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Trial record 14 of 100 for:    DROSPIRENONE AND ETHINYL ESTRADIOL

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)

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ClinicalTrials.gov Identifier: NCT01253174
Recruitment Status : Completed
First Posted : December 3, 2010
Results First Posted : May 9, 2011
Last Update Posted : August 7, 2013
Sponsor:
Information provided by:
Bayer

Tracking Information
First Submitted Date  ICMJE December 2, 2010
First Posted Date  ICMJE December 3, 2010
Results First Submitted Date  ICMJE December 9, 2010
Results First Posted Date  ICMJE May 9, 2011
Last Update Posted Date August 7, 2013
Study Start Date  ICMJE August 2006
Actual Primary Completion Date July 2007   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 18, 2011)
  • 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.
  • 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
  • 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.
  • Mean Area Under the Concentration-time Curve (AUC) 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
  • 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.
  • 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.
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 2, 2010)
  • Mean Maximum Concentration (Cmax) of EE Incl. Bioequivalence (BE) Evaluation [ Time Frame: 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 [ Time Frame: up to 96 hours after administration ]
  • Mean Maximum Concentration (Cmax) of DRSP Incl. Bioequivalence (BE) Evaluation [ Time Frame: up to 168 hours after administration ]
  • Mean Area Under the Concentration-time Curve (AUC) of DRSP Incl. Bioequivalence (BE) Evaluation [ Time Frame: up to 168 hours after administration ]
  • Mean Maximum Concentration (Cmax) of L-5-methyl-THF (Baseline Corrected) Incl. Bioequivalence (BE) Evaluation [ Time Frame: 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 [ Time Frame: 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 ]
  • 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 ]
Change History Complete list of historical versions of study NCT01253174 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 18, 2011)
  • 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
  • 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 ]
    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 ]
    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 ]
    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
Original Secondary Outcome Measures  ICMJE
 (submitted: December 2, 2010)
  • Time to Reach Maximum Concentration (Tmax) of EE [ Time Frame: 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 ]
  • Time to Reach Maximum Concentration (Tmax) of DRSP [ Time Frame: up to 168 hours after administration ]
  • Time to reach maximum concentration (Tmax) of L-5-methyl-THF (baseline uncorrected) [ Time Frame: up to 12 hours after administration ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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)
Official Title  ICMJE 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
Brief 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Contraception
Intervention  ICMJE
  • 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)
  • 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
  • Drug: L-5-MTHF Ca 0.451 mg (Metafolin)
    single oral administration of 1 coated tablet SH T04532C, containing 0.451 mg Metafolin
Study Arms  ICMJE
  • 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)
    Intervention: Drug: EE 0.03 mg/DRSP 3 mg (Yasmin, BAY86-5131)
  • 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])
    Intervention: Drug: EE 0.03mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE30/DRSP/L-5-MTHF Ca)
  • 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])
    Intervention: Drug: L-5-MTHF Ca 0.451 mg (Metafolin)
Publications * 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 levomefolate calcium alone. Clin Drug Investig. 2012 Oct 1;32(10):673-84. doi: 10.2165/11635280-000000000-00000.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 2, 2010)
48
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE July 2007
Actual Primary Completion Date July 2007   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 38 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01253174
Other Study ID Numbers  ICMJE 91457
2005-001913-16 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Head Clinical Pharmacology, Bayer Healthcare AG
Study Sponsor  ICMJE Bayer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bayer Study Director Bayer
PRS Account Bayer
Verification Date August 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP