Efficacy and Safety Study for an Oral Contraceptive Containing Folate

• Sponsor: Bayer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00468481
• Collaborator: (none)
• Enrollment: 385
• Locations: 9
• Arms: 2
• Duration (Months): 17.1
• Patients Per Site: 42.8
• Patients Per Site Per Month: 2.5

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether the study drug is safe and effective

Condition or Disease	Intervention/Treatment	Phase
Neural Tube Defects; Contraception; Oral Contraceptives (OC)	Drug: Drospirenone/Ethinylestradiol/Methyltetrahydrofolate; Drug: Drospirenone/Ethinylestradiol (Yaz)	Phase 3

Detailed Description

Acronym is used in result section: suspected/diagnosed (susp/diag)

Study Design

• Study Type: Interventional
• Actual Enrollment: 385 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: Multi-Center, Randomized, Double-Blind Active-Controlled, Parallel Group Study to Investigate Plasma Folate, Red Blood Cell Folate and Homocysteine Levels During a 24 Week Oral Administration of an OC Containing Folate Compared to OC Alone
• Study Start Date: Apr 1, 2007
• Actual Primary Completion Date: Aug 1, 2008
• Actual Study Completion Date: Sep 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Drug: Drospirenone/Ethinylestradiol/Methyltetrahydrofolate; 0.020 mg ethinylestradiol with 3.0 mg drospirenone and 0.451 mg L-5-methyltetrahydrofolate (L-5-MTHF)
Active Comparator: 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	Drug: Drospirenone/Ethinylestradiol (Yaz); 0.020 mg ethinylestradiol with 3.0 mg drospirenone

Outcome Measures

Primary Outcome Measures

1. Red Blood Cell (RBC) Folate Level at 24 Weeks [Week 24]

   RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit

2. Plasma Folate Level at 24 Weeks [Week 24]

   Folate concentrations in plasma were determined by an appropriately validated microbiological assay.

Secondary Outcome Measures

1. Mean Neural Tube Defect (NTD) Risk Reduction at Week 24 [Baseline and week 24]

   The mean NTD risk reduction evaluated as the change from Baseline to Week 24 in NTD risk based on the formula of Daly et al (J Amer Med Assoc 1995;274(21):1698-702); NTD risk=exp (1.6463-1.2193 x natural log [RBC folate]) where natural log [RBC folate] is the natural log of RBC folate measured in nmol/L; Change from Baseline to Week 24 in NTD risk=NTD risk at Week 24 - NTD risk at Baseline

2. Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 4 [baseline and up to week 4]

   RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit

3. Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 8 [baseline and up to week 8]

   RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit

4. Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 12 [baseline and up to week 12]

   RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit

5. Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 16 [baseline and up to week 16]

   RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit

6. Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 20 [baseline and up to week 20]

   RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit

7. Mean Change From Baseline in Plasma Folate Levels at Week 4 [baseline and up to week 4]

   Folate concentrations in plasma were determined by an appropriately validated microbiological assay.

8. Mean Change From Baseline in Plasma Folate Levels at Week 8 [baseline and up to week 8]

   Folate concentrations in plasma were determined by an appropriately validated microbiological assay.

9. Mean Change From Baseline in Plasma Folate Levels at Week 12 [baseline and up to week 12]

   Folate concentrations in plasma were determined by an appropriately validated microbiological assay.

10. Mean Change From Baseline in Plasma Folate Levels at Week 16 [baseline and up to week 16]

    Folate concentrations in plasma were determined by an appropriately validated microbiological assay.

11. Mean Change From Baseline in Plasma Folate Levels at Week 20 [baseline and up to week 20]

    Folate concentrations in plasma were determined by an appropriately validated microbiological assay.

12. Mean Change From Baseline in Plasma Homocysteine Levels at Week 4 [baseline and up to week 4]

    Homocysteine concentrations in plasma were determined by Fluorescence Polarization Immunoassays (FPIA) using the Abbot AxSym analyzer in a clinical laboratory setting.

