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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)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01253187
First Posted: December 3, 2010
Last Update Posted: August 7, 2013
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by:
Bayer
Results First Submitted: December 9, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: Contraception
Interventions: Drug: EE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300)
Drug: EE 0.02 mg/DRSP 3 mg/L-5-MTHF Ca 0.451 mg (EE20/DRSP/L-5-MTHF Ca)
Drug: L-5-MTHF 0.451mg (Metafolin)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Healthy young women, aged 18 – 38 years inclusive, who were nonsmokers were enrolled from 20 October 2006 to 13 September 2007 at one center in Germany.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
77 female volunteers were screened according to the inclusion and exclusion criteria to determine that the volunteer was in a good state of health and appropriate for inclusion in the study, and 44 volunteers were randomized at one center.

Reporting Groups
  Description
Treatment Sequence A: YAZ, EE20/DRSP/L-5-MTHF Ca, Metafolin YAZ for Period 1; EE20/DRSP/L-5-MTHF Ca for Period 2; Metafolin for Period 3. YAZ: single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP) / 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]) / Metafolin: single oral administration of 1 coated SHT04532C tablet, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium [MTHF-Ca]).
Treatment Sequence B: YAZ, Metafolin, EE20/DRSP/L-5-MTHF Ca YAZ for Period 1; Metafolin for Period 2; EE20/DRSP/L-5-MTHF Ca for Period 3. YAZ: single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP) / Metafolin: single oral administration of 1 coated SHT04532C tablet, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium [MTHF-Ca]) / 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]).
Treatment Sequence C: EE20/DRSP/L-5-MTHF Ca, YAZ, Metafolin EE20/DRSP/L-5-MTHF Ca for Period 1; YAZ for Period 2; Metafolin for Period 3. 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]) / YAZ: single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP) / Metafolin: single oral administration of 1 coated SHT04532C tablet, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium [MTHF-Ca]).
Treatment Sequence D: EE20/DRSP/L-5-MTHF Ca, Metafolin, YAZ EE20/DRSP/L-5-MTHF Ca for Period 1; Metafolin for Period 2; YAZ for Period 3. 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]) / Metafolin: single oral administration of 1 coated SHT04532C tablet, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium [MTHF-Ca]) / YAZ: single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP).
Treatment Sequence E: Metafolin, YAZ, EE20/DRSP/L-5-MTHF Ca Metafolin for Period 1; YAZ for Period 2; EE20/DRSP/L-5-MTHF Ca for Period 3. Metafolin: single oral administration of 1 coated SHT04532C tablet, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium [MTHF-Ca]) / YAZ: single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP) / 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]).
Treatment Sequence F: Metafolin, EE20/DRSP/L-5-MTHF Ca, YAZ Metafolin for Period 1; EE20/DRSP/L-5-MTHF Ca for Period 2; YAZ for Period 3. Metafolin: single oral administration of 1 coated SHT04532C tablet, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium [MTHF-Ca]) / 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]) / YAZ: single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP).

Participant Flow for 3 periods

Period 1:   Period 1
    Treatment Sequence A: YAZ, EE20/DRSP/L-5-MTHF Ca, Metafolin   Treatment Sequence B: YAZ, Metafolin, EE20/DRSP/L-5-MTHF Ca   Treatment Sequence C: EE20/DRSP/L-5-MTHF Ca, YAZ, Metafolin   Treatment Sequence D: EE20/DRSP/L-5-MTHF Ca, Metafolin, YAZ   Treatment Sequence E: Metafolin, YAZ, EE20/DRSP/L-5-MTHF Ca   Treatment Sequence F: Metafolin, EE20/DRSP/L-5-MTHF Ca, YAZ
STARTED   7   8   7   7   9   6 
COMPLETED   7   8   7   7   9   6 
NOT COMPLETED   0   0   0   0   0   0 

