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

Contraception Clinical Trial

Official title:

Open-label, Randomized, Three-fold Crossover Study to Investigate the Bioequivalence of Two Different Tablet Formulations Containing 0.03 mg Ethinylestradiol (EE) and 3 mg Drospirenone (DRSP) Without [SH T470FA] and With [SH T04532A] 0.451 mg Metafolin®, and to Investigate the Bioequivalence of Two Different Tablet Formulations Containing 0.451 mg Metafolin® Without [SH T04532C] and With 0.03 mg EE/ 3 mg DRSP [SH T04532A] in 42 Healthy Young Women

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01253174
• Other study ID #: 91457
• Secondary ID: 2005-001913-16
• Status: Completed
• Phase: Phase 1
• First received: December 2, 2010
• Last updated: August 1, 2013
• Start date: August 2006
• Est. completion date: July 2007

Study information

• Verified date: August 2013
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: July 2007
• Est. primary completion date: July 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 38 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Contraception

Intervention

Drug:
• EE 0.03 mg/DRSP 3 mg (Yasmin, BAY86-5131)
single oral administration of 1 coated tablet SH T470FA (Yasmin, film-coated tablets with ethinylestradiol (EE) as free steroid), containing 0.030 mg EE + 3 mg drospirenone (DRSP)
• EE 0.03mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE30/DRSP/L-5-MTHF Ca)
single oral administration of 1 coated tablet SH T04532A (film-coated tablet with ethinylestradiol (EE) as clathtrate), containing 0.030 mg EE + 3 mg drospirenone (DRSP) + 0.451 mg Metafolin
• L-5-MTHF Ca 0.451 mg (Metafolin)
single oral administration of 1 coated tablet SH T04532C, containing 0.451 mg Metafolin

Locations

Country	Name	City	State
Germany	Scope International	Hamburg

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Wiesinger H, Eydeler U, Richard F, Trummer D, Blode H, Rohde B, Diefenbach K. Bioequivalence evaluation of a folate-supplemented oral contraceptive containing ethinylestradiol/drospirenone/levomefolate calcium versus ethinylestradiol/drospirenone and levo — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Maximum Concentration (Cmax) of EE Incl. Bioequivalence (BE) Evaluation	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.	up to 96 hours after administration	No
Primary	Mean Area Under the Concentration-time Curve From Administration to the Last Measurement [AUC(0-tlast)] of EE Incl. Bioequivalence (BE) Evaluation	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	up to 96 hours after administration	No
Primary	Mean Maximum Concentration (Cmax) of DRSP Incl. Bioequivalence (BE) Evaluation	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.	up to 168 hours after administration	No
Primary	Mean Area Under the Concentration-time Curve (AUC) of DRSP Incl. Bioequivalence (BE) Evaluation	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	up to 168 hours after administration	No
Primary	Mean Maximum Concentration (Cmax) of L-5-methyl-THF (Baseline Corrected) Incl. Bioequivalence (BE) Evaluation	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.	up to 12 hours after administration	No
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	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.	up to 12 hours after administration	No
Primary	Mean Maximum Concentration (Cmax) of L-5-methyl-THF (Baseline Uncorrected) Incl. Bioequivalence (BE) Evaluation	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.	up to 12 hours after administration	No
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	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.	up to 12 hours after administration	No
Secondary	Time to Reach Maximum Concentration (Tmax) of EE	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	up to 96 hours after administration	No
Secondary	Mean Area Under the Concentration-time Curve From Administration up to 72h AUC(0-72h) of DRSP	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	up to 72 hours after administration	No
Secondary	Time to Reach Maximum Concentration (Tmax) of DRSP	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	up to 168 hours after administration	No
Secondary	Time to Reach Maximum Concentration (Tmax) of L-5-methyl-THF	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	up to 12 hours after administration	No

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