Trial Outcomes & Findings for 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) (NCT NCT01253187)
NCT ID: NCT01253187
Last Updated: 2013-08-07
Results Overview
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
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
44 participants
Primary outcome timeframe
up to 96 hours after administration
Results posted on
2013-08-07
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.
77 female volunteers were screened according to the inclusion and exclusion criteria to determine that the volunteer was in a good state of health and appropriate for inclusion in the study, and 44 volunteers were randomized at one center.
Participant milestones
| Measure |
Treatment Sequence A: YAZ, EE20/DRSP/L-5-MTHF Ca, Metafolin
YAZ for Period 1; EE20/DRSP/L-5-MTHF Ca for Period 2; Metafolin for Period 3. YAZ: single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP) / 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 \[MTHF-Ca\]) / Metafolin: single oral administration of 1 coated SHT04532C tablet, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[MTHF-Ca\]).
|
Treatment Sequence B: YAZ, Metafolin, EE20/DRSP/L-5-MTHF Ca
YAZ for Period 1; Metafolin for Period 2; EE20/DRSP/L-5-MTHF Ca for Period 3. YAZ: single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP) / Metafolin: single oral administration of 1 coated SHT04532C tablet, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[MTHF-Ca\]) / 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 \[MTHF-Ca\]).
|
Treatment Sequence C: EE20/DRSP/L-5-MTHF Ca, YAZ, Metafolin
EE20/DRSP/L-5-MTHF Ca for Period 1; YAZ for Period 2; Metafolin for Period 3. 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 \[MTHF-Ca\]) / YAZ: single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP) / Metafolin: single oral administration of 1 coated SHT04532C tablet, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[MTHF-Ca\]).
|
Treatment Sequence D: EE20/DRSP/L-5-MTHF Ca, Metafolin, YAZ
EE20/DRSP/L-5-MTHF Ca for Period 1; Metafolin for Period 2; YAZ for Period 3. 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 \[MTHF-Ca\]) / Metafolin: single oral administration of 1 coated SHT04532C tablet, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[MTHF-Ca\]) / YAZ: single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP).
|
Treatment Sequence E: Metafolin, YAZ, EE20/DRSP/L-5-MTHF Ca
Metafolin for Period 1; YAZ for Period 2; EE20/DRSP/L-5-MTHF Ca for Period 3. Metafolin: single oral administration of 1 coated SHT04532C tablet, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[MTHF-Ca\]) / YAZ: single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP) / 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 \[MTHF-Ca\]).
|
Treatment Sequence F: Metafolin, EE20/DRSP/L-5-MTHF Ca, YAZ
Metafolin for Period 1; EE20/DRSP/L-5-MTHF Ca for Period 2; YAZ for Period 3. Metafolin: single oral administration of 1 coated SHT04532C tablet, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[MTHF-Ca\]) / 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 \[MTHF-Ca\]) / YAZ: single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP).
|
|---|---|---|---|---|---|---|
|
Period 1
STARTED
|
7
|
8
|
7
|
7
|
9
|
6
|
|
Period 1
COMPLETED
|
7
|
8
|
7
|
7
|
9
|
6
|
|
Period 1
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Period 2
STARTED
|
7
|
8
|
7
|
7
|
9
|
6
|
|
Period 2
COMPLETED
|
7
|
8
|
7
|
7
|
8
|
6
|
|
Period 2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
1
|
0
|
|
Period 3
STARTED
|
7
|
8
|
7
|
7
|
8
|
6
|
|
Period 3
COMPLETED
|
6
|
7
|
7
|
7
|
7
|
6
|
|
Period 3
NOT COMPLETED
|
1
|
1
|
0
|
0
|
1
|
0
|
Reasons for withdrawal
| Measure |
Treatment Sequence A: YAZ, EE20/DRSP/L-5-MTHF Ca, Metafolin
YAZ for Period 1; EE20/DRSP/L-5-MTHF Ca for Period 2; Metafolin for Period 3. YAZ: single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP) / 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 \[MTHF-Ca\]) / Metafolin: single oral administration of 1 coated SHT04532C tablet, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[MTHF-Ca\]).
|
Treatment Sequence B: YAZ, Metafolin, EE20/DRSP/L-5-MTHF Ca
YAZ for Period 1; Metafolin for Period 2; EE20/DRSP/L-5-MTHF Ca for Period 3. YAZ: single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP) / Metafolin: single oral administration of 1 coated SHT04532C tablet, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[MTHF-Ca\]) / 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 \[MTHF-Ca\]).
|
Treatment Sequence C: EE20/DRSP/L-5-MTHF Ca, YAZ, Metafolin
EE20/DRSP/L-5-MTHF Ca for Period 1; YAZ for Period 2; Metafolin for Period 3. 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 \[MTHF-Ca\]) / YAZ: single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP) / Metafolin: single oral administration of 1 coated SHT04532C tablet, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[MTHF-Ca\]).
|
Treatment Sequence D: EE20/DRSP/L-5-MTHF Ca, Metafolin, YAZ
EE20/DRSP/L-5-MTHF Ca for Period 1; Metafolin for Period 2; YAZ for Period 3. 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 \[MTHF-Ca\]) / Metafolin: single oral administration of 1 coated SHT04532C tablet, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[MTHF-Ca\]) / YAZ: single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP).
|
Treatment Sequence E: Metafolin, YAZ, EE20/DRSP/L-5-MTHF Ca
Metafolin for Period 1; YAZ for Period 2; EE20/DRSP/L-5-MTHF Ca for Period 3. Metafolin: single oral administration of 1 coated SHT04532C tablet, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[MTHF-Ca\]) / YAZ: single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP) / 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 \[MTHF-Ca\]).
|
Treatment Sequence F: Metafolin, EE20/DRSP/L-5-MTHF Ca, YAZ
Metafolin for Period 1; EE20/DRSP/L-5-MTHF Ca for Period 2; YAZ for Period 3. Metafolin: single oral administration of 1 coated SHT04532C tablet, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[MTHF-Ca\]) / 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 \[MTHF-Ca\]) / YAZ: single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP).
|
|---|---|---|---|---|---|---|
|
Period 2
Withdrawal by Subject
|
0
|
0
|
0
|
0
|
1
|
0
|
|
Period 3
Pregnancy
|
1
|
0
|
0
|
0
|
0
|
0
|
|
Period 3
difficulty with blood sampling
|
0
|
1
|
0
|
0
|
0
|
0
|
|
Period 3
non-compliance
|
0
|
0
|
0
|
0
|
1
|
0
|
Baseline Characteristics
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)
Baseline characteristics by cohort
| Measure |
Entire Study Population
n=44 Participants
Includes all participants treated
|
|---|---|
|
Age Continuous
|
26.3 Years
STANDARD_DEVIATION 6.33 • n=5 Participants
|
|
Sex: Female, Male
Female
|
44 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: up to 96 hours after administrationPopulation: Note that not all samples were evaluable for each outcome measure. Therefore the number of participants analyzed not necessarily matches the number of completers.
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
Outcome measures
| Measure |
EE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300)
n=39 Participants
single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP)
|
EE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca)
n=39 Participants
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 \[L-5-MTHF Ca\])
|
|---|---|---|
|
Mean Maximum Concentration (Cmax) of EE Incl. Bioequivalence (BE) Evaluation
|
39.6 pg/mL
Interval 35.7 to 44.0
|
41.9 pg/mL
Interval 37.6 to 46.7
|
PRIMARY outcome
Timeframe: up to 96 hours after administrationPopulation: Note that not all samples were evaluable for each outcome measure. Therefore the number of participants analyzed not necessarily matches the number of completers.
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
Outcome measures
| Measure |
EE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300)
n=39 Participants
single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP)
|
EE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca)
n=39 Participants
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 \[L-5-MTHF Ca\])
|
|---|---|---|
|
Mean Area Under the Concentration-time Curve From Administration to the Last Measurement [AUC(0-tlast)] of EE Incl. Bioequivalence (BE) Evaluation
|
358 pg·h/mL
Interval 320.0 to 400.0
|
370 pg·h/mL
Interval 332.0 to 412.0
|
PRIMARY outcome
Timeframe: up to 168 hours after administrationPopulation: Note that not all samples were evaluable for each outcome measure. Therefore the number of participants analyzed not necessarily matches the number of completers.
