Trial Outcomes & Findings for Efficacy and Safety Study for an Oral Contraceptive Containing Folate (NCT NCT00468481)
NCT ID: NCT00468481
Last Updated: 2014-04-23
Results Overview
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
COMPLETED
PHASE3
385 participants
Week 24
2014-04-23
Participant Flow
572 subjects screened; 187 subjects screen failed; 385 subjects randomized
Participant milestones
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
1 tablet 0.020 mg EE/3.0 mg DRSP \[YAZ\] given orally/daily for 24 days followed by 1 placebo tablet given orally/daily for 4 days over a time period of 24 weeks
|
|---|---|---|
|
Overall Study
STARTED
|
291
|
94
|
|
Overall Study
Subjects Treated
|
285
|
94
|
|
Overall Study
COMPLETED
|
203
|
70
|
|
Overall Study
NOT COMPLETED
|
88
|
24
|
Reasons for withdrawal
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
1 tablet 0.020 mg EE/3.0 mg DRSP \[YAZ\] given orally/daily for 24 days followed by 1 placebo tablet given orally/daily for 4 days over a time period of 24 weeks
|
|---|---|---|
|
Overall Study
Adverse Event
|
13
|
3
|
|
Overall Study
Lost to Follow-up
|
25
|
8
|
|
Overall Study
Pregnancy
|
2
|
0
|
|
Overall Study
Protocol Violation
|
18
|
8
|
|
Overall Study
Withdrawal by Subject
|
12
|
3
|
|
Overall Study
susp/diag malignant/premalignant disease
|
1
|
0
|
|
Overall Study
Prohibited Medication
|
1
|
1
|
|
Overall Study
Egg Donor
|
1
|
0
|
|
Overall Study
Moved out of area
|
4
|
1
|
|
Overall Study
Non-Compliance
|
5
|
0
|
|
Overall Study
Other
|
6
|
0
|
Baseline Characteristics
Efficacy and Safety Study for an Oral Contraceptive Containing Folate
Baseline characteristics by cohort
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=285 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=94 Participants
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
n=379 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
24.8 years
n=5 Participants
|
24.6 years
n=7 Participants
|
24.7 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
285 Participants
n=5 Participants
|
94 Participants
n=7 Participants
|
379 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Week 24Population: 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.
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=124 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=45 Participants
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
|
|---|---|---|
|
Red Blood Cell (RBC) Folate Level at 24 Weeks
|
1406.91 nmol/L
Interval 1354.13 to 1459.68
|
1022.21 nmol/L
Interval 934.6 to 1109.82
|
PRIMARY outcome
Timeframe: Week 24Population: 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.
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=196 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=66 Participants
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
|
|---|---|---|
|
Plasma Folate Level at 24 Weeks
|
60.55 nmol/L
Interval 58.13 to 62.97
|
41.67 nmol/L
Interval 37.5 to 45.85
|
SECONDARY outcome
Timeframe: Baseline and week 24Population: 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.
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
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=124 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=45 Participants
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
|
|---|---|---|
|
Mean Neural Tube Defect (NTD) Risk Reduction at Week 24
|
-0.51 per 1000 birth
Standard Deviation 0.41
|
-0.03 per 1000 birth
Standard Deviation 0.26
|
SECONDARY outcome
Timeframe: baseline and up to week 4Population: 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
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=125 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=43 Participants
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
|
|---|---|---|
|
Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 4
|
110.9 nmol/L
Standard Deviation 207.28
|
-37.6 nmol/L
Standard Deviation 195.88
|
SECONDARY outcome
Timeframe: baseline and up to week 8Population: 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.
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=122 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=43 Participants
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
|
|---|---|---|
|
Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 8
|
310.3 nmol/L
Standard Deviation 231.47
|
68.2 nmol/L
Standard Deviation 155.26
|
SECONDARY outcome
Timeframe: baseline and up to week 12Population: 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.
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=127 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=41 Participants
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
|
|---|---|---|
|
Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 12
|
405.8 nmol/L
Standard Deviation 243.88
|
86.5 nmol/L
Standard Deviation 177.81
|
SECONDARY outcome
Timeframe: baseline and up to week 16Population: 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.
