- ICH GCP
- US Clinical Trials Registry
- Clinical Trial 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)
August 1, 2013 updated by: Bayer
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
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
Study Overview
Status
Completed
Conditions
Study Type
Interventional
Enrollment (Actual)
44
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Groningen, Netherlands, 9713GZ
- Dinox B.V.
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 38 years (ADULT)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
Female
Description
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 Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: CROSSOVER
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: 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)
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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.
|
EXPERIMENTAL: 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])
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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.
|
EXPERIMENTAL: 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])
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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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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up to 96 hours after administration
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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.
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up to 12 hours after administration
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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.
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up to 12 hours after administration
|
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.
|
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
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.
|
up to 12 hours after administration
|
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
|
up to 96 hours after administration
|
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
|
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
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
|
up to 168 hours after administration
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
up to 96 hours after administration
|
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
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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
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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
|
up to 168 hours after administration
|
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
|
up to 12 hours after administration
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
October 1, 2006
Primary Completion (ACTUAL)
September 1, 2007
Study Completion (ACTUAL)
September 1, 2007
Study Registration Dates
First Submitted
December 2, 2010
First Submitted That Met QC Criteria
December 2, 2010
First Posted (ESTIMATE)
December 3, 2010
Study Record Updates
Last Update Posted (ESTIMATE)
August 7, 2013
Last Update Submitted That Met QC Criteria
August 1, 2013
Last Verified
August 1, 2013
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 91460
- 2005-003049-15 (EUDRACT_NUMBER)
- 309664 (OTHER: Company Internal)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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