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CompletedNCT01253187Updated Aug 7, 2013Results posted

Investigation of Bioequivalence of Ethinylestradiol (EE) and Drospirenone (DRSP) in Two Different Tablet Formulations: YAZ and YAZ + Levomefolate Calcium (Metafolin) & L-5-MTHF in Two Different Tablet Formulations: Levomefolate Calcium (Metafolin) and YAZ + Levomefolate Calcium (Metafolin)

A Phase 1 interventional study of EE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300) and EE 0.02 mg/DRSP 3 mg/L-5-MTHF Ca 0.451 mg (EE20/DRSP/L-5-MTHF Ca) in Contraception, sponsored by Bayer. Completed at 1 site in Netherlands. Open to female participants aged 18 Years to 38 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2013-08-07.

Sponsored by Bayer · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
44
Allocation
Randomized
Ages
18 Years to 38 Years
Sex
Female
01

Study summary

The purpose of this study is examine and compare the uptake of YAZ (oral contraceptive containing drospirenone and ethinylestradiol) with or without levomefolate calcium (Metafolin, a registered vitamin supplement) in the body and to examine and compare the uptake of levomefolate calcium with or without YAZ in the body, in healthy volunteers not using hormonal contraception

02

Conditions studied

  • Contraception
03

In context

Lead sponsor

Bayer is the lead sponsor of 1,643 studies on the registry; 57 are open to participants now.

Of its 209 completed or terminated interventional studies of FDA-regulated products, 129 (62%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 38 Years
Sexes eligible
Female
Accepts healthy volunteers
Yes

Inclusion criteria

  • Healthy female volunteer
  • Age: 18 - 38 years inclusive
  • Body mass index (BMI)1: ≥ 19 and \< 28 kg/m²
  • Regular cyclic menstrual periods at screening OR when using combined oral contraceptives during the recruitment period reporting of natural cyclic menstrual periods prior to their use
  • Willingness to use non-hormonal methods of contraception during the complete trial OR previous tubal ligation

Exclusion criteria

Exclusion Criteria:

  • incompletely cured pre-existing diseases for which it can be assumed that the absorption, distribution, metabolism, excretion and effect of the study drugs will not be normal
  • known or suspected sex-steroid influenced malignancies
  • endometrial hyperplasia; genital bleeding of unknown origin; uterus myomatosus
  • known or suspected tumors of the liver and pituitary
  • presence or history of severe hepatic disease as long as liver function values have not returned to normal
  • severe renal insufficiency or acute renal failure
  • thrombophlebitis, venous / arterial thromboembolic diseases; presence or history of prodromi of a thrombosis
  • other conditions that increase susceptibility to thromboembolic diseases
  • known neuropsychiatric diseases, especially known or suspected epilepsy, and/ or deficient status of folate or vitamin B12
  • use of any other medication within 2 cycles before first study drug administration which could affect the study aim
  • use of potassium sparing drugs; use of folic acid containing supplements or medicines or use of any medication within 2 cycles before first study drug administration known to interfere with folate metabolism
  • inadequate folate and/or Vitamin B12 status, clinically relevant deviations in red cell folate concentrations
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
None (open label)
Enrollment
44 participants (actual)

Study arms

  • Experimental
    EE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300)

    single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP)

    Drug: EE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300)

  • Experimental
    EE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca)

    single oral administration of 1 film-coated SHT04532B tablet, containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP) + 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[MTHF-Ca\])

    Drug: EE 0.02 mg/DRSP 3 mg/L-5-MTHF Ca 0.451 mg (EE20/DRSP/L-5-MTHF Ca)

  • Experimental
    L-5-MTHF Ca 0.451 mg (Metafolin)

    single oral administration of 1 coated SHT04532C tablet, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[MTHF-Ca\])

    Drug: L-5-MTHF 0.451mg (Metafolin)

Interventions

  • DrugEE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300)

    Treatment group A: Single 1 film-coated tablet (Ethinylestradiol \[EE\] 0.02mg / Drospirenone \[DRSP\] 3mg) taken orally under fasting condition at intervals of at least one menstrual cycle.

  • DrugEE 0.02 mg/DRSP 3 mg/L-5-MTHF Ca 0.451 mg (EE20/DRSP/L-5-MTHF Ca)

    Treatment group B: Single 1 film-coated tablet (Ethinylestradiol \[EE\] 0.02mg / Drospirenone \[DRSP\] 3mg / L-5-methyltetrahydrofolate \[L-5-MTHF\] 0.451mg) taken orally under fasting condition at intervals of at least one menstrual cycle.

  • DrugL-5-MTHF 0.451mg (Metafolin)

    Treatment group C: Single 1 coated tablet (L-5-methyltetrahydrofolate \[L-5-MTHF\] 0.451mg) taken orally under fasting condition at intervals of at least one menstrual cycle.

06

What researchers measure

Primary outcomes

  1. Mean Maximum Concentration (Cmax) of EE Incl. Bioequivalence (BE) Evaluation

    Cmax refers to the highest measured drug concentration which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample

    Time frame: up to 96 hours after administration

  2. Mean Area Under the Concentration-time Curve From Administration to the Last Measurement [AUC(0-tlast)] of EE Incl. Bioequivalence (BE) Evaluation

    The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample

    Time frame: up to 96 hours after administration

  3. Mean Maximum Concentration (Cmax) of DRSP Incl. Bioequivalence (BE) Evaluation

    Cmax refers to the highest measured drug concentration which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample

    Time frame: up to 168 hours after administration

  4. Mean Area Under the Concentration-time Curve From Administration to the Last Measurement [AUC(0-tlast)] of DRSP Incl. Bioequivalence (BE) Evaluation

    The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample

    Time frame: up to 168 hours after administration

  5. Mean Maximum Concentration (Cmax) of L-5-methyl-THF (Baseline Corrected) Incl. Bioequivalence (BE) Evaluation

    The baseline corrected Cmax is a measure of the highest measured drug concentration provided solely by the treatment after subtracting endogenous L-5-methyl-THF level. It is obtained by collecting a series of blood samples, measuring the concentrations of L-5-methyl-THF in each sample and by subtracting the pre-treatment concentration.

    Time frame: up to 12 hours after administration

  6. Mean Area Under the Concentration-time Curve From Administration to the Last Measurement [AUC(0-tlast)] of L-5-methyl-THF (Baseline Corrected) Incl. Bioequivalence (BE) Evaluation

    The baseline corrected AUC is a measure of the systemic drug exposure provided by the treatment excluding the endogenous L-5-methyl-THF level. It is obtained by collecting a series of blood samples, measuring the concentrations of L-5-methyl-THF in each sample and by subtracting the pre-treatment concentration.

    Time frame: up to 12 hours after administration

  7. Mean Maximum Concentration (Cmax) of L-5-methyl-THF (Baseline Uncorrected) Incl. Bioequivalence (BE) Evaluation

    The baseline uncorrected Cmax is a measure of the highest measured drug concentration including the endogenous L-5-methyl-THF level. It is obtained by collecting a series of blood samples and measuring the concentrations of L-5-methyl-THF in each sample.

    Time frame: up to 12 hours after administration

  8. Mean Area Under the Concentration-time Curve From Administration to the Last Measurement [AUC(0-tlast)] of L-5-methyl-THF (Baseline Uncorrected) Incl. Bioequivalence (BE) Evaluation

    The baseline uncorrected AUC is a measure of the systemic drug exposure provided by the treatment including the endogenous L-5-methyl-THF level. It is obtained by collecting a series of blood samples and measuring the concentrations of L-5-methyl-THF in each sample.

    Time frame: up to 12 hours after administration

Secondary outcomes

  1. Time to Reach Maximum Concentration (Tmax) of EE

    Tmax refers to the time after dosing when a drug attains its highest measurable concentration (Cmax). It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content

    Time frame: up to 96 hours after administration

  2. Mean Area Under the Concentration-time Curve From Administration up to 72h AUC(0-72h) of DRSP

    The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample

    Time frame: up to 72 hours after administration

  3. Time to Reach Maximum Concentration (Tmax) of DRSP

    Tmax refers to the time after dosing when a drug attains its highest measurable concentration (Cmax). It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content

    Time frame: up to 168 hours after administration

  4. Time to Reach Maximum Concentration (Tmax) of L-5-methyl-THF

    Tmax refers to the time after dosing when a drug attains its highest measurable concentration (Cmax). It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content

    Time frame: up to 12 hours after administration

07

Results

Posted May 9, 2011

Participant flow

Healthy young women, aged 18 - 38 years inclusive, who were nonsmokers were enrolled from 20 October 2006 to 13 September 2007 at one center in Germany.

Period 1
Participant flow — Period 1
MilestoneTreatment Sequence A: YAZ, EE20/DRSP/L-5-MTHF Ca, MetafolinTreatment Sequence B: YAZ, Metafolin, EE20/DRSP/L-5-MTHF CaTreatment Sequence C: EE20/DRSP/L-5-MTHF Ca, YAZ, MetafolinTreatment Sequence D: EE20/DRSP/L-5-MTHF Ca, Metafolin, YAZTreatment Sequence E: Metafolin, YAZ, EE20/DRSP/L-5-MTHF CaTreatment Sequence F: Metafolin, EE20/DRSP/L-5-MTHF Ca, YAZ
Started787796
Completed787796
Not completed000000
Period 2
Participant flow — Period 2
MilestoneTreatment Sequence A: YAZ, EE20/DRSP/L-5-MTHF Ca, MetafolinTreatment Sequence B: YAZ, Metafolin, EE20/DRSP/L-5-MTHF CaTreatment Sequence C: EE20/DRSP/L-5-MTHF Ca, YAZ, MetafolinTreatment Sequence D: EE20/DRSP/L-5-MTHF Ca, Metafolin, YAZTreatment Sequence E: Metafolin, YAZ, EE20/DRSP/L-5-MTHF CaTreatment Sequence F: Metafolin, EE20/DRSP/L-5-MTHF Ca, YAZ
Started787796
Completed787786
Not completed000010
Withdrew: Withdrawal by subject000010
Period 3
Participant flow — Period 3
MilestoneTreatment Sequence A: YAZ, EE20/DRSP/L-5-MTHF Ca, MetafolinTreatment Sequence B: YAZ, Metafolin, EE20/DRSP/L-5-MTHF CaTreatment Sequence C: EE20/DRSP/L-5-MTHF Ca, YAZ, MetafolinTreatment Sequence D: EE20/DRSP/L-5-MTHF Ca, Metafolin, YAZTreatment Sequence E: Metafolin, YAZ, EE20/DRSP/L-5-MTHF CaTreatment Sequence F: Metafolin, EE20/DRSP/L-5-MTHF Ca, YAZ
Started787786
Completed677776
Not completed110010
Withdrew: Pregnancy100000
Withdrew: Difficulty with blood sampling010000
Withdrew: Non-compliance000010

Outcome measures

PrimaryMean Maximum Concentration (Cmax) of EE Incl. Bioequivalence (BE) Evaluation

Cmax refers to the highest measured drug concentration which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample

Time frame:
up to 96 hours after administration
Reported as:
Geometric mean · pg/mL
Mean Maximum Concentration (Cmax) of EE Incl. Bioequivalence (BE) Evaluation
pg/mLEE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300)EE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca)
Mean Maximum Concentration (Cmax) of EE Incl. Bioequivalence (BE) Evaluation39.6 (35.7 to 44.0)41.9 (37.6 to 46.7)
Statistical analysis
  • EE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300) vs EE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca) · ANOVA · Mean ratio: 106.03 · 90% CI 98.86 to 113.72Point estimate for the ratio \[(EE20/DRSP/L-5-MTHF Ca) / YAZ\]. Bioequivalence is established if the 90% confidence interval fall within the equivalence interval limits of 80-125%
PrimaryMean Area Under the Concentration-time Curve From Administration to the Last Measurement [AUC(0-tlast)] of EE Incl. Bioequivalence (BE) Evaluation

The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample

Time frame:
up to 96 hours after administration
Reported as:
Geometric mean · pg·h/mL
Mean Area Under the Concentration-time Curve From Administration to the Last Measurement [AUC(0-tlast)] of EE Incl. Bioequivalence (BE) Evaluation
pg·h/mLEE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300)EE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca)
Mean Area Under the Concentration-time Curve From Administration to the Last Measurement [AUC(0-tlast)] of EE Incl. Bioequivalence (BE) Evaluation358 (320 to 400)370 (332 to 412)
Statistical analysis
  • EE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300) vs EE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca) · ANOVA · Mean ratio: 103.47 · 90% CI 99.16 to 107.98Point estimate for the ratio \[(EE20/DRSP/L-5-MTHF Ca) / YAZ\]. Bioequivalence is established if the 90% confidence interval fall within the equivalence interval limits of 80-125%
PrimaryMean Maximum Concentration (Cmax) of DRSP Incl. Bioequivalence (BE) Evaluation