13. Mean Change From Baseline in Plasma Homocysteine Levels at Week 8 [baseline and up to week 8]

    Homocysteine concentrations in plasma were determined by Fluorescence Polarization Immunoassays (FPIA) using the Abbot AxSym analyzer in a clinical laboratory setting.

14. Mean Change From Baseline in Plasma Homocysteine Levels at Week 12 [baseline and up to week 12]

    Homocysteine concentrations in plasma were determined by Fluorescence Polarization Immunoassays (FPIA) using the Abbot AxSym analyzer in a clinical laboratory setting.

15. Mean Change From Baseline in Plasma Homocysteine Levels at Week 16 [baseline and up to week 16]

    Homocysteine concentrations in plasma were determined by Fluorescence Polarization Immunoassays (FPIA) using the Abbot AxSym analyzer in a clinical laboratory setting.

16. Mean Change From Baseline in Plasma Homocysteine Levels at Week 20 [baseline and up to week 20]

    Homocysteine concentrations in plasma were determined by Fluorescence Polarization Immunoassays (FPIA) using the Abbot AxSym analyzer in a clinical laboratory setting.

17. Mean Change From Baseline in Plasma Homocysteine Levels at Week 24 [baseline and up to week 24]

    Homocysteine concentrations in plasma were determined by Fluorescence Polarization Immunoassays (FPIA) using the Abbot AxSym analyzer in a clinical laboratory setting.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 40 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy women between 18 and 40 requesting oral contraception

Exclusion Criteria:

• The use of steroidal oral contraceptives, or any drug that could alter Oral Contraception metabolism will be prohibited during the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Orange County Clinical Trials	Anaheim	California	United States	92801
2	Medical Center for Clinical Research	San Diego	California	United States	92108
3	SNBL Clinical Pharmacology Center, Inc.	Baltimore	Maryland	United States	21201
4	Columbia University Medical Center	New York	New York	United States	10032
5	AAIPharma, Inc.	Morrisville	North Carolina	United States	27560
6	Lyndhurst Gynecologic Associates	Winston-Salem	North Carolina	United States	27103
7	Coastal Carolina Research Center	Mt. Pleasant	South Carolina	United States	29464
8	New Orleans Center for Clinical Research	Knoxville	Tennessee	United States	37920
9	NorthWest Kinetics	Tacoma	Washington	United States	98418

Sponsors and Collaborators

• Bayer

Investigators

• Study Director: Bayer Study Director, Bayer

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT00468481
• Other Study ID Numbers: 91523; 310662
• First Posted: May 2, 2007
• Last Update Posted: Apr 23, 2014
• Last Verified: Apr 1, 2014

• Keywords provided by Bayer: Healthy women requesting contraception; Folic Acid
• Additional relevant MeSH terms: Neural Tube Defects; Spinal Dysraphism; Drospirenone; Ethinyl Estradiol; Drospirenone and ethinyl estradiol combination

Study Results

Participant Flow

Pre-assignment Detail	572 subjects screened; 187 subjects screen failed; 385 subjects randomized

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Period Title: Overall Study
STARTED	291	94
Subjects Treated	285	94
COMPLETED	203	70
NOT COMPLETED	88	24

Baseline Characteristics

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)	Total
Arm/Group Description	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	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 of all reporting groups
Overall Participants	285	94	379
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	24.8	24.6	24.7
Sex: Female, Male (Count of Participants)
Female	285 100%	94 100%	379 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Red Blood Cell (RBC) Folate Level at 24 Weeks
Description	RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	124	45
Least Squares Mean (95% Confidence Interval) [nmol/L]	1406.91	1022.21

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF), Drospirenone (DRSP)/Ethinylestradiol (EE)
	Comments	The null hypothesis was that the difference between DRSP/EE/MTHF and Yaz treatment groups in the RBC folate levels at week 24 was 0.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	Analysis of Covariance (ANCOVA) with treatment as factor and Baseline (RBC folate) as covariate
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	384.70
	Confidence Interval	() 95%; 282.42 to 486.98
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference = DRSP/EE/MTHF - YAZ