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=120 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=46 Participants
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
|
|---|---|---|
|
Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 16
|
448.9 nmol/L
Standard Deviation 280.37
|
68.0 nmol/L
Standard Deviation 186.44
|
SECONDARY outcome
Timeframe: baseline and up to week 20Population: 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.
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=123 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=44 Participants
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
|
|---|---|---|
|
Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 20
|
452.7 nmol/L
Standard Deviation 284.64
|
64.6 nmol/L
Standard Deviation 194.89
|
SECONDARY outcome
Timeframe: baseline and up to week 4Population: 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
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=192 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=65 Participants
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
|
|---|---|---|
|
Mean Change From Baseline in Plasma Folate Levels at Week 4
|
15.2 nmol/L
Standard Deviation 22.07
|
0.6 nmol/L
Standard Deviation 14.29
|
SECONDARY outcome
Timeframe: baseline and up to week 8Population: 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
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=193 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=66 Participants
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
|
|---|---|---|
|
Mean Change From Baseline in Plasma Folate Levels at Week 8
|
18.4 µg/L
Standard Deviation 19.17
|
2.2 µg/L
Standard Deviation 14.63
|
SECONDARY outcome
Timeframe: baseline and up to week 12Population: 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.
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=194 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=66 Participants
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
|
|---|---|---|
|
Mean Change From Baseline in Plasma Folate Levels at Week 12
|
17.6 nmol/L
Standard Deviation 20.1
|
0.3 nmol/L
Standard Deviation 15.24
|
SECONDARY outcome
Timeframe: baseline and up to week 16Population: 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.
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=194 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=65 Participants
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
|
|---|---|---|
|
Mean Change From Baseline in Plasma Folate Levels at Week 16
|
17.6 nmol/L
Standard Deviation 12.43
|
2.4 nmol/L
Standard Deviation 16.44
|
SECONDARY outcome
Timeframe: baseline and up to week 20Population: 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.
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=193 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=66 Participants
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
|
|---|---|---|
|
Mean Change From Baseline in Plasma Folate Levels at Week 20
|
15.1 nmol/L
Standard Deviation 22.71
|
-1.6 nmol/L
Standard Deviation 15.65
|
SECONDARY outcome
Timeframe: baseline and up to week 4Population: 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
Homocysteine concentrations in plasma were determined by Fluorescence Polarization Immunoassays (FPIA) using the Abbot AxSym analyzer in a clinical laboratory setting.
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=194 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=65 Participants
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
|
|---|---|---|
|
Mean Change From Baseline in Plasma Homocysteine Levels at Week 4
|
0 µg/L
Standard Deviation 1.04
|
0 µg/L
Standard Deviation 0.69
|
SECONDARY outcome
Timeframe: baseline and up to week 8Population: 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.
Homocysteine concentrations in plasma were determined by Fluorescence Polarization Immunoassays (FPIA) using the Abbot AxSym analyzer in a clinical laboratory setting.
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=195 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=66 Participants
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
|
|---|---|---|
|
Mean Change From Baseline in Plasma Homocysteine Levels at Week 8
|
-0.2 µg/L
Standard Deviation 0.9
|
0 µg/L
Standard Deviation 1
|
SECONDARY outcome
Timeframe: baseline and up to week 12Population: 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.
Homocysteine concentrations in plasma were determined by Fluorescence Polarization Immunoassays (FPIA) using the Abbot AxSym analyzer in a clinical laboratory setting.
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=196 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=66 Participants
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
|
|---|---|---|
|
Mean Change From Baseline in Plasma Homocysteine Levels at Week 12
|
-0.3 µg/L
Standard Deviation 1.07
|
0 µg/L
Standard Deviation 0.93
|
SECONDARY outcome
Timeframe: baseline and up to week 16Population: 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.
Homocysteine concentrations in plasma were determined by Fluorescence Polarization Immunoassays (FPIA) using the Abbot AxSym analyzer in a clinical laboratory setting.
