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)
This study has been completed.
Sponsor:
Bayer
Information provided by:
Bayer
ClinicalTrials.gov Identifier:
NCT01253174
First received: December 2, 2010
Last updated: August 3, 2012
Last verified: August 2012
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Contraception |
Drug: EE 0.03 mg/DRSP 3 mg (Yasmin, BAY86-5131) Drug: EE 0.03mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE30/DRSP/L-5-MTHF Ca) Drug: L-5-MTHF Ca 0.451 mg (Metafolin) |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Bio-equivalence Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Treatment |
| 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 |
Resource links provided by NLM:
Drug Information available for:
Ethinyl Estradiol
Calcium Gluconate
Drospirenone
Levomefolate calcium
U.S. FDA Resources
Further study details as provided by Bayer:
Primary Outcome Measures:
- Mean Maximum Concentration (Cmax) of EE Incl. Bioequivalence (BE) Evaluation [ Time Frame: up to 96 hours after administration ] [ Designated as safety issue: No ]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.
- 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 ] [ Designated as safety issue: No ]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
- Mean Maximum Concentration (Cmax) of DRSP Incl. Bioequivalence (BE) Evaluation [ Time Frame: up to 168 hours after administration ] [ Designated as safety issue: No ]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.
- Mean Area Under the Concentration-time Curve (AUC) of DRSP Incl. Bioequivalence (BE) Evaluation [ Time Frame: up to 168 hours after administration ] [ Designated as safety issue: No ]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
- Mean Maximum Concentration (Cmax) of L-5-methyl-THF (Baseline Corrected) Incl. Bioequivalence (BE) Evaluation [ Time Frame: up to 12 hours after administration ] [ Designated as safety issue: No ]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.
- 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 ] [ Designated as safety issue: No ]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.
- Mean Maximum Concentration (Cmax) of L-5-methyl-THF (Baseline Uncorrected) Incl. Bioequivalence (BE) Evaluation [ Time Frame: up to 12 hours after administration ] [ Designated as safety issue: No ]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.
- 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 ] [ Designated as safety issue: No ]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 Outcome Measures:
- Time to Reach Maximum Concentration (Tmax) of EE [ Time Frame: up to 96 hours after administration ] [ Designated as safety issue: No ]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
- 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 ] [ Designated as safety issue: No ]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
- Time to Reach Maximum Concentration (Tmax) of DRSP [ Time Frame: up to 168 hours after administration ] [ Designated as safety issue: No ]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
- Time to Reach Maximum Concentration (Tmax) of L-5-methyl-THF [ Time Frame: up to 12 hours after administration ] [ Designated as safety issue: No ]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
| Enrollment: | 48 |
| Study Start Date: | August 2006 |
| Study Completion Date: | July 2007 |
| Primary Completion Date: | July 2007 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: EE 0.03 mg/DRSP 3 mg (Yasmin, BAY86-5131)
single oral administration of 1 film-coated SHT470FA tablet (Yasmin with ethinylestradiol (EE) as free steroid), containing 0.030 mg EE + 3 mg drospirenone (DRSP)
|
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)
|
|
Experimental: EE 0.03mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE30/DRSP/L-5-MTHF Ca)
single oral administration of 1 film-coated SHT04532A tablet (with ethinylestradiol (EE) as clathtrate), containing 0.030 mg EE + 3 mg drospirenone (DRSP) + 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium [MTHF-Ca])
|
Drug: 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
|
|
Active Comparator: L-5-MTHF Ca 0.451 mg (Metafolin)
single oral administration of 1 coated tablet SHT04532C, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium [MTHF-Ca])
|
Drug: L-5-MTHF Ca 0.451 mg (Metafolin)
single oral administration of 1 coated tablet SH T04532C, containing 0.451 mg Metafolin
|
Eligibility| Ages Eligible for Study: | 18 Years to 38 Years |
| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | Yes |
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
Contacts and Locations More Information
Additional Information:
No publications provided
| Responsible Party: | Head Clinical Pharmacology, Bayer Healthcare AG |
| ClinicalTrials.gov Identifier: | NCT01253174 History of Changes |
| Other Study ID Numbers: | 91457, 2005-001913-16 |
| Study First Received: | December 2, 2010 |
| Results First Received: | December 9, 2010 |
| Last Updated: | August 3, 2012 |
| Health Authority: | Germany: Federal Institute for Drugs and Medical Devices |
Additional relevant MeSH terms:
|
Ethinyl Estradiol Drospirenone Drospirenone and ethinyl estradiol combination Estrogens Hormones Hormones, Hormone Substitutes, and Hormone Antagonists |
Physiological Effects of Drugs Pharmacologic Actions Aldosterone Antagonists Hormone Antagonists Reproductive Control Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on May 16, 2013