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)

NCT ID: NCT01253187

Last Updated: 2013-08-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-10-31
• Study Completion Date: 2007-09-30

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

Conditions

Contraception

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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)

Group Type: EXPERIMENTAL

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

Intervention Type: 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 0.02mg/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 \[MTHF-Ca\])

Group Type: EXPERIMENTAL

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

Intervention Type: 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 Ca 0.451 mg (Metafolin)

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

Group Type: EXPERIMENTAL

L-5-MTHF 0.451mg (Metafolin)

Intervention Type: 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.

Interventions

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

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.

Intervention Type: DRUG

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

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.

Intervention Type: DRUG

L-5-MTHF 0.451mg (Metafolin)

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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 38 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Bayer

INDUSTRY

Sponsor Role: lead

Responsible Party

Bayer Healthcare AG

Principal Investigators

Bayer Study Director

Role: STUDY_DIRECTOR

Bayer

Locations

Dinox B.V.

Groningen, , Netherlands

Countries

Netherlands

References

Blode H, Klipping C, Richard F, Trummer D, Rohde B, Diefenbach K. Bioequivalence study of an oral contraceptive containing ethinylestradiol/drospirenone/levomefolate calcium relative to ethinylestradiol/drospirenone and to levomefolate calcium alone. Contraception. 2012 Feb;85(2):177-84. doi: 10.1016/j.contraception.2011.05.015. Epub 2011 Jul 19.

Reference Type: RESULT

PMID: 22067789 (View on PubMed)

Other Identifiers

2005-003049-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

309664

Identifier Type: OTHER

Identifier Source: secondary_id

91460

Identifier Type: -

Identifier Source: org_study_id