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Efficacy and Safety Study for an Oral Contraceptive Containing Folate

This study has been completed.
Sponsor:
Information provided by:
Bayer
ClinicalTrials.gov Identifier:
NCT00468481
First received: April 30, 2007
Last updated: October 31, 2012
Last verified: October 2012
History of Changes
Results First Received: January 4, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Prevention
Conditions: Neural Tube Defects
Contraception
Oral Contraceptives (OC)
Interventions: Drug: Drospirenone/Ethinylestradiol/Methyltetrahydrofolate
Drug: Drospirenone/Ethinylestradiol (Yaz)

  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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
572 subjects screened; 187 subjects screen failed; 385 subjects randomized

Reporting Groups
  Description
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) 1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
Drospirenone (DRSP)/Ethinylestradiol (EE) 1 tablet 0.020 mg EE/3.0 mg DRSP [YAZ] given orally/daily for 24 days followed by 1 placebo tablet given orally/daily for 4 days over a time period of 24 weeks

Participant Flow:   Overall Study
    Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)     Drospirenone (DRSP)/Ethinylestradiol (EE)  
STARTED     291 [1]   94  
Subjects Treated     285     94  
COMPLETED     203     70  
NOT COMPLETED     88     24  
Adverse Event                 13                 3  
Lost to Follow-up                 25                 8  
Pregnancy                 2                 0  
Protocol Violation                 18                 8  
Withdrawal by Subject                 12                 3  
susp/diag malignant/premalignant disease                 1                 0  
Prohibited Medication                 1                 1  
Egg Donor                 1                 0  
Moved out of area                 4                 1  
Non-Compliance                 5                 0  
Unknown                 6                 0  
[1] 6 of these randomized subjects did not take any study medication



  Baseline Characteristics
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Reporting Groups
  Description
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) 1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
Drospirenone (DRSP)/Ethinylestradiol (EE) 1 tablet 0.020 mg EE/3.0 mg DRSP [YAZ] given orally/daily for 24 days followed by 1 placebo tablet given orally/daily for 4 days over a time period of 24 weeks
Total Total of all reporting groups

Baseline Measures
    Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)     Drospirenone (DRSP)/Ethinylestradiol (EE)     Total  
Number of Participants  
[units: participants]
 		  285     94     379  
Age  
[units: years]
Mean ( Full Range ) 		  24.8  
  ( 18 to 40 )   		  24.6  
  ( 18 to 39 )   		  24.7  
  ( 18 to 40 )  
Gender  
[units: participants]
 		     
Female     285     94     379  
Male     0     0     0  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Red Blood Cell (RBC) Folate Level at 24 Weeks   [ Time Frame: Week 24 ]
  Show Outcome Measure 1

2.  Primary:   Plasma Folate Level at 24 Weeks   [ Time Frame: Week 24 ]
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3.  Secondary:   Mean Neural Tube Defect (NTD) Risk Reduction at Week 24   [ Time Frame: Baseline and week 24 ]
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4.  Secondary:   Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 4   [ Time Frame: baseline and up to week 4 ]
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5.  Secondary:   Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 8   [ Time Frame: baseline and up to week 8 ]
  Show Outcome Measure 5

6.  Secondary:   Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 12   [ Time Frame: baseline and up to week 12 ]
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7.  Secondary:   Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 16   [ Time Frame: baseline and up to week 16 ]
  Show Outcome Measure 7

8.  Secondary:   Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 20   [ Time Frame: baseline and up to week 20 ]
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9.  Secondary:   Mean Change From Baseline in Plasma Folate Levels at Week 4   [ Time Frame: baseline and up to week 4 ]
  Show Outcome Measure 9

10.  Secondary:   Mean Change From Baseline in Plasma Folate Levels at Week 8   [ Time Frame: baseline and up to week 8 ]
  Show Outcome Measure 10

11.  Secondary:   Mean Change From Baseline in Plasma Folate Levels at Week 12   [ Time Frame: baseline and up to week 12 ]
  Show Outcome Measure 11

12.  Secondary:   Mean Change From Baseline in Plasma Folate Levels at Week 16   [ Time Frame: baseline and up to week 16 ]
  Show Outcome Measure 12