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=194 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=65 Participants
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
|
|---|---|---|
|
Mean Change From Baseline in Plasma Homocysteine Levels at Week 16
|
-0.2 µg/L
Standard Deviation 1.02
|
-0.1 µg/L
Standard Deviation 0.93
|
SECONDARY outcome
Timeframe: baseline and up to week 20Population: 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.
Homocysteine concentrations in plasma were determined by Fluorescence Polarization Immunoassays (FPIA) using the Abbot AxSym analyzer in a clinical laboratory setting.
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=195 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=66 Participants
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
|
|---|---|---|
|
Mean Change From Baseline in Plasma Homocysteine Levels at Week 20
|
-0.2 µg/L
Standard Deviation 1.07
|
-0.2 µg/L
Standard Deviation 0.91
|
SECONDARY outcome
Timeframe: baseline and up to week 24Population: 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.
Homocysteine concentrations in plasma were determined by Fluorescence Polarization Immunoassays (FPIA) using the Abbot AxSym analyzer in a clinical laboratory setting.
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=195 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=66 Participants
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
|
|---|---|---|
|
Mean Change From Baseline in Plasma Homocysteine Levels at Week 24
|
-0.3 µg/L
Standard Deviation 0.93
|
0.1 µg/L
Standard Deviation 1.24
|
POST_HOC outcome
Timeframe: 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
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=90 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=40 Participants
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
|
|---|---|---|
|
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
|
915.1 nmol/L
Standard Deviation 233.97
|
POST_HOC outcome
Timeframe: 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
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=54 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=12 Participants
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
|
|---|---|---|
|
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
|
1345.0 nmol/L
Standard Deviation 301.76
|
POST_HOC outcome
Timeframe: up to week 4Population: 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
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=80 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=35 Participants
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
|
|---|---|---|
|
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
|
889.5 nmol/L
Standard Deviation 262.42
|
POST_HOC outcome
Timeframe: up to week 4Population: 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.
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=50 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=9 Participants
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
|
|---|---|---|
|
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
|
1256.1 nmol/L
Standard Deviation 190.89
|
POST_HOC outcome
Timeframe: up to week 8Population: 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.
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=76 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=33 Participants
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
|
|---|---|---|
|
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
|
970.4 nmol/L
Standard Deviation 252.79
|
POST_HOC outcome
Timeframe: up to week 8Population: 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.
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=50 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=10 Participants
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
|
|---|---|---|
|
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
|
1407.6 nmol/L
Standard Deviation 290.18
|
POST_HOC outcome
Timeframe: up to week 12Population: 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.
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=79 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=33 Participants
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
|
|---|---|---|
|
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
|
1025.2 nmol/L
Standard Deviation 287.55
|
POST_HOC outcome
Timeframe: up to week 12Population: 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.
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=50 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=10 Participants
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
|
|---|---|---|
|
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
|
1378.4 nmol/L
Standard Deviation 375.15
|
POST_HOC outcome
Timeframe: up to week 16Population: 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.
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=76 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=35 Participants
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
|
|---|---|---|
|
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
|
967.6 nmol/L
Standard Deviation 255.78
|
POST_HOC outcome
Timeframe: up to week 16Population: 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.
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=50 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=11 Participants
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
|
|---|---|---|
|
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
|
1454.7 nmol/L
Standard Deviation 355.5
|
POST_HOC outcome
Timeframe: up to week 20Population: 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.
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=78 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=33 Participants
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
|
|---|---|---|
|
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
|
981.3 nmol/L
Standard Deviation 252.85
|
POST_HOC outcome
Timeframe: up to week 20Population: 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.
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=49 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=13 Participants
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
|
|---|---|---|
|
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
|
1435.9 nmol/L
Standard Deviation 319.33
|
POST_HOC outcome
Timeframe: up to week 24Population: 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.
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=87 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=37 Participants
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
|
|---|---|---|
|
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
|
949.2 nmol/L
Standard Deviation 256.26
|
POST_HOC outcome
Timeframe: up to week 24Population: 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.
