Contraception, Neural Tube Defects, Oral Contraceptives (OC)
Conditions
Keywords
Healthy women requesting contraception, Folic Acid
Brief summary
The purpose of this study is to determine whether the study drug is safe and effective
Detailed description
Acronym is used in result section: suspected/diagnosed (susp/diag)
Interventions
DRUGDrospirenone/Ethinylestradiol/Methyltetrahydrofolate
0.020 mg ethinylestradiol with 3.0 mg drospirenone and 0.451 mg L-5-methyltetrahydrofolate (L-5-MTHF)
DRUGDrospirenone/Ethinylestradiol (Yaz)
0.020 mg ethinylestradiol with 3.0 mg drospirenone
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Red Blood Cell (RBC) Folate Level at 24 Weeks | Week 24 | RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit |
| Plasma Folate Level at 24 Weeks | Week 24 | Folate concentrations in plasma were determined by an appropriately validated microbiological assay. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| 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. |
| 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. |
| 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. |
| 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 |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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 |
Countries
United States
Participant flow
Pre-assignment details
572 subjects screened; 187 subjects screen failed; 385 subjects randomized
Participants by arm
| Arm | Count |
|---|---|
| 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 | 285 |
| 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 | 94 |
| Total | 379 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 13 | 3 |
| Overall Study | Egg Donor | 1 | 0 |
| Overall Study | Lost to Follow-up | 25 | 8 |
| Overall Study | Moved out of area | 4 | 1 |
| Overall Study | Non-Compliance | 5 | 0 |
| Overall Study | Other | 6 | 0 |
| Overall Study | Pregnancy | 2 | 0 |
| Overall Study | Prohibited Medication | 1 | 1 |
| Overall Study | Protocol Violation | 18 | 8 |
| Overall Study | susp/diag malignant/premalignant disease | 1 | 0 |
| Overall Study | Withdrawal by Subject | 12 | 3 |
Baseline characteristics
| Characteristic | Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Drospirenone (DRSP)/Ethinylestradiol (EE) | Total |
|---|---|---|---|
| Age, Continuous | 24.8 years | 24.6 years | 24.7 years |
| Sex: Female, Male Female | 285 Participants | 94 Participants | 379 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 103 / 285 | 44 / 94 |
| serious Total, serious adverse events | 3 / 285 | 0 / 94 |
Outcome results
Primary
Plasma Folate Level at 24 Weeks
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time frame: Week 24
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Plasma Folate Level at 24 Weeks | 60.55 nmol/L |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Plasma Folate Level at 24 Weeks | 41.67 nmol/L |
Comparison: 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.p-value: <0.000195% CI: [14.04, 23.7]ANCOVA
Primary
Red Blood Cell (RBC) Folate Level at 24 Weeks
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Time frame: Week 24
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Red Blood Cell (RBC) Folate Level at 24 Weeks | 1406.91 nmol/L |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Red Blood Cell (RBC) Folate Level at 24 Weeks | 1022.21 nmol/L |
Comparison: 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.p-value: <0.000195% CI: [282.42, 486.98]ANCOVA
Secondary
Mean Change From Baseline in Plasma Folate Levels at Week 12
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time frame: baseline and up to week 12
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Change From Baseline in Plasma Folate Levels at Week 12 | 17.6 nmol/L | Standard Deviation 20.1 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Change From Baseline in Plasma Folate Levels at Week 12 | 0.3 nmol/L | Standard Deviation 15.24 |
Secondary
Mean Change From Baseline in Plasma Folate Levels at Week 16
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time frame: baseline and up to week 16
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Change From Baseline in Plasma Folate Levels at Week 16 | 17.6 nmol/L | Standard Deviation 12.43 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Change From Baseline in Plasma Folate Levels at Week 16 | 2.4 nmol/L | Standard Deviation 16.44 |
Secondary
Mean Change From Baseline in Plasma Folate Levels at Week 20
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time frame: baseline and up to week 20
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Change From Baseline in Plasma Folate Levels at Week 20 | 15.1 nmol/L | Standard Deviation 22.71 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Change From Baseline in Plasma Folate Levels at Week 20 | -1.6 nmol/L | Standard Deviation 15.65 |
Secondary
Mean Change From Baseline in Plasma Folate Levels at Week 4
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time frame: baseline and up to week 4
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Change From Baseline in Plasma Folate Levels at Week 4 | 15.2 nmol/L | Standard Deviation 22.07 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Change From Baseline in Plasma Folate Levels at Week 4 | 0.6 nmol/L | Standard Deviation 14.29 |
Secondary
Mean Change From Baseline in Plasma Folate Levels at Week 8
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time frame: baseline and up to week 8
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Change From Baseline in Plasma Folate Levels at Week 8 | 18.4 µg/L | Standard Deviation 19.17 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Change From Baseline in Plasma Folate Levels at Week 8 | 2.2 µg/L | Standard Deviation 14.63 |
Secondary
Mean Change From Baseline in Plasma Homocysteine Levels at Week 12
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Change From Baseline in Plasma Homocysteine Levels at Week 12 | -0.3 µg/L | Standard Deviation 1.07 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Change From Baseline in Plasma Homocysteine Levels at Week 12 | 0 µg/L | Standard Deviation 0.93 |
Secondary
Mean Change From Baseline in Plasma Homocysteine Levels at Week 16
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Change From Baseline in Plasma Homocysteine Levels at Week 16 | -0.2 µg/L | Standard Deviation 1.02 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Change From Baseline in Plasma Homocysteine Levels at Week 16 | -0.1 µg/L | Standard Deviation 0.93 |
Secondary
Mean Change From Baseline in Plasma Homocysteine Levels at Week 20