13.  Secondary:   Mean Change From Baseline in Plasma Folate Levels at Week 20   [ Time Frame: baseline and up to week 20 ]
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14.  Secondary:   Mean Change From Baseline in Plasma Homocysteine Levels at Week 4   [ Time Frame: baseline and up to week 4 ]
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15.  Secondary:   Mean Change From Baseline in Plasma Homocysteine Levels at Week 8   [ Time Frame: baseline and up to week 8 ]
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16.  Secondary:   Mean Change From Baseline in Plasma Homocysteine Levels at Week 12   [ Time Frame: baseline and up to week 12 ]
  Show Outcome Measure 16

17.  Secondary:   Mean Change From Baseline in Plasma Homocysteine Levels at Week 16   [ Time Frame: baseline and up to week 16 ]
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18.  Secondary:   Mean Change From Baseline in Plasma Homocysteine Levels at Week 20   [ Time Frame: baseline and up to week 20 ]
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19.  Secondary:   Mean Change From Baseline in Plasma Homocysteine Levels at Week 24   [ Time Frame: baseline and up to week 24 ]
  Show Outcome Measure 19

20.  Post-Hoc:   Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Baseline   [ Time Frame: at baseline (week 0) ]
  Show Outcome Measure 20

21.  Post-Hoc:   Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Baseline   [ Time Frame: at baseline (week 0) ]
  Show Outcome Measure 21

22.  Post-Hoc:   Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 4   [ Time Frame: up to week 4 ]
  Show Outcome Measure 22

23.  Post-Hoc:   Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 4   [ Time Frame: up to week 4 ]
  Show Outcome Measure 23

24.  Post-Hoc:   Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 8   [ Time Frame: up to week 8 ]
  Show Outcome Measure 24

25.  Post-Hoc:   Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 8   [ Time Frame: up to week 8 ]
  Show Outcome Measure 25

26.  Post-Hoc:   Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 12   [ Time Frame: up to week 12 ]
  Show Outcome Measure 26

27.  Post-Hoc:   Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 12   [ Time Frame: up to week 12 ]
  Show Outcome Measure 27

28.  Post-Hoc:   Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 16   [ Time Frame: up to week 16 ]
  Show Outcome Measure 28

29.  Post-Hoc:   Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 16   [ Time Frame: up to week 16 ]
  Show Outcome Measure 29

30.  Post-Hoc:   Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 20   [ Time Frame: up to week 20 ]
  Show Outcome Measure 30

31.  Post-Hoc:   Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 20   [ Time Frame: up to week 20 ]
  Show Outcome Measure 31

32.  Post-Hoc:   Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 24   [ Time Frame: up to week 24 ]
  Show Outcome Measure 32

33.  Post-Hoc:   Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 24   [ Time Frame: up to week 24 ]
  Show Outcome Measure 33

34.  Post-Hoc:   Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Baseline   [ Time Frame: at baseline (week 0) ]
  Show Outcome Measure 34

35.  Post-Hoc:   Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Baseline   [ Time Frame: at baseline (week 0) ]
  Show Outcome Measure 35

36.  Post-Hoc:   Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 4   [ Time Frame: up to week 4 ]
  Show Outcome Measure 36

37.  Post-Hoc:   Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 4   [ Time Frame: up to week 4 ]
  Show Outcome Measure 37

38.  Post-Hoc:   Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 8   [ Time Frame: up to week 8 ]
  Show Outcome Measure 38

39.  Post-Hoc:   Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 8   [ Time Frame: up to week 8 ]
  Show Outcome Measure 39

40.  Post-Hoc:   Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 12   [ Time Frame: up to week 12 ]
  Show Outcome Measure 40

41.  Post-Hoc:   Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 12   [ Time Frame: up to week 12 ]
  Show Outcome Measure 41

42.  Post-Hoc:   Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 16   [ Time Frame: up to week 16 ]
  Show Outcome Measure 42

43.  Post-Hoc:   Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 16   [ Time Frame: up to week 16 ]
  Show Outcome Measure 43

44.  Post-Hoc:   Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 20   [ Time Frame: up to week 20 ]
  Show Outcome Measure 44

45.  Post-Hoc:   Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 20   [ Time Frame: up to week 20 ]
  Show Outcome Measure 45

46.  Post-Hoc:   Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 24   [ Time Frame: up to week 24 ]
  Show Outcome Measure 46

47.  Post-Hoc:   Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 24   [ Time Frame: up to week 24 ]
  Show Outcome Measure 47


  Serious Adverse Events
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  Other Adverse Events
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Time Frame No text entered.
Additional Description No text entered.

