Trial Outcomes & Findings for Investigation of Bioequivalence of Ethinylestradiol (EE) and Drospirenone (DRSP) in Two Different Tablet Formulations: Yasmin and Yasmin + Levomefolate Calcium (Metafolin) & L-5-MTHF in Two Different Tablet Formulations: Levomefolate Calcium (Metafolin) and Yasmin + Levomefolate Calcium (Metafolin) (NCT NCT01253174)
NCT ID: NCT01253174
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
48 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 16 August 2006 to 4 July 2007 at one center in Germany.
147 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 48 volunteers were randomized at one center.
Participant milestones
| Measure |
Treatment Sequence A: Yasmin, EE30/DRSP/L-5-MTHF Ca, Metafolin
Yasmin for Period 1; EE30/DRSP/L-5-MTHF Ca for Period 2; Metafolin for Period 3. Yasmin: single oral administration of 1 film-coated SHT470FA tablet (Yasmin with ethinylestradiol (EE) as free steroid), containing 0.030 mg EE + 3 mg drospirenone (DRSP) / EE30/DRSP/L-5-MTHF Ca: single oral administration of 1 film-coated SHT04532A tablet (with ethinylestradiol (EE) as clathtrate), containing 0.030 mg EE + 3 mg drospirenone (DRSP) + 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[L-5-MTHF Ca\]) / Metafolin: single oral administration of 1 coated tablet SHT04532C, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[L-5-MTHF Ca\]).
|
Treatment Sequence B: Yasmin, Metafolin, EE30/DRSP/L-5-MTHF Ca
Yasmin for Period 1; Metafolin for Period 2; EE30/DRSP/L-5-MTHF Ca for Period 3. Yasmin: single oral administration of 1 film-coated SHT470FA tablet (Yasmin with ethinylestradiol (EE) as free steroid), containing 0.030 mg EE + 3 mg drospirenone (DRSP) / Metafolin: single oral administration of 1 coated tablet SHT04532C, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[L-5-MTHF Ca\]) / EE30/DRSP/L-5-MTHF Ca: single oral administration of 1 film-coated SHT04532A tablet (with ethinylestradiol (EE) as clathtrate), containing 0.030 mg EE + 3 mg drospirenone (DRSP) + 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[L-5-MTHF Ca\]).
|
Treatment Sequence C: EE30/DRSP/L-5-MTHF Ca, Yasmin, Metafolin
EE30/DRSP/L-5-MTHF Ca for Period 1; Yasmin for Period 2; Metafolin for Period 3. EE30/DRSP/L-5-MTHF Ca: single oral administration of 1 film-coated SHT04532A tablet (with ethinylestradiol (EE) as clathtrate), containing 0.030 mg EE + 3 mg drospirenone (DRSP) + 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[L-5-MTHF Ca\]) / Yasmin: single oral administration of 1 film-coated SHT470FA tablet (Yasmin with ethinylestradiol (EE) as free steroid), containing 0.030 mg EE + 3 mg drospirenone (DRSP) / Metafolin: single oral administration of 1 coated tablet SHT04532C, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[L-5-MTHF Ca\]).
|
Treatment Sequence D: EE30/DRSP/L-5-MTHF Ca, Metafolin, Yasmin
EE30/DRSP/L-5-MTHF Ca for Period 1; Metafolin for Period 2; Yasmin for Period 3. EE30/DRSP/L-5-MTHF Ca: single oral administration of 1 film-coated SHT04532A tablet (with ethinylestradiol (EE) as clathtrate), containing 0.030 mg EE + 3 mg drospirenone (DRSP) + 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[L-5-MTHF Ca\]) / Metafolin: single oral administration of 1 coated tablet SHT04532C, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[L-5-MTHF Ca\]) / Yasmin: single oral administration of 1 film-coated SHT470FA tablet (Yasmin with ethinylestradiol (EE) as free steroid), containing 0.030 mg EE + 3 mg drospirenone (DRSP).