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Change From Baseline in Plasma Homocysteine Levels at Week 20 | -0.2 µg/L | Standard Deviation 1.07 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Change From Baseline in Plasma Homocysteine Levels at Week 20 | -0.2 µg/L | Standard Deviation 0.91 |
Secondary
Mean Change From Baseline in Plasma Homocysteine Levels at Week 24
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Change From Baseline in Plasma Homocysteine Levels at Week 24 | -0.3 µg/L | Standard Deviation 0.93 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Change From Baseline in Plasma Homocysteine Levels at Week 24 | 0.1 µg/L | Standard Deviation 1.24 |
Secondary
Mean Change From Baseline in Plasma Homocysteine Levels at Week 4
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Change From Baseline in Plasma Homocysteine Levels at Week 4 | 0 µg/L | Standard Deviation 1.04 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Change From Baseline in Plasma Homocysteine Levels at Week 4 | 0 µg/L | Standard Deviation 0.69 |
Secondary
Mean Change From Baseline in Plasma Homocysteine Levels at Week 8
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Change From Baseline in Plasma Homocysteine Levels at Week 8 | -0.2 µg/L | Standard Deviation 0.9 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Change From Baseline in Plasma Homocysteine Levels at Week 8 | 0 µg/L | Standard Deviation 1 |
Secondary
Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 12
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Time frame: baseline and up to week 12
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 12 | 405.8 nmol/L | Standard Deviation 243.88 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 12 | 86.5 nmol/L | Standard Deviation 177.81 |
Secondary
Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 16
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Time frame: baseline and up to week 16
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 16 | 448.9 nmol/L | Standard Deviation 280.37 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 16 | 68.0 nmol/L | Standard Deviation 186.44 |
Secondary
Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 20
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Time frame: baseline and up to week 20
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 20 | 452.7 nmol/L | Standard Deviation 284.64 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 20 | 64.6 nmol/L | Standard Deviation 194.89 |
Secondary
Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 4
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Time frame: baseline and up to week 4
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 4 | 110.9 nmol/L | Standard Deviation 207.28 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 4 | -37.6 nmol/L | Standard Deviation 195.88 |
Secondary
Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 8
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Time frame: baseline and up to week 8
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 8 | 310.3 nmol/L | Standard Deviation 231.47 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 8 | 68.2 nmol/L | Standard Deviation 155.26 |
Secondary
Mean Neural Tube Defect (NTD) Risk Reduction at 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
Time frame: Baseline and week 24
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Neural Tube Defect (NTD) Risk Reduction at Week 24 | -0.51 per 1000 birth | Standard Deviation 0.41 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Neural Tube Defect (NTD) Risk Reduction at Week 24 | -0.03 per 1000 birth | Standard Deviation 0.26 |
Post Hoc
Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Baseline
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time frame: at baseline (week 0)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Baseline | 50.3 nmol/L | Standard Deviation 18.45 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Baseline | 47.1 nmol/L | Standard Deviation 17.3 |
Post Hoc
Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 12
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time frame: up to week 12
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 12 | 67.4 nmol/L | Standard Deviation 23.69 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 12 | 46.4 nmol/L | Standard Deviation 17.55 |
Post Hoc
Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 16
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time frame: up to week 16
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 16 | 67.5 nmol/L | Standard Deviation 26.38 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 16 | 51.8 nmol/L | Standard Deviation 21.08 |
Post Hoc
Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 20
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time frame: up to week 20
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 20 | 61.5 nmol/L | Standard Deviation 24.16 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 20 | 45.9 nmol/L | Standard Deviation 14.54 |
Post Hoc
Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 24
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time frame: up to week 24
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 24 | 64.0 nmol/L | Standard Deviation 22.61 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 24 | 43.7 nmol/L | Standard Deviation 16.5 |
Post Hoc
Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 4
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time frame: up to week 4
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 4 | 60.4 nmol/L | Standard Deviation 27.56 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 4 | 45.9 nmol/L | Standard Deviation 21.19 |
Post Hoc
Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 8
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time frame: up to week 8
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 8 | 68.1 nmol/L | Standard Deviation 26.6 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 8 | 54.1 nmol/L | Standard Deviation 30.16 |
Post Hoc
Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Baseline
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time frame: at baseline (week 0)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Baseline | 41.7 nmol/L | Standard Deviation 16.2 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Baseline | 41.5 nmol/L | Standard Deviation 15.57 |
Post Hoc
Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 12
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time frame: up to week 12
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 12 | 59.5 nmol/L | Standard Deviation 20.39 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 12 | 42.3 nmol/L | Standard Deviation 17.19 |
