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)

NCT01253187 | Completed Phase 1 Results

• 3 other identifiers: 914602005-003049-15309664
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (8)

• 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

• 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

• 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

• Mean Area Under the Concentration-time Curve From Administration to the Last Measurement [AUC(0-tlast)] 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

• 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

• 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

• 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

• 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

Secondary Outcomes (4)

• 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

Study Arms (3)

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

EXPERIMENTAL

single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP)

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

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

EXPERIMENTAL

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 \[MTHF-Ca\])

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

L-5-MTHF Ca 0.451 mg (Metafolin)

EXPERIMENTAL

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

Drug: L-5-MTHF 0.451mg (Metafolin)

Interventions

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 (YAZ, BAY86-5300)

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.

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

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.

L-5-MTHF Ca 0.451 mg (Metafolin)

Eligibility Criteria

• Age: 18 Years - 38 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (1)

Dinox B.V.

Groningen, 9713GZ, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 22067789 RESULT

MeSH Terms

Interventions

drospirenone; drospirenone and ethinyl estradiol combination; 5-methyltetrahydrofolate; levomefolate calcium

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: Bayer HealthCare AG

clinical-trials-contact@bayerhealthcare.com

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: December 2, 2010
• First Posted: December 3, 2010
• Study Start: October 1, 2006
• Primary Completion: September 1, 2007
• Study Completion: September 1, 2007
• Last Updated: August 7, 2013
• Results First Posted: May 9, 2011

Record last verified: 2013-08

Locations

NL (1)