Frequency Threshold
Threshold above which other adverse events are reported   2%  

Reporting Groups
  Description
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) 1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
Drospirenone (DRSP)/Ethinylestradiol (EE) 1 tablet 0.020 mg EE/3.0 mg DRSP [YAZ] given orally/daily for 24 days followed by 1 placebo tablet given orally/daily for 4 days over a time period of 24 weeks

Other Adverse Events
    Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)     Drospirenone (DRSP)/Ethinylestradiol (EE)  
Total, other (not including serious) adverse events      
# participants affected / at risk     103/285     44/94  
Gastrointestinal disorders      
Abdominal pain * 1    
# participants affected / at risk     1/285 (0.35%)     3/94 (3.19%)  
# events     1     3  
Infections and infestations      
Bronchitis * 1    
# participants affected / at risk     6/285 (2.11%)     1/94 (1.06%)  
# events     6     1  
Influenza * 1    
# participants affected / at risk     6/285 (2.11%)     3/94 (3.19%)  
# events     6     3  
Nasopharyngitis * 1    
# participants affected / at risk     11/285 (3.86%)     2/94 (2.13%)  
# events     11     2  
Pharyngitis * 1    
# participants affected / at risk     1/285 (0.35%)     2/94 (2.13%)  
# events     1     2  
Sinusitis * 1    
# participants affected / at risk     9/285 (3.16%)     3/94 (3.19%)  
# events     9     3  
Upper respiratory tract infection * 1    
# participants affected / at risk     30/285 (10.53%)     9/94 (9.57%)  
# events     32     10  
Urinary tract infection * 1    
# participants affected / at risk     10/285 (3.51%)     2/94 (2.13%)  
# events     11     2  
Investigations      
Blood cholinesterase decreased * 1    
# participants affected / at risk     1/285 (0.35%)     2/94 (2.13%)  
# events     1     2  
Blood triglycerides increased * 1    
# participants affected / at risk     0/285 (0.00%)     2/94 (2.13%)  
# events     0     2  
Gamma-glutamyltransferase increased * 1    
# participants affected / at risk     2/285 (0.70%)     2/94 (2.13%)  
# events     2     2  
Low density lipoprotein increased * 1    
# participants affected / at risk     17/285 (5.96%)     8/94 (8.51%)  
# events     17     8  
Prothrombin level decreased * 1    
# participants affected / at risk     0/285 (0.00%)     2/94 (2.13%)  
# events     0     2  
Human papilloma virus test positive * 1    
# participants affected / at risk     10/285 (3.51%)     2/94 (2.13%)  
# events     10     2  
Musculoskeletal and connective tissue disorders      
Arthralgia * 1    
# participants affected / at risk     1/285 (0.35%)     2/94 (2.13%)  
# events     1     2  
Nervous system disorders      
Headache * 1    
# participants affected / at risk     6/285 (2.11%)     4/94 (4.26%)  
# events     9     6  
Migraine * 1    
# participants affected / at risk     2/285 (0.70%)     2/94 (2.13%)  
# events     3     2  
Psychiatric disorders      
Anxiety * 1    
# participants affected / at risk     1/285 (0.35%)     3/94 (3.19%)  
# events     1     3  
Reproductive system and breast disorders      
Cervical dysplasia * 1    
# participants affected / at risk     10/285 (3.51%)     4/94 (4.26%)  
# events     10     4  
Respiratory, thoracic and mediastinal disorders      
Cough * 1    
# participants affected / at risk     5/285 (1.75%)     5/94 (5.32%)  
# events     5     5  
Sinus congestion * 1    
# participants affected / at risk     0/285 (0.00%)     2/94 (2.13%)  
# events     0     2  
Oropharyngeal pain * 1    
# participants affected / at risk     0/285 (0.00%)     2/94 (2.13%)  
# events     0     2  
Skin and subcutaneous tissue disorders      
Rash * 1    
# participants affected / at risk     5/285 (1.75%)     5/94 (5.32%)  
# events     5     5  
* Events were collected by non-systematic assessment
1 Term from vocabulary, MedDRA 11.1



  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 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.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Limitations and Caveats
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.  


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


Publications of Results:


Responsible Party: Therapeutic Area Head, Bayer Healthcare Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00468481     History of Changes
Other Study ID Numbers: 91523, 310662
Study First Received: April 30, 2007
Results First Received: January 4, 2011
Last Updated: October 31, 2012
Health Authority: United States: Food and Drug Administration