2. Primary Outcome

Title	Plasma Folate Level at 24 Weeks
Description	Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	196	66
Least Squares Mean (95% Confidence Interval) [nmol/L]	60.55	41.67

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF), Drospirenone (DRSP)/Ethinylestradiol (EE)
	Comments	The null hypothesis was that the difference between DRSP/EE/MTHF and Yaz treatment groups in the plasma folate levels at week 24 was 0.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	Analysis of Covariance (ANCOVA) with treatment as factor and Baseline (plasma folate) as covariate
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	18.87
	Confidence Interval	() 95%; 14.04 to 23.70
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference =DRSP/EE/MTHF - YAZ

3. Secondary Outcome

Title	Mean Neural Tube Defect (NTD) Risk Reduction at Week 24
Description	The mean NTD risk reduction evaluated as the change from Baseline to Week 24 in NTD risk based on the formula of Daly et al (J Amer Med Assoc 1995;274(21):1698-702); NTD risk=exp (1.6463-1.2193 x natural log [RBC folate]) where natural log [RBC folate] is the natural log of RBC folate measured in nmol/L; Change from Baseline to Week 24 in NTD risk=NTD risk at Week 24 - NTD risk at Baseline
Time Frame	Baseline and week 24

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	124	45
Mean (Standard Deviation) [per 1000 birth]	-0.51 (0.41)	-0.03 (0.26)

4. Secondary Outcome

Title	Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 4
Description	RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit
Time Frame	baseline and up to week 4

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	125	43
Mean (Standard Deviation) [nmol/L]	110.9 (207.28)	-37.6 (195.88)

5. Secondary Outcome

Title	Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 8
Description	RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit
Time Frame	baseline and up to week 8

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	122	43
Mean (Standard Deviation) [nmol/L]	310.3 (231.47)	68.2 (155.26)

6. Secondary Outcome

Title	Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 12
Description	RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit
Time Frame	baseline and up to week 12

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	127	41
Mean (Standard Deviation) [nmol/L]	405.8 (243.88)	86.5 (177.81)

7. Secondary Outcome

Title	Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 16
Description	RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit
Time Frame	baseline and up to week 16

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	120	46
Mean (Standard Deviation) [nmol/L]	448.9 (280.37)	68.0 (186.44)

8. Secondary Outcome

Title	Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 20
Description	RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit
Time Frame	baseline and up to week 20

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	123	44
Mean (Standard Deviation) [nmol/L]	452.7 (284.64)	64.6 (194.89)

9. Secondary Outcome

Title	Mean Change From Baseline in Plasma Folate Levels at Week 4
Description	Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time Frame	baseline and up to week 4

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	192	65
Mean (Standard Deviation) [nmol/L]	15.2 (22.07)	0.6 (14.29)

10. Secondary Outcome

Title	Mean Change From Baseline in Plasma Folate Levels at Week 8
Description	Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time Frame	baseline and up to week 8

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	193	66
Mean (Standard Deviation) [µg/L]	18.4 (19.17)	2.2 (14.63)

11. Secondary Outcome

Title	Mean Change From Baseline in Plasma Folate Levels at Week 12
Description	Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time Frame	baseline and up to week 12

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	194	66
Mean (Standard Deviation) [nmol/L]	17.6 (20.1)	0.3 (15.24)

12. Secondary Outcome

Title	Mean Change From Baseline in Plasma Folate Levels at Week 16
Description	Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time Frame	baseline and up to week 16

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	194	65
Mean (Standard Deviation) [nmol/L]	17.6 (12.43)	2.4 (16.44)

13. Secondary Outcome

Title	Mean Change From Baseline in Plasma Folate Levels at Week 20
Description	Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time Frame	baseline and up to week 20

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	193	66
Mean (Standard Deviation) [nmol/L]	15.1 (22.71)	-1.6 (15.65)