Cmax refers to the highest measured drug concentration which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample

Time frame:
up to 168 hours after administration
Reported as:
Geometric mean · ng/mL
Mean Maximum Concentration (Cmax) of DRSP Incl. Bioequivalence (BE) Evaluation
ng/mLEE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300)EE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca)
Mean Maximum Concentration (Cmax) of DRSP Incl. Bioequivalence (BE) Evaluation25.4 (23.3 to 27.7)26.7 (24.5 to 29.1)
Statistical analysis
  • EE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300) vs EE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca) · ANOVA · Mean ratio: 105.24 · 90% CI 97.30 to 113.83Point estimate for the ratio \[(EE20/DRSP/L-5-MTHF Ca) / YAZ\]. Bioequivalence is established if the 90% confidence interval fall within the equivalence interval limits of 80-125%
PrimaryMean Area Under the Concentration-time Curve From Administration to the Last Measurement [AUC(0-tlast)] of DRSP Incl. Bioequivalence (BE) Evaluation

The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample

Time frame:
up to 168 hours after administration
Reported as:
Geometric mean · ng·h/mL
Mean Area Under the Concentration-time Curve From Administration to the Last Measurement [AUC(0-tlast)] of DRSP Incl. Bioequivalence (BE) Evaluation
ng·h/mLEE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300)EE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca)
Mean Area Under the Concentration-time Curve From Administration to the Last Measurement [AUC(0-tlast)] of DRSP Incl. Bioequivalence (BE) Evaluation386 (352 to 424)383 (346 to 424)
Statistical analysis
  • EE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300) vs EE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca) · ANOVA · Mean ratio: 100.48 · 90% CI 97.28 to 103.79Point estimate for the ratio \[(EE20/DRSP/L-5-MTHF Ca) / YAZ\]. Bioequivalence is established if the 90% confidence interval fall within the equivalence interval limits of 80-125%
PrimaryMean Maximum Concentration (Cmax) of L-5-methyl-THF (Baseline Corrected) Incl. Bioequivalence (BE) Evaluation

The baseline corrected Cmax is a measure of the highest measured drug concentration provided solely by the treatment after subtracting endogenous L-5-methyl-THF level. It is obtained by collecting a series of blood samples, measuring the concentrations of L-5-methyl-THF in each sample and by subtracting the pre-treatment concentration.

Time frame:
up to 12 hours after administration
Reported as:
Geometric mean · nmol/L
Mean Maximum Concentration (Cmax) of L-5-methyl-THF (Baseline Corrected) Incl. Bioequivalence (BE) Evaluation
nmol/LEE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca)L-5-MTHF Ca 0.451 mg (Metafolin)
Mean Maximum Concentration (Cmax) of L-5-methyl-THF (Baseline Corrected) Incl. Bioequivalence (BE) Evaluation44.3 (40.0 to 49.2)44.2 (39.1 to 49.9)
Statistical analysis
  • EE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca) vs L-5-MTHF Ca 0.451 mg (Metafolin) · ANOVA · Mean ratio: 99.88 · 90% CI 91.24 to 109.34Point estimate for the ratio \[(EE20/DRSP/L-5-MTHF Ca) / Metafolin\]. Bioequivalence is established if the 90% confidence interval fall within the equivalence interval limits of 80-125%
PrimaryMean Area Under the Concentration-time Curve From Administration to the Last Measurement [AUC(0-tlast)] of L-5-methyl-THF (Baseline Corrected) Incl. Bioequivalence (BE) Evaluation

The baseline corrected AUC is a measure of the systemic drug exposure provided by the treatment excluding the endogenous L-5-methyl-THF level. It is obtained by collecting a series of blood samples, measuring the concentrations of L-5-methyl-THF in each sample and by subtracting the pre-treatment concentration.