|
Treatment Sequence E: Metafolin, Yasmin, EE30/DRSP/L-5-MTHF Ca
Metafolin for Period 1; Yasmin for Period 2; EE30/DRSP/L-5-MTHF Ca for Period 3. Metafolin: single oral administration of 1 coated tablet SHT04532C, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[L-5-MTHF Ca\]) / Yasmin: single oral administration of 1 film-coated SHT470FA tablet (Yasmin with ethinylestradiol (EE) as free steroid), containing 0.030 mg EE + 3 mg drospirenone (DRSP) / EE30/DRSP/L-5-MTHF Ca: single oral administration of 1 film-coated SHT04532A tablet (with ethinylestradiol (EE) as clathtrate), containing 0.030 mg EE + 3 mg drospirenone (DRSP) + 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[L-5-MTHF Ca\]).
|
Treatment Sequence F: Metafolin, EE30/DRSP/L-5-MTHF Ca, Yasmin
Metafolin for Period 1; EE30/DRSP/L-5-MTHF Ca for Period 2; Yasmin for Period 3. Metafolin: single oral administration of 1 coated tablet SHT04532C, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[L-5-MTHF Ca\]) / EE30/DRSP/L-5-MTHF Ca: single oral administration of 1 film-coated SHT04532A tablet (with ethinylestradiol (EE) as clathtrate), containing 0.030 mg EE + 3 mg drospirenone (DRSP) + 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[L-5-MTHF Ca\]) / Yasmin: single oral administration of 1 film-coated SHT470FA tablet (Yasmin with ethinylestradiol (EE) as free steroid), containing 0.030 mg EE + 3 mg drospirenone (DRSP).
|
|---|---|---|---|---|---|---|
|
Period 1
STARTED
|
6
|
10
|
9
|
7
|
9
|
7
|
|
Period 1
COMPLETED
|
6
|
9
|
8
|
7
|
8
|
7
|
|
Period 1
NOT COMPLETED
|
0
|
1
|
1
|
0
|
1
|
0
|
|
Period 2
STARTED
|
6
|
9
|
8
|
7
|
8
|
7
|
|
Period 2
COMPLETED
|
6
|
9
|
7
|
7
|
8
|
7
|
|
Period 2
NOT COMPLETED
|
0
|
0
|
1
|
0
|
0
|
0
|
|
Period 3
STARTED
|
6
|
9
|
7
|
7
|
8
|
7
|
|
Period 3
COMPLETED
|
6
|
8
|
6
|
7
|
7
|
7
|
|
Period 3
NOT COMPLETED
|
0
|
1
|
1
|
0
|
1
|
0
|
Reasons for withdrawal
| Measure |
Treatment Sequence A: Yasmin, EE30/DRSP/L-5-MTHF Ca, Metafolin
Yasmin for Period 1; EE30/DRSP/L-5-MTHF Ca for Period 2; Metafolin for Period 3. Yasmin: single oral administration of 1 film-coated SHT470FA tablet (Yasmin with ethinylestradiol (EE) as free steroid), containing 0.030 mg EE + 3 mg drospirenone (DRSP) / EE30/DRSP/L-5-MTHF Ca: single oral administration of 1 film-coated SHT04532A tablet (with ethinylestradiol (EE) as clathtrate), containing 0.030 mg EE + 3 mg drospirenone (DRSP) + 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[L-5-MTHF Ca\]) / Metafolin: single oral administration of 1 coated tablet SHT04532C, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[L-5-MTHF Ca\]).
|
Treatment Sequence B: Yasmin, Metafolin, EE30/DRSP/L-5-MTHF Ca
Yasmin for Period 1; Metafolin for Period 2; EE30/DRSP/L-5-MTHF Ca for Period 3. Yasmin: single oral administration of 1 film-coated SHT470FA tablet (Yasmin with ethinylestradiol (EE) as free steroid), containing 0.030 mg EE + 3 mg drospirenone (DRSP) / Metafolin: single oral administration of 1 coated tablet SHT04532C, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[L-5-MTHF Ca\]) / EE30/DRSP/L-5-MTHF Ca: single oral administration of 1 film-coated SHT04532A tablet (with ethinylestradiol (EE) as clathtrate), containing 0.030 mg EE + 3 mg drospirenone (DRSP) + 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[L-5-MTHF Ca\]).