14. Secondary Outcome

Title	Mean Change From Baseline in Plasma Homocysteine Levels at Week 4
Description	Homocysteine concentrations in plasma were determined by Fluorescence Polarization Immunoassays (FPIA) using the Abbot AxSym analyzer in a clinical laboratory setting.
Time Frame	baseline and up to week 4

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	194	65
Mean (Standard Deviation) [µg/L]	0 (1.04)	0 (0.69)

15. Secondary Outcome

Title	Mean Change From Baseline in Plasma Homocysteine Levels at Week 8
Description	Homocysteine concentrations in plasma were determined by Fluorescence Polarization Immunoassays (FPIA) using the Abbot AxSym analyzer in a clinical laboratory setting.
Time Frame	baseline and up to week 8

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	195	66
Mean (Standard Deviation) [µg/L]	-0.2 (0.9)	0 (1)

16. Secondary Outcome

Title	Mean Change From Baseline in Plasma Homocysteine Levels at Week 12
Description	Homocysteine concentrations in plasma were determined by Fluorescence Polarization Immunoassays (FPIA) using the Abbot AxSym analyzer in a clinical laboratory setting.
Time Frame	baseline and up to week 12

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	196	66
Mean (Standard Deviation) [µg/L]	-0.3 (1.07)	0 (0.93)

17. Secondary Outcome

Title	Mean Change From Baseline in Plasma Homocysteine Levels at Week 16
Description	Homocysteine concentrations in plasma were determined by Fluorescence Polarization Immunoassays (FPIA) using the Abbot AxSym analyzer in a clinical laboratory setting.
Time Frame	baseline and up to week 16

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	194	65
Mean (Standard Deviation) [µg/L]	-0.2 (1.02)	-0.1 (0.93)

18. Secondary Outcome

Title	Mean Change From Baseline in Plasma Homocysteine Levels at Week 20
Description	Homocysteine concentrations in plasma were determined by Fluorescence Polarization Immunoassays (FPIA) using the Abbot AxSym analyzer in a clinical laboratory setting.
Time Frame	baseline and up to week 20

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	195	66
Mean (Standard Deviation) [µg/L]	-0.2 (1.07)	-0.2 (0.91)

19. Secondary Outcome

Title	Mean Change From Baseline in Plasma Homocysteine Levels at Week 24
Description	Homocysteine concentrations in plasma were determined by Fluorescence Polarization Immunoassays (FPIA) using the Abbot AxSym analyzer in a clinical laboratory setting.
Time Frame	baseline and up to week 24

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	195	66
Mean (Standard Deviation) [µg/L]	-0.3 (0.93)	0.1 (1.24)

20. Post-Hoc Outcome

Title	Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Baseline
Description	RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit
Time Frame	at baseline (week 0)

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	90	40
Mean (Standard Deviation) [nmol/L]	910.9 (276.05)	915.1 (233.97)

21. Post-Hoc Outcome

Title	Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Baseline
Description	RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit
Time Frame	at baseline (week 0)

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	54	12
Mean (Standard Deviation) [nmol/L]	1122.8 (504.7)	1345.0 (301.76)

22. Post-Hoc Outcome

Title	Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 4
Description	RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit
Time Frame	up to week 4

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	80	35
Mean (Standard Deviation) [nmol/L]	1007.1 (329.67)	889.5 (262.42)

23. Post-Hoc Outcome

Title	Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 4
Description	RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit
Time Frame	up to week 4

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	50	9
Mean (Standard Deviation) [nmol/L]	1175.7 (428.58)	1256.1 (190.89)

24. Post-Hoc Outcome

Title	Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 8
Description	RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit
Time Frame	up to week 8

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	76	33
Mean (Standard Deviation) [nmol/L]	1184.8 (338.5)	970.4 (252.79)

25. Post-Hoc Outcome

Title	Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 8
Description	RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit
Time Frame	up to week 8

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	50	10
Mean (Standard Deviation) [nmol/L]	1412.7 (436.69)	1407.6 (290.18)

26. Post-Hoc Outcome

Title	Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 12
Description	RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit
Time Frame	up to week 12