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
Outcome measures
| Measure |
EE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300)
n=35 Participants
single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP)
|
EE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca)
n=36 Participants
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 \[L-5-MTHF Ca\])
|
|---|---|---|
|
Mean Maximum Concentration (Cmax) of DRSP Incl. Bioequivalence (BE) Evaluation
|
25.4 ng/mL
Interval 23.3 to 27.7
|
26.7 ng/mL
Interval 24.5 to 29.1
|
PRIMARY outcome
Timeframe: up to 168 hours after administrationPopulation: Note that not all samples were evaluable for each outcome measure. Therefore the number of participants analyzed not necessarily matches the number of completers.
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
Outcome measures
| Measure |
EE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300)
n=35 Participants
single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP)
|
EE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca)
n=36 Participants
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 \[L-5-MTHF Ca\])
|
|---|---|---|
|
Mean Area Under the Concentration-time Curve From Administration to the Last Measurement [AUC(0-tlast)] of DRSP Incl. Bioequivalence (BE) Evaluation
|
386 ng·h/mL
Interval 352.0 to 424.0
|
383 ng·h/mL
Interval 346.0 to 424.0
|
PRIMARY outcome
Timeframe: up to 12 hours after administrationPopulation: Note that not all samples were evaluable for each outcome measure. Therefore the number of participants analyzed not necessarily matches the number of completers.
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.
Outcome measures
| Measure |
EE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300)
n=39 Participants
single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP)
|
EE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca)
n=40 Participants
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 \[L-5-MTHF Ca\])
|
|---|---|---|
|
Mean Maximum Concentration (Cmax) of L-5-methyl-THF (Baseline Corrected) Incl. Bioequivalence (BE) Evaluation
|
44.3 nmol/L
Interval 40.0 to 49.2
|
44.2 nmol/L
Interval 39.1 to 49.9
|
PRIMARY outcome
Timeframe: up to 12 hours after administrationPopulation: Note that not all samples were evaluable for each outcome measure. Therefore the number of participants analyzed not necessarily matches the number of completers.
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.
Outcome measures
| Measure |
EE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300)
n=39 Participants
single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP)
|
EE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca)
n=40 Participants
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 \[L-5-MTHF Ca\])
|
|---|---|---|
|
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
|
214 nmol·h/L
Interval 195.0 to 235.0
|
217 nmol·h/L
Interval 199.0 to 237.0
|
PRIMARY outcome
Timeframe: up to 12 hours after administrationPopulation: Note that not all samples were evaluable for each outcome measure. Therefore the number of participants analyzed not necessarily matches the number of completers.
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.
Outcome measures
| Measure |
EE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300)
n=40 Participants
single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP)
|
EE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca)
n=40 Participants
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 \[L-5-MTHF Ca\])
|
|---|---|---|
|
Mean Maximum Concentration (Cmax) of L-5-methyl-THF (Baseline Uncorrected) Incl. Bioequivalence (BE) Evaluation
|
57.9 nmol/L
Interval 52.6 to 63.6
|
57.7 nmol/L
Interval 51.7 to 64.4
|
PRIMARY outcome
Timeframe: up to 12 hours after administrationPopulation: Note that not all samples were evaluable for each outcome measure. Therefore the number of participants analyzed not necessarily matches the number of completers.
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.
Outcome measures
| Measure |
EE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300)
n=40 Participants
single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP)
|
EE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca)
n=40 Participants
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 \[L-5-MTHF Ca\])
|
|---|---|---|
|
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
|
370 nmol·h/L
Interval 333.0 to 412.0
|
370 nmol·h/L
Interval 334.0 to 411.0
|
SECONDARY outcome
Timeframe: up to 96 hours after administrationPopulation: Note that not all samples were evaluable for each outcome measure. Therefore the number of participants analyzed not necessarily matches the number of completers.
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
Outcome measures
| Measure |
EE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300)
n=39 Participants
single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP)
|
EE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca)
n=39 Participants
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 \[L-5-MTHF Ca\])
|
|---|---|---|
|
Time to Reach Maximum Concentration (Tmax) of EE
|
1.50 hours
Interval 0.5 to 4.0
|
1.52 hours
Interval 1.0 to 4.18
|
SECONDARY outcome
Timeframe: up to 72 hours after administrationPopulation: Note that not all samples were evaluable for each outcome measure. Therefore the number of participants analyzed not necessarily matches the number of completers.