RBC folate=(\[whole blood folate\*100\]-\[plasma folate\*(100-hematocrit)\])/hematocrit
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=51 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=10 Participants
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
|
|---|---|---|
|
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
|
1316.1 nmol/L
Standard Deviation 237.44
|
POST_HOC outcome
Timeframe: 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
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=120 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=47 Participants
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
|
|---|---|---|
|
Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Baseline
|
41.7 nmol/L
Standard Deviation 16.2
|
41.5 nmol/L
Standard Deviation 15.57
|
POST_HOC outcome
Timeframe: 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
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=76 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=19 Participants
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
|
|---|---|---|
|
Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Baseline
|
50.3 nmol/L
Standard Deviation 18.45
|
47.1 nmol/L
Standard Deviation 17.3
|
POST_HOC outcome
Timeframe: up to week 4Population: 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
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=119 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=47 Participants
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
|
|---|---|---|
|
Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 4
|
59.6 nmol/L
Standard Deviation 24.83
|
43.1 nmol/L
Standard Deviation 17.98
|
POST_HOC outcome
Timeframe: up to week 4Population: 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.
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=73 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=18 Participants
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
|
|---|---|---|
|
Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 4
|
60.4 nmol/L
Standard Deviation 27.56
|
45.9 nmol/L
Standard Deviation 21.19
|
POST_HOC outcome
Timeframe: up to week 8Population: 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.
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=118 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=47 Participants
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
|
|---|---|---|
|
Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 8
|
60.8 nmol/L
Standard Deviation 22.41
|
41.8 nmol/L
Standard Deviation 14.96
|
POST_HOC outcome
Timeframe: up to week 8Population: 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.
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=75 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=19 Participants
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
|
|---|---|---|
|
Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 8
|
68.1 nmol/L
Standard Deviation 26.60
|
54.1 nmol/L
Standard Deviation 30.16
|
POST_HOC outcome
Timeframe: up to week 12Population: 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.
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=119 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=47 Participants
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
|
|---|---|---|
|
Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 12
|
59.5 nmol/L
Standard Deviation 20.39
|
42.3 nmol/L
Standard Deviation 17.19
|
POST_HOC outcome
Timeframe: up to week 12Population: 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.
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=75 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=19 Participants
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
|
|---|---|---|
|
Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 12
|
67.4 nmol/L
Standard Deviation 23.69
|
46.4 nmol/L
Standard Deviation 17.55
|
POST_HOC outcome
Timeframe: up to week 16Population: 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.
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=118 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=46 Participants
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
|
|---|---|---|
|
Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 16
|
59.4 nmol/L
Standard Deviation 18.89
|
43.2 nmol/L
Standard Deviation 18.4
|
POST_HOC outcome
Timeframe: up to week 16Population: 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.
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=76 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=19 Participants
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
|
|---|---|---|
|
Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 16
|
67.5 nmol/L
Standard Deviation 26.38
|
51.8 nmol/L
Standard Deviation 21.08
|
POST_HOC outcome
Timeframe: up to week 20Population: 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.
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=118 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=47 Participants
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
|
|---|---|---|
|
Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 20
|
59.8 nmol/L
Standard Deviation 21.11
|
39.7 nmol/L
Standard Deviation 16.74
|
POST_HOC outcome
Timeframe: up to week 20Population: 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.
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=75 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=19 Participants
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
|
|---|---|---|
|
Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 20
|
61.5 nmol/L
Standard Deviation 24.16
|
45.9 nmol/L
Standard Deviation 14.54
|
POST_HOC outcome
Timeframe: up to week 24Population: 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.
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=120 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=47 Participants
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
|
|---|---|---|
|
Mean Plasma Folate Levels by Additional Folate Supplementation (Without Additional Folate Supplementation) at Week 24
|
58.7 nmol/L
Standard Deviation 17.73
|
39.8 nmol/L
Standard Deviation 18.02
|
POST_HOC outcome
Timeframe: up to week 24Population: 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.