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	79	33
Mean (Standard Deviation) [nmol/L]	1308.9 (374.61)	1025.2 (287.55)

27. Post-Hoc Outcome

Title	Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 12
Description	RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit
Time Frame	up to week 12

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	50	10
Mean (Standard Deviation) [nmol/L]	1469.8 (454.62)	1378.4 (375.15)

28. Post-Hoc Outcome

Title	Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 16
Description	RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit
Time Frame	up to week 16

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	76	35
Mean (Standard Deviation) [nmol/L]	1365.2 (403.12)	967.6 (255.78)

29. Post-Hoc Outcome

Title	Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 16
Description	RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit
Time Frame	up to week 16

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	50	11
Mean (Standard Deviation) [nmol/L]	1460.5 (472.23)	1454.7 (355.5)

30. Post-Hoc Outcome

Title	Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 20
Description	RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit
Time Frame	up to week 20

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	78	33
Mean (Standard Deviation) [nmol/L]	1419.8 (558.1)	981.3 (252.85)

31. Post-Hoc Outcome

Title	Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 20
Description	RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit
Time Frame	up to week 20

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	49	13
Mean (Standard Deviation) [nmol/L]	1486.6 (462.8)	1435.9 (319.33)

32. Post-Hoc Outcome

Title	Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 24
Description	RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit
Time Frame	up to week 24

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	87	37
Mean (Standard Deviation) [nmol/L]	1355.3 (364.85)	949.2 (256.26)

33. Post-Hoc Outcome

Title	Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 24
Description	RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit
Time Frame	up to week 24

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	51	10
Mean (Standard Deviation) [nmol/L]	1500.3 (525.71)	1316.1 (237.44)

34. Post-Hoc Outcome

Title	Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Baseline
Description	Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time Frame	at baseline (week 0)

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	120	47
Mean (Standard Deviation) [nmol/L]	41.7 (16.2)	41.5 (15.57)

35. Post-Hoc Outcome

Title	Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Baseline
Description	Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time Frame	at baseline (week 0)

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	76	19
Mean (Standard Deviation) [nmol/L]	50.3 (18.45)	47.1 (17.3)

36. Post-Hoc Outcome

Title	Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 4
Description	Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time Frame	up to week 4

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	119	47
Mean (Standard Deviation) [nmol/L]	59.6 (24.83)	43.1 (17.98)

37. Post-Hoc Outcome

Title	Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 4
Description	Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time Frame	up to week 4

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	73	18
Mean (Standard Deviation) [nmol/L]	60.4 (27.56)	45.9 (21.19)

38. Post-Hoc Outcome

Title	Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 8
Description	Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time Frame	up to week 8

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	118	47
Mean (Standard Deviation) [nmol/L]	60.8 (22.41)	41.8 (14.96)

39. Post-Hoc Outcome

Title	Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 8
Description	Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time Frame	up to week 8

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	75	19
Mean (Standard Deviation) [nmol/L]	68.1 (26.60)	54.1 (30.16)

40. Post-Hoc Outcome

Title	Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 12
Description	Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time Frame	up to week 12

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	119	47
Mean (Standard Deviation) [nmol/L]	59.5 (20.39)	42.3 (17.19)

41. Post-Hoc Outcome

Title	Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 12
Description	Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time Frame	up to week 12

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	75	19
Mean (Standard Deviation) [nmol/L]	67.4 (23.69)	46.4 (17.55)

42. Post-Hoc Outcome

Title	Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 16
Description	Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time Frame	up to week 16

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	118	46
Mean (Standard Deviation) [nmol/L]	59.4 (18.89)	43.2 (18.4)

43. Post-Hoc Outcome

Title	Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 16
Description	Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time Frame	up to week 16

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	76	19
Mean (Standard Deviation) [nmol/L]	67.5 (26.38)	51.8 (21.08)

44. Post-Hoc Outcome

Title	Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 20
Description	Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time Frame	up to week 20

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	118	47
Mean (Standard Deviation) [nmol/L]	59.8 (21.11)	39.7 (16.74)