Time frame:
up to 12 hours after administration
Reported as:
Geometric mean · nmol·h/L
Mean Area Under the Concentration-time Curve From Administration to the Last Measurement [AUC(0-tlast)] of L-5-methyl-THF (Baseline Corrected) Incl. Bioequivalence (BE) Evaluation
nmol·h/LEE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca)L-5-MTHF Ca 0.451 mg (Metafolin)
Mean Area Under the Concentration-time Curve From Administration to the Last Measurement [AUC(0-tlast)] of L-5-methyl-THF (Baseline Corrected) Incl. Bioequivalence (BE) Evaluation214 (195 to 235)217 (199 to 237)
Statistical analysis
  • EE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca) vs L-5-MTHF Ca 0.451 mg (Metafolin) · ANOVA · Mean ratio: 98.16 · 90% CI 93.95 to 102.57Point estimate for the ratio \[(EE20/DRSP/L-5-MTHF Ca) / Metafolin\]. Bioequivalence is established if the 90% confidence interval fall within the equivalence interval limits of 80-125%
PrimaryMean Maximum Concentration (Cmax) of L-5-methyl-THF (Baseline Uncorrected) Incl. Bioequivalence (BE) Evaluation

The baseline uncorrected Cmax is a measure of the highest measured drug concentration including the endogenous L-5-methyl-THF level. It is obtained by collecting a series of blood samples and measuring the concentrations of L-5-methyl-THF in each sample.

Time frame:
up to 12 hours after administration
Reported as:
Geometric mean · nmol/L
Mean Maximum Concentration (Cmax) of L-5-methyl-THF (Baseline Uncorrected) Incl. Bioequivalence (BE) Evaluation
nmol/LEE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca)L-5-MTHF Ca 0.451 mg (Metafolin)
Mean Maximum Concentration (Cmax) of L-5-methyl-THF (Baseline Uncorrected) Incl. Bioequivalence (BE) Evaluation57.9 (52.6 to 63.6)57.7 (51.7 to 64.4)
Statistical analysis
  • EE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca) vs L-5-MTHF Ca 0.451 mg (Metafolin) · ANOVA · Mean ratio: 100.28 · 90% CI 93.15 to 107.95Point estimate for the ratio \[(EE20/DRSP/L-5-MTHF Ca) / Metafolin\]. Bioequivalence is established if the 90% confidence interval fall within the equivalence interval limits of 80-125%
PrimaryMean Area Under the Concentration-time Curve From Administration to the Last Measurement [AUC(0-tlast)] of L-5-methyl-THF (Baseline Uncorrected) Incl. Bioequivalence (BE) Evaluation

The baseline uncorrected AUC is a measure of the systemic drug exposure provided by the treatment including the endogenous L-5-methyl-THF level. It is obtained by collecting a series of blood samples and measuring the concentrations of L-5-methyl-THF in each sample.

Time frame:
up to 12 hours after administration
Reported as:
Geometric mean · nmol·h/L
Mean Area Under the Concentration-time Curve From Administration to the Last Measurement [AUC(0-tlast)] of L-5-methyl-THF (Baseline Uncorrected) Incl. Bioequivalence (BE) Evaluation
nmol·h/LEE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca)L-5-MTHF Ca 0.451 mg (Metafolin)
Mean Area Under the Concentration-time Curve From Administration to the Last Measurement [AUC(0-tlast)] of L-5-methyl-THF (Baseline Uncorrected) Incl. Bioequivalence (BE) Evaluation370 (333 to 412)370 (334 to 411)
Statistical analysis
  • EE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca) vs L-5-MTHF Ca 0.451 mg (Metafolin) · ANOVA · Mean ratio: 99.88 · 90% CI 95.38 to 104.58Point estimate for the ratio \[(EE20/DRSP/L-5-MTHF Ca) / Metafolin\]. Bioequivalence is established if the 90% confidence interval fall within the equivalence interval limits of 80-125%
SecondaryTime to Reach Maximum Concentration (Tmax) of EE

Tmax refers to the time after dosing when a drug attains its highest measurable concentration (Cmax). It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content