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Outcome measures
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=76 Participants
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=19 Participants
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
|
|---|---|---|
|
Mean Plasma Folate Levels by Additional Folate Supplementation (With Additional Folate Supplementation) at Week 24
|
64.0 nmol/L
Standard Deviation 22.61
|
43.7 nmol/L
Standard Deviation 16.5
|
Adverse Events
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
Drospirenone (DRSP)/Ethinylestradiol (EE)
Serious adverse events
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=285 participants at risk
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=94 participants at risk
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
|
|---|---|---|
|
Infections and infestations
Pneumonia
|
0.35%
1/285 • Number of events 1
|
0.00%
0/94
|
|
Investigations
Human papilloma virus test positive
|
0.35%
1/285 • Number of events 1
|
0.00%
0/94
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cervix carcinoma stage 0
|
0.35%
1/285 • Number of events 1
|
0.00%
0/94
|
|
Reproductive system and breast disorders
Cervical dysplasia
|
0.35%
1/285 • Number of events 1
|
0.00%
0/94
|
Other adverse events
| Measure |
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
n=285 participants at risk
1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks
|
Drospirenone (DRSP)/Ethinylestradiol (EE)
n=94 participants at risk
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
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
0.35%
1/285 • Number of events 1
|
3.2%
3/94 • Number of events 3
|
|
Infections and infestations
Bronchitis
|
2.1%
6/285 • Number of events 6
|
1.1%
1/94 • Number of events 1
|
|
Infections and infestations
Influenza
|
2.1%
6/285 • Number of events 6
|
3.2%
3/94 • Number of events 3
|
|
Infections and infestations
Nasopharyngitis
|
3.9%
11/285 • Number of events 11
|
2.1%
2/94 • Number of events 2
|
|
Infections and infestations
Pharyngitis
|
0.35%
1/285 • Number of events 1
|
2.1%
2/94 • Number of events 2
|
|
Infections and infestations
Sinusitis
|
3.2%
9/285 • Number of events 9
|
3.2%
3/94 • Number of events 3
|
|
Infections and infestations
Upper respiratory tract infection
|
10.5%
30/285 • Number of events 32
|
9.6%
9/94 • Number of events 10
|
|
Infections and infestations
Urinary tract infection
|
3.5%
10/285 • Number of events 11
|
2.1%
2/94 • Number of events 2
|
|
Investigations
Blood cholinesterase decreased
|
0.35%
1/285 • Number of events 1
|
2.1%
2/94 • Number of events 2
|
|
Investigations
Blood triglycerides increased
|
0.00%
0/285
|
2.1%
2/94 • Number of events 2
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.70%
2/285 • Number of events 2
|
2.1%
2/94 • Number of events 2
|
|
Investigations
Low density lipoprotein increased
|
6.0%
17/285 • Number of events 17
|
8.5%
8/94 • Number of events 8
|
|
Investigations
Prothrombin level decreased
|
0.00%
0/285
|
2.1%
2/94 • Number of events 2
|
|
Investigations
Human papilloma virus test positive
|
3.5%
10/285 • Number of events 10
|
2.1%
2/94 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.35%
1/285 • Number of events 1
|
2.1%
2/94 • Number of events 2
|
|
Nervous system disorders
Headache
|
2.1%
6/285 • Number of events 9
|
4.3%
4/94 • Number of events 6
|
|
Nervous system disorders
Migraine
|
0.70%
2/285 • Number of events 3
|
2.1%
2/94 • Number of events 2
|
|
Psychiatric disorders
Anxiety
|
0.35%
1/285 • Number of events 1
|
3.2%
3/94 • Number of events 3
|
|
Reproductive system and breast disorders
Cervical dysplasia
|
3.5%
10/285 • Number of events 10
|
4.3%
4/94 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
1.8%
5/285 • Number of events 5
|
5.3%
5/94 • Number of events 5
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
0.00%
0/285
|
2.1%
2/94 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/285
|
2.1%
2/94 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Rash
|
1.8%
5/285 • Number of events 5
|
5.3%
5/94 • Number of events 5
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60