45. Post-Hoc Outcome

Title	Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 20
Description	Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time Frame	up to week 20

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	75	19
Mean (Standard Deviation) [nmol/L]	61.5 (24.16)	45.9 (14.54)

46. Post-Hoc Outcome

Title	Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 24
Description	Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time Frame	up to week 24

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	120	47
Mean (Standard Deviation) [nmol/L]	58.7 (17.73)	39.8 (18.02)

47. Post-Hoc Outcome

Title	Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 24
Description	Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time Frame	up to week 24

Outcome Measure Data

Analysis Population Description

Analysis was based on Per Protocol Set (PPS) defined as all subjects who had no major protocol deviations and completed 24 weeks of treatment with valid data for one of the co-primary efficacy variables at baseline and week 24.

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)	Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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	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
Measure Participants	76	19
Mean (Standard Deviation) [nmol/L]	64.0 (22.61)	43.7 (16.5)

Adverse Events

Arm/Group Title	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)		Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm/Group Description	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		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
All Cause Mortality
	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)		Drospirenone (DRSP)/Ethinylestradiol (EE)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)		Drospirenone (DRSP)/Ethinylestradiol (EE)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/285 (1.1%)		0/94 (0%)
Infections and infestations
Pneumonia	1/285 (0.4%)	1	0/94 (0%)	0
Investigations
Human papilloma virus test positive	1/285 (0.4%)	1	0/94 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cervix carcinoma stage 0	1/285 (0.4%)	1	0/94 (0%)	0
Reproductive system and breast disorders
Cervical dysplasia	1/285 (0.4%)	1	0/94 (0%)	0
Other (Not Including Serious) Adverse Events
	Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)		Drospirenone (DRSP)/Ethinylestradiol (EE)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	103/285 (36.1%)		44/94 (46.8%)
Gastrointestinal disorders
Abdominal pain	1/285 (0.4%)	1	3/94 (3.2%)	3
Infections and infestations
Bronchitis	6/285 (2.1%)	6	1/94 (1.1%)	1
Influenza	6/285 (2.1%)	6	3/94 (3.2%)	3
Nasopharyngitis	11/285 (3.9%)	11	2/94 (2.1%)	2
Pharyngitis	1/285 (0.4%)	1	2/94 (2.1%)	2
Sinusitis	9/285 (3.2%)	9	3/94 (3.2%)	3
Upper respiratory tract infection	30/285 (10.5%)	32	9/94 (9.6%)	10
Urinary tract infection	10/285 (3.5%)	11	2/94 (2.1%)	2
Investigations
Blood cholinesterase decreased	1/285 (0.4%)	1	2/94 (2.1%)	2
Blood triglycerides increased	0/285 (0%)	0	2/94 (2.1%)	2
Gamma-glutamyltransferase increased	2/285 (0.7%)	2	2/94 (2.1%)	2
Low density lipoprotein increased	17/285 (6%)	17	8/94 (8.5%)	8
Prothrombin level decreased	0/285 (0%)	0	2/94 (2.1%)	2
Human papilloma virus test positive	10/285 (3.5%)	10	2/94 (2.1%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	1/285 (0.4%)	1	2/94 (2.1%)	2
Nervous system disorders
Headache	6/285 (2.1%)	9	4/94 (4.3%)	6
Migraine	2/285 (0.7%)	3	2/94 (2.1%)	2
Psychiatric disorders
Anxiety	1/285 (0.4%)	1	3/94 (3.2%)	3
Reproductive system and breast disorders
Cervical dysplasia	10/285 (3.5%)	10	4/94 (4.3%)	4
Respiratory, thoracic and mediastinal disorders
Cough	5/285 (1.8%)	5	5/94 (5.3%)	5
Sinus congestion	0/285 (0%)	0	2/94 (2.1%)	2
Oropharyngeal pain	0/285 (0%)	0	2/94 (2.1%)	2
Skin and subcutaneous tissue disorders
Rash	5/285 (1.8%)	5	5/94 (5.3%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.