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
Outcome measures
| Measure |
EE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300)
n=34 Participants
single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP)
|
EE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca)
n=36 Participants
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 \[L-5-MTHF Ca\])
|
|---|---|---|
|
Mean Area Under the Concentration-time Curve From Administration up to 72h AUC(0-72h) of DRSP
|
350 ng·h/mL
Interval 328.0 to 373.0
|
344 ng·h/mL
Interval 319.0 to 371.0
|
SECONDARY outcome
Timeframe: up to 168 hours after administrationPopulation: Note that not all samples were evaluable for each outcome measure. Therefore the number of participants analyzed not necessarily matches the number of completers.
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
Outcome measures
| Measure |
EE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300)
n=35 Participants
single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP)
|
EE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca)
n=36 Participants
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 \[L-5-MTHF Ca\])
|
|---|---|---|
|
Time to Reach Maximum Concentration (Tmax) of DRSP
|
2.00 hours
Interval 0.5 to 4.0
|
2.00 hours
Interval 0.5 to 4.1
|
SECONDARY outcome
Timeframe: up to 12 hours after administrationPopulation: Note that not all samples were evaluable for each outcome measure. Therefore the number of participants analyzed not necessarily matches the number of completers.
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
Outcome measures
| Measure |
EE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300)
n=40 Participants
single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP)
|
EE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca)
n=40 Participants
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 \[L-5-MTHF Ca\])
|
|---|---|---|
|
Time to Reach Maximum Concentration (Tmax) of L-5-methyl-THF
|
0.50 hours
Interval 0.0 to 4.0
|
0.50 hours
Interval 0.5 to 2.0
|
Adverse Events
EE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300)
Serious events: 0 serious events
Other events: 37 other events
Deaths: 0 deaths
EE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca)
Serious events: 0 serious events
Other events: 30 other events
Deaths: 0 deaths
L-5-MTHF Ca 0.451 mg (Metafolin)
Serious events: 0 serious events
Other events: 34 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
EE 0.02 mg/DRSP 3 mg (YAZ, BAY86-5300)
n=43 participants at risk
single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP)
|
EE 0.02mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE20/DRSP/L-5-MTHF Ca)
n=41 participants at risk
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 \[MTHF-Ca\])
|
L-5-MTHF Ca 0.451 mg (Metafolin)
n=43 participants at risk
single oral administration of 1 coated SHT04532C tablet, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[MTHF-Ca\])
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.00%
0/43
|
0.00%
0/41
|
2.3%
1/43 • Number of events 1
|
|
Cardiac disorders
Palpitations
|
4.7%
2/43 • Number of events 2
|
0.00%
0/41
|
0.00%
0/43
|
|
Ear and labyrinth disorders
Ear pain
|
0.00%
0/43
|
2.4%
1/41 • Number of events 1
|
0.00%
0/43
|
|
Eye disorders
Conjunctivitis
|
0.00%
0/43
|
2.4%
1/41 • Number of events 1
|
0.00%
0/43
|
|
Eye disorders
Dry eye
|
0.00%
0/43
|
2.4%
1/41 • Number of events 1
|
0.00%
0/43
|
|
Eye disorders
Eyelid irritation
|
0.00%
0/43
|
0.00%
0/41
|
2.3%
1/43 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal discomfort
|
9.3%
4/43 • Number of events 4