Period 2:   Period 2
    Treatment Sequence A: YAZ, EE20/DRSP/L-5-MTHF Ca, Metafolin   Treatment Sequence B: YAZ, Metafolin, EE20/DRSP/L-5-MTHF Ca   Treatment Sequence C: EE20/DRSP/L-5-MTHF Ca, YAZ, Metafolin   Treatment Sequence D: EE20/DRSP/L-5-MTHF Ca, Metafolin, YAZ   Treatment Sequence E: Metafolin, YAZ, EE20/DRSP/L-5-MTHF Ca   Treatment Sequence F: Metafolin, EE20/DRSP/L-5-MTHF Ca, YAZ
STARTED   7   8   7   7   9   6 
COMPLETED   7   8   7   7   8   6 
NOT COMPLETED   0   0   0   0   1   0 
Withdrawal by Subject                0                0                0                0                1                0 

Period 3:   Period 3
    Treatment Sequence A: YAZ, EE20/DRSP/L-5-MTHF Ca, Metafolin   Treatment Sequence B: YAZ, Metafolin, EE20/DRSP/L-5-MTHF Ca   Treatment Sequence C: EE20/DRSP/L-5-MTHF Ca, YAZ, Metafolin   Treatment Sequence D: EE20/DRSP/L-5-MTHF Ca, Metafolin, YAZ   Treatment Sequence E: Metafolin, YAZ, EE20/DRSP/L-5-MTHF Ca   Treatment Sequence F: Metafolin, EE20/DRSP/L-5-MTHF Ca, YAZ
STARTED   7   8   7   7   8   6 
COMPLETED   6   7   7   7   7   6 
NOT COMPLETED   1   1   0   0   1   0 
Pregnancy                1                0                0                0                0                0 
difficulty with blood sampling                0                1                0                0                0                0 
non-compliance                0                0                0                0                1                0 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Entire Study Population Includes all participants treated

Baseline Measures
   Entire Study Population 
Overall Participants Analyzed 
[Units: Participants]
 44 
Age 
[Units: Years]
Mean (Standard Deviation)
 26.3  (6.33) 
Gender 
[Units: Participants]
 
Female   44 
Male   0 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Mean Maximum Concentration (Cmax) of EE Incl. Bioequivalence (BE) Evaluation   [ Time Frame: up to 96 hours after administration ]

2.  Primary:   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 ]

3.  Primary:   Mean Maximum Concentration (Cmax) of DRSP Incl. Bioequivalence (BE) Evaluation   [ Time Frame: up to 168 hours after administration ]

4.  Primary:   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 ]

5.  Primary:   Mean Maximum Concentration (Cmax) of L-5-methyl-THF (Baseline Corrected) Incl. Bioequivalence (BE) Evaluation   [ Time Frame: up to 12 hours after administration ]

6.  Primary:   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 ]

7.  Primary:   Mean Maximum Concentration (Cmax) of L-5-methyl-THF (Baseline Uncorrected) Incl. Bioequivalence (BE) Evaluation   [ Time Frame: up to 12 hours after administration ]

8.  Primary:   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 ]

9.  Secondary:   Time to Reach Maximum Concentration (Tmax) of EE   [ Time Frame: up to 96 hours after administration ]

10.  Secondary:   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 ]

11.  Secondary:   Time to Reach Maximum Concentration (Tmax) of DRSP   [ Time Frame: up to 168 hours after administration ]

12.  Secondary:   Time to Reach Maximum Concentration (Tmax) of L-5-methyl-THF   [ Time Frame: up to 12 hours after administration ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Therapeutic Area Head
Organization: Bayer HealthCare AG
e-mail: clinical-trials-contact@bayerhealthcare.com


Publications of Results:

Responsible Party: Head Clinical Pharmacology, Bayer Healthcare AG
ClinicalTrials.gov Identifier: NCT01253187     History of Changes
Other Study ID Numbers: 91460
2005-003049-15 ( EudraCT Number )
309664 ( Other Identifier: Company Internal )
First Submitted: December 2, 2010
First Posted: December 3, 2010
Results First Submitted: December 9, 2010
Results First Posted: May 9, 2011
Last Update Posted: August 7, 2013