

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

Drug

Treatment group B: Single 1 film-coated tablet (Ethinylestradiol [EE] 0.02mg / Drospirenone [DRSP] 3mg / L-5-methyltetrahydrofolate [L-5-MTHF] 0.451mg) taken orally under fasting condition at intervals of at least one menstrual cycle.

L-5-MTHF 0.451mg (Metafolin)

Drug

Treatment group C: Single 1 coated tablet (L-5-methyltetrahydrofolate [L-5-MTHF] 0.451mg) taken orally under fasting condition at intervals of at least one menstrual cycle.

Primary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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

  1. Time to Reach Maximum Concentration (Tmax) of EE

    Time frame: up to 96 hours after administration

    Tmax refers to the time after dosing when a drug attains its highest measurable concentration (Cmax). It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content

  2. Mean Area Under the Concentration-time Curve From Administration up to 72h AUC(0-72h) of DRSP

    Time frame: up to 72 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

  3. Time to Reach Maximum Concentration (Tmax) of DRSP

    Time frame: up to 168 hours after administration

    Tmax refers to the time after dosing when a drug attains its highest measurable concentration (Cmax). It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content

  4. Time to Reach Maximum Concentration (Tmax) of L-5-methyl-THF

    Time frame: up to 12 hours after administration

    Tmax refers to the time after dosing when a drug attains its highest measurable concentration (Cmax). It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content

Sponsors and collaborators

Lead sponsor

Bayer

Industry

Registry information

Official study title

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

Important dates

Study start
2006
Primary completion
2007
Study completion
2007
First posted
Dec 3, 2010
Registry last updated
Aug 7, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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