|
4.9%
2/41 • Number of events 2
|
2.3%
1/43 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal distension
|
2.3%
1/43 • Number of events 1
|
0.00%
0/41
|
0.00%
0/43
|
|
Gastrointestinal disorders
Abdominal pain
|
4.7%
2/43 • Number of events 2
|
9.8%
4/41 • Number of events 4
|
2.3%
1/43 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain lower
|
0.00%
0/43
|
2.4%
1/41 • Number of events 1
|
0.00%
0/43
|
|
Gastrointestinal disorders
Diarrhoea
|
16.3%
7/43 • Number of events 7
|
12.2%
5/41 • Number of events 5
|
4.7%
2/43 • Number of events 2
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/43
|
2.4%
1/41 • Number of events 1
|
0.00%
0/43
|
|
Gastrointestinal disorders
Eructation
|
2.3%
1/43 • Number of events 1
|
0.00%
0/41
|
0.00%
0/43
|
|
Gastrointestinal disorders
Nausea
|
14.0%
6/43 • Number of events 6
|
26.8%
11/41 • Number of events 11
|
11.6%
5/43 • Number of events 5
|
|
Gastrointestinal disorders
Vomiting
|
2.3%
1/43 • Number of events 1
|
9.8%
4/41 • Number of events 4
|
4.7%
2/43 • Number of events 2
|
|
General disorders
Asthenia
|
9.3%
4/43 • Number of events 4
|
0.00%
0/41
|
0.00%
0/43
|
|
General disorders
Catheter site haematoma
|
0.00%
0/43
|
2.4%
1/41 • Number of events 1
|
0.00%
0/43
|
|
General disorders
Catheter site pain
|
2.3%
1/43 • Number of events 1
|
7.3%
3/41 • Number of events 3
|
0.00%
0/43
|
|
General disorders
Catheter site related reaction
|
4.7%
2/43 • Number of events 3
|
2.4%
1/41 • Number of events 1
|
0.00%
0/43
|
|
General disorders
Chest discomfort
|
0.00%
0/43
|
2.4%
1/41 • Number of events 3
|
0.00%
0/43
|
|
General disorders
Discomfort
|
2.3%
1/43 • Number of events 1
|
0.00%
0/41
|
2.3%
1/43 • Number of events 1
|
|
General disorders
Fatigue
|
11.6%
5/43 • Number of events 6
|
12.2%
5/41 • Number of events 6
|
4.7%
2/43 • Number of events 2
|
|
General disorders
Feeling cold
|
2.3%
1/43 • Number of events 1
|
0.00%
0/41
|
0.00%
0/43
|
|
General disorders
Influenza like illness
|
2.3%
1/43 • Number of events 1
|
0.00%
0/41
|
0.00%
0/43
|
|
General disorders
Orthostatic intolerance
|
2.3%
1/43 • Number of events 1
|
0.00%
0/41
|
0.00%
0/43
|
|
General disorders
Peripheral coldness
|
4.7%
2/43 • Number of events 2
|
0.00%
0/41
|
0.00%
0/43
|
|
General disorders
Puncture site pain
|
2.3%
1/43 • Number of events 1
|
0.00%
0/41
|
0.00%
0/43
|
|
General disorders
Thirst
|
2.3%
1/43 • Number of events 1
|
0.00%
0/41
|
0.00%
0/43
|
|
General disorders
Vessel puncture site pain
|
2.3%
1/43 • Number of events 1
|
0.00%
0/41
|
0.00%
0/43
|
|
Eye disorders
Blepharospasm
|
2.3%
1/43 • Number of events 1
|
0.00%
0/41
|
0.00%
0/43
|
|
Immune system disorders
Seasonal allergy
|
2.3%
1/43 • Number of events 1
|
0.00%
0/41
|
2.3%
1/43 • Number of events 1
|
|
Infections and infestations
Acarodermatitis
|
0.00%
0/43
|
0.00%
0/41
|
2.3%
1/43 • Number of events 1
|
|
Infections and infestations
Influenza
|
2.3%
1/43 • Number of events 1
|
4.9%
2/41 • Number of events 2
|
2.3%
1/43 • Number of events 1
|
|
Infections and infestations
Nasopharyngitis
|
4.7%
2/43 • Number of events 2
|
2.4%
1/41 • Number of events 1
|
7.0%
3/43 • Number of events 3
|
|
Infections and infestations
Rhinitis
|
0.00%
0/43
|
2.4%
1/41 • Number of events 1
|
0.00%
0/43
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/43
|
0.00%
0/41
|
2.3%
1/43 • Number of events 1
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/43
|
2.4%
1/41 • Number of events 1
|
0.00%
0/43
|
|
Injury, poisoning and procedural complications
Periorbital haematoma
|
0.00%
0/43
|
2.4%
1/41 • Number of events 1
|
0.00%
0/43
|
|
Injury, poisoning and procedural complications
Scratch
|