|
Treatment Sequence C: EE30/DRSP/L-5-MTHF Ca, Yasmin, Metafolin
EE30/DRSP/L-5-MTHF Ca for Period 1; Yasmin for Period 2; Metafolin for Period 3. EE30/DRSP/L-5-MTHF Ca: single oral administration of 1 film-coated SHT04532A tablet (with ethinylestradiol (EE) as clathtrate), containing 0.030 mg EE + 3 mg drospirenone (DRSP) + 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[L-5-MTHF Ca\]) / Yasmin: single oral administration of 1 film-coated SHT470FA tablet (Yasmin with ethinylestradiol (EE) as free steroid), containing 0.030 mg EE + 3 mg drospirenone (DRSP) / Metafolin: single oral administration of 1 coated tablet SHT04532C, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[L-5-MTHF Ca\]).
|
Treatment Sequence D: EE30/DRSP/L-5-MTHF Ca, Metafolin, Yasmin
EE30/DRSP/L-5-MTHF Ca for Period 1; Metafolin for Period 2; Yasmin for Period 3. EE30/DRSP/L-5-MTHF Ca: single oral administration of 1 film-coated SHT04532A tablet (with ethinylestradiol (EE) as clathtrate), containing 0.030 mg EE + 3 mg drospirenone (DRSP) + 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[L-5-MTHF Ca\]) / Metafolin: single oral administration of 1 coated tablet SHT04532C, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[L-5-MTHF Ca\]) / Yasmin: single oral administration of 1 film-coated SHT470FA tablet (Yasmin with ethinylestradiol (EE) as free steroid), containing 0.030 mg EE + 3 mg drospirenone (DRSP).
|
Treatment Sequence E: Metafolin, Yasmin, EE30/DRSP/L-5-MTHF Ca
Metafolin for Period 1; Yasmin for Period 2; EE30/DRSP/L-5-MTHF Ca for Period 3. Metafolin: single oral administration of 1 coated tablet SHT04532C, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[L-5-MTHF Ca\]) / Yasmin: single oral administration of 1 film-coated SHT470FA tablet (Yasmin with ethinylestradiol (EE) as free steroid), containing 0.030 mg EE + 3 mg drospirenone (DRSP) / EE30/DRSP/L-5-MTHF Ca: single oral administration of 1 film-coated SHT04532A tablet (with ethinylestradiol (EE) as clathtrate), containing 0.030 mg EE + 3 mg drospirenone (DRSP) + 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[L-5-MTHF Ca\]).
|
Treatment Sequence F: Metafolin, EE30/DRSP/L-5-MTHF Ca, Yasmin
Metafolin for Period 1; EE30/DRSP/L-5-MTHF Ca for Period 2; Yasmin for Period 3. Metafolin: single oral administration of 1 coated tablet SHT04532C, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[L-5-MTHF Ca\]) / EE30/DRSP/L-5-MTHF Ca: single oral administration of 1 film-coated SHT04532A tablet (with ethinylestradiol (EE) as clathtrate), containing 0.030 mg EE + 3 mg drospirenone (DRSP) + 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[L-5-MTHF Ca\]) / Yasmin: single oral administration of 1 film-coated SHT470FA tablet (Yasmin with ethinylestradiol (EE) as free steroid), containing 0.030 mg EE + 3 mg drospirenone (DRSP).