Time frame:
up to 96 hours after administration
Reported as:
Median · hours
Time to Reach Maximum Concentration (Tmax) of EE
hoursEE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300)EE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca)
Time to Reach Maximum Concentration (Tmax) of EE1.50 (0.50 to 4.00)1.52 (1.00 to 4.18)
SecondaryMean Area Under the Concentration-time Curve From Administration up to 72h AUC(0-72h) of DRSP

The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample

Time frame:
up to 72 hours after administration
Reported as:
Geometric mean · ng·h/mL
Mean Area Under the Concentration-time Curve From Administration up to 72h AUC(0-72h) of DRSP
ng·h/mLEE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300)EE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca)
Mean Area Under the Concentration-time Curve From Administration up to 72h AUC(0-72h) of DRSP350 (328 to 373)344 (319 to 371)
Statistical analysis
  • EE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300) vs EE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca) · ANOVA · Mean ratio: 100.30 · 90% CI 97.65 to 103.02Point estimate for the ratio \[(EE20/DRSP/L-5-MTHF Ca) / YAZ\]. Bioequivalence is established if the 90% confidence interval fall within the equivalence interval limits of 80-125%
SecondaryTime to Reach Maximum Concentration (Tmax) of DRSP

Tmax refers to the time after dosing when a drug attains its highest measurable concentration (Cmax). It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content

Time frame:
up to 168 hours after administration
Reported as:
Median · hours
Time to Reach Maximum Concentration (Tmax) of DRSP
hoursEE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300)EE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca)
Time to Reach Maximum Concentration (Tmax) of DRSP2.00 (0.50 to 4.00)2.00 (0.50 to 4.10)
SecondaryTime to Reach Maximum Concentration (Tmax) of L-5-methyl-THF

Tmax refers to the time after dosing when a drug attains its highest measurable concentration (Cmax). It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content

Time frame:
up to 12 hours after administration
Reported as:
Median · hours
Time to Reach Maximum Concentration (Tmax) of L-5-methyl-THF
hoursEE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca)L-5-MTHF Ca 0.451 mg (Metafolin)
Time to Reach Maximum Concentration (Tmax) of L-5-methyl-THF0.50 (0.00 to 4.00)0.50 (0.50 to 2.00)

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
EE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300)—0/43 (0%)37/43 (86%)
EE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca)—0/41 (0%)30/41 (73.2%)
L-5-MTHF Ca 0.451 mg (Metafolin)—0/43 (0%)34/43 (79.1%)
Most frequent other events
Showing 10 of 68
Most frequent other events
EventEE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300)EE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca)L-5-MTHF Ca 0.451 mg (Metafolin)
HeadacheNervous system disorders15/439/4111/43
NauseaGastrointestinal disorders6/4311/415/43
MetrorrhagiaReproductive system and breast disorders10/439/410/43
Serum ferritin decreasedInvestigations7/436/418/43
DiarrhoeaGastrointestinal disorders7/435/412/43
Syncope vasovagalNervous system disorders7/433/412/43
FatigueGeneral disorders5/435/412/43
Abdominal painGastrointestinal disorders2/434/411/43
VomitingGastrointestinal disorders1/434/412/43
Abdominal discomfortGastrointestinal disorders4/432/411/43

Baseline characteristics

Age Continuous
Age Continuous(Years)Entire Study Population
Mean26.3 ± 6.33
Sex: Female, Male
Sex: Female, Male(Participants)Entire Study Population
Female44
Male0
08

Study locations

1 site
  • Dinox B.V.
    Groningen, 9713GZ, Netherlands
09

References and documents

Publications

  • Blode H, Klipping C, Richard F, Trummer D, Rohde B, Diefenbach K. Bioequivalence study of an oral contraceptive containing ethinylestradiol/drospirenone/levomefolate calcium relative to ethinylestradiol/drospirenone and to levomefolate calcium alone. Contraception. 2012 Feb;85(2):177-84. doi: 10.1016/j.contraception.2011.05.015. Epub 2011 Jul 19. PubMed 22067789 ↗
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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 7, 2013, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT01253187
Lead sponsor
Bayer
First posted
Dec 3, 2010
Start date
Oct 2006
Primary completion
Sep 2007
Completion
Sep 2007
Results posted
May 9, 2011
Last update
Aug 7, 2013

Study contacts

Bayer Study Director
study director · Bayer

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Aug 2013. You cannot join it, but the record below documents what was studied.

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Discussion

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