Post Hoc
Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 16
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time frame: up to week 16
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 16 | 59.4 nmol/L | Standard Deviation 18.89 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 16 | 43.2 nmol/L | Standard Deviation 18.4 |
Post Hoc
Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 20
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time frame: up to week 20
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 20 | 59.8 nmol/L | Standard Deviation 21.11 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 20 | 39.7 nmol/L | Standard Deviation 16.74 |
Post Hoc
Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 24
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time frame: up to week 24
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 24 | 58.7 nmol/L | Standard Deviation 17.73 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 24 | 39.8 nmol/L | Standard Deviation 18.02 |
Post Hoc
Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 4
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time frame: up to week 4
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 4 | 59.6 nmol/L | Standard Deviation 24.83 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 4 | 43.1 nmol/L | Standard Deviation 17.98 |
Post Hoc
Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 8
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time frame: up to week 8
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 8 | 60.8 nmol/L | Standard Deviation 22.41 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 8 | 41.8 nmol/L | Standard Deviation 14.96 |
Post Hoc
Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Baseline
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Time frame: at baseline (week 0)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Baseline | 1122.8 nmol/L | Standard Deviation 504.7 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Baseline | 1345.0 nmol/L | Standard Deviation 301.76 |
Post Hoc
Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 12
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Time frame: up to week 12
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 12 | 1469.8 nmol/L | Standard Deviation 454.62 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 12 | 1378.4 nmol/L | Standard Deviation 375.15 |
Post Hoc
Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 16
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Time frame: up to week 16
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 16 | 1460.5 nmol/L | Standard Deviation 472.23 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 16 | 1454.7 nmol/L | Standard Deviation 355.5 |
Post Hoc
Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 20
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Time frame: up to week 20
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 20 | 1486.6 nmol/L | Standard Deviation 462.8 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 20 | 1435.9 nmol/L | Standard Deviation 319.33 |
Post Hoc
Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 24
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Time frame: up to week 24
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 24 | 1500.3 nmol/L | Standard Deviation 525.71 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 24 | 1316.1 nmol/L | Standard Deviation 237.44 |
Post Hoc
Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 4
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Time frame: up to week 4
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 4 | 1175.7 nmol/L | Standard Deviation 428.58 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 4 | 1256.1 nmol/L | Standard Deviation 190.89 |
Post Hoc
Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 8
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Time frame: up to week 8
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 8 | 1412.7 nmol/L | Standard Deviation 436.69 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 8 | 1407.6 nmol/L | Standard Deviation 290.18 |
Post Hoc
Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Baseline
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Time frame: at baseline (week 0)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Baseline | 910.9 nmol/L | Standard Deviation 276.05 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Baseline | 915.1 nmol/L | Standard Deviation 233.97 |
Post Hoc
Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 12
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Time frame: up to week 12
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 12 | 1308.9 nmol/L | Standard Deviation 374.61 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 12 | 1025.2 nmol/L | Standard Deviation 287.55 |
Post Hoc
Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 16
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Time frame: up to week 16
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 16 | 1365.2 nmol/L | Standard Deviation 403.12 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 16 | 967.6 nmol/L | Standard Deviation 255.78 |
Post Hoc
Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 20
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Time frame: up to week 20
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 20 | 1419.8 nmol/L | Standard Deviation 558.1 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 20 | 981.3 nmol/L | Standard Deviation 252.85 |
Post Hoc
Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 24
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Time frame: up to week 24
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 24 | 1355.3 nmol/L | Standard Deviation 364.85 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 24 | 949.2 nmol/L | Standard Deviation 256.26 |
Post Hoc
Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 4
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Time frame: up to week 4
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 4 | 1007.1 nmol/L | Standard Deviation 329.67 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 4 | 889.5 nmol/L | Standard Deviation 262.42 |
Post Hoc
Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 8
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Time frame: up to week 8
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF) | Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 8 | 1184.8 nmol/L | Standard Deviation 338.5 |
| Drospirenone (DRSP)/Ethinylestradiol (EE) | Mean Red Blood Cell (RBC) Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 8 | 970.4 nmol/L | Standard Deviation 252.79 |