2.3%
1/43 • Number of events 1
|
0.00%
0/41
|
0.00%
0/43
|
|
Investigations
Serum ferritin decreased
|
16.3%
7/43 • Number of events 7
|
14.6%
6/41 • Number of events 6
|
18.6%
8/43 • Number of events 8
|
|
Investigations
Weight increased
|
2.3%
1/43 • Number of events 1
|
0.00%
0/41
|
0.00%
0/43
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
4.7%
2/43 • Number of events 2
|
0.00%
0/41
|
0.00%
0/43
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
2.3%
1/43 • Number of events 1
|
0.00%
0/41
|
0.00%
0/43
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal discomfort
|
2.3%
1/43 • Number of events 1
|
0.00%
0/41
|
0.00%
0/43
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/43
|
2.4%
1/41 • Number of events 1
|
2.3%
1/43 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
2.3%
1/43 • Number of events 1
|
0.00%
0/41
|
0.00%
0/43
|
|
Nervous system disorders
Dizziness
|
4.7%
2/43 • Number of events 4
|
7.3%
3/41 • Number of events 3
|
2.3%
1/43 • Number of events 1
|
|
Nervous system disorders
Headache
|
34.9%
15/43 • Number of events 17
|
22.0%
9/41 • Number of events 11
|
25.6%
11/43 • Number of events 13
|
|
Nervous system disorders
Hypoaesthesia
|
2.3%
1/43 • Number of events 2
|
2.4%
1/41 • Number of events 1
|
0.00%
0/43
|
|
Nervous system disorders
Syncope vasovagal
|
16.3%
7/43 • Number of events 8
|
7.3%
3/41 • Number of events 4
|
4.7%
2/43 • Number of events 2
|
|
Nervous system disorders
Tremor
|
4.7%
2/43 • Number of events 2
|
0.00%
0/41
|
0.00%
0/43
|
|
Psychiatric disorders
Anxiety
|
2.3%
1/43 • Number of events 1
|
0.00%
0/41
|
0.00%
0/43
|
|
Psychiatric disorders
Emotional disorder
|
2.3%
1/43 • Number of events 1
|
0.00%
0/41
|
0.00%
0/43
|
|
Psychiatric disorders
Restlessness
|
0.00%
0/43
|
2.4%
1/41 • Number of events 1
|
0.00%
0/43
|
|
Psychiatric disorders
Sleep disorder
|
0.00%
0/43
|
2.4%
1/41 • Number of events 1
|
0.00%
0/43
|
|
Reproductive system and breast disorders
Dysmenorrhoea
|
0.00%
0/43
|
4.9%
2/41 • Number of events 2
|
2.3%
1/43 • Number of events 1
|
|
Reproductive system and breast disorders
Metrorrhagia
|
23.3%
10/43 • Number of events 10
|
22.0%
9/41 • Number of events 9
|
0.00%
0/43
|
|
Respiratory, thoracic and mediastinal disorders
Apnoea
|
2.3%
1/43 • Number of events 1
|
0.00%
0/41
|
0.00%
0/43
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.3%
1/43 • Number of events 1
|
0.00%
0/41
|
0.00%
0/43
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
0.00%
0/43
|
2.4%
1/41 • Number of events 1
|
0.00%
0/43
|
|
Skin and subcutaneous tissue disorders
Acne
|
0.00%
0/43
|
2.4%
1/41 • Number of events 1
|
2.3%
1/43 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Blister
|
0.00%
0/43
|
0.00%
0/41
|
2.3%
1/43 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Dermal cyst
|
2.3%
1/43 • Number of events 1
|
0.00%
0/41
|
0.00%
0/43
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
0.00%
0/43
|
0.00%
0/41
|
2.3%
1/43 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/43
|
2.4%
1/41 • Number of events 1
|
0.00%
0/43
|
|
Surgical and medical procedures
Dental treatment
|
2.3%
1/43 • Number of events 1
|
0.00%
0/41
|
0.00%
0/43
|
|
Vascular disorders
Flushing
|
2.3%
1/43 • Number of events 1
|
0.00%
0/41
|
0.00%
0/43
|
|
Vascular disorders
Haematoma
|
2.3%
1/43 • Number of events 1
|
0.00%
0/41
|
0.00%
0/43
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee PI (principal investigator) of CRO (contract research organization) will refrain from publishing any data or information generated or derived as a result of the performance of the Services.
- Publication restrictions are in place
Restriction type: OTHER