|
|---|---|---|---|---|---|---|
|
Period 1
Randomized but not treated
|
0
|
1
|
1
|
0
|
1
|
0
|
|
Period 2
Adverse Event
|
0
|
0
|
1
|
0
|
0
|
0
|
|
Period 3
Withdrawal by Subject
|
0
|
1
|
0
|
0
|
1
|
0
|
|
Period 3
Pregnancy
|
0
|
0
|
1
|
0
|
0
|
0
|
Baseline Characteristics
Investigation of Bioequivalence of Ethinylestradiol (EE) and Drospirenone (DRSP) in Two Different Tablet Formulations: Yasmin and Yasmin + Levomefolate Calcium (Metafolin) & L-5-MTHF in Two Different Tablet Formulations: Levomefolate Calcium (Metafolin) and Yasmin + Levomefolate Calcium (Metafolin)
Baseline characteristics by cohort
| Measure |
Entire Study Population
n=45 Participants
Includes all participants treated
|
|---|---|
|
Age Continuous
|
29.7 years
STANDARD_DEVIATION 4.62 • n=5 Participants
|
|
Sex: Female, Male
Female
|
45 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 0.03 mg/DRSP 3 mg (Yasmin, BAY86-5131)
n=42 Participants
single oral administration of 1 film-coated SHT470FA tablet (Yasmin with ethinylestradiol (EE) as free steroid), containing 0.030 mg EE + 3 mg drospirenone (DRSP)
|
EE 0.03mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE30/DRSP/L-5-MTHF Ca)
n=42 Participants
single oral administration of 1 film-coated SHT04532A tablet (with ethinylestradiol (EE) as clathtrate), containing 0.030 mg 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
|
58.5 pg/mL
Interval 53.1 to 64.4
|
61.6 pg/mL
Interval 56.6 to 67.0
|
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 0.03 mg/DRSP 3 mg (Yasmin, BAY86-5131)
n=42 Participants
single oral administration of 1 film-coated SHT470FA tablet (Yasmin with ethinylestradiol (EE) as free steroid), containing 0.030 mg EE + 3 mg drospirenone (DRSP)
|
EE 0.03mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE30/DRSP/L-5-MTHF Ca)
n=42 Participants
single oral administration of 1 film-coated SHT04532A tablet (with ethinylestradiol (EE) as clathtrate), containing 0.030 mg 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
|
573 pg∙h/mL
Interval 521.0 to 632.0
|
595 pg∙h/mL
Interval 544.0 to 651.0
|
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 0.03 mg/DRSP 3 mg (Yasmin, BAY86-5131)
n=40 Participants
single oral administration of 1 film-coated SHT470FA tablet (Yasmin with ethinylestradiol (EE) as free steroid), containing 0.030 mg EE + 3 mg drospirenone (DRSP)
|
EE 0.03mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE30/DRSP/L-5-MTHF Ca)
n=40 Participants
single oral administration of 1 film-coated SHT04532A tablet (with ethinylestradiol (EE) as clathtrate), containing 0.030 mg 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
|
26.3 ng/mL
Interval 23.9 to 28.9
|
27.2 ng/mL
Interval 25.3 to 29.2
|
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 0.03 mg/DRSP 3 mg (Yasmin, BAY86-5131)
n=40 Participants
single oral administration of 1 film-coated SHT470FA tablet (Yasmin with ethinylestradiol (EE) as free steroid), containing 0.030 mg EE + 3 mg drospirenone (DRSP)
|
EE 0.03mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE30/DRSP/L-5-MTHF Ca)
n=40 Participants
single oral administration of 1 film-coated SHT04532A tablet (with ethinylestradiol (EE) as clathtrate), containing 0.030 mg EE + 3 mg drospirenone (DRSP) + 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[L-5-MTHF Ca\])
|
|---|---|---|
|
Mean Area Under the Concentration-time Curve (AUC) of DRSP Incl. Bioequivalence (BE) Evaluation
|
433 ng∙h/mL
Interval 397.0 to 473.0
|
447 ng∙h/mL
Interval 417.0 to 479.0
|
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 0.03 mg/DRSP 3 mg (Yasmin, BAY86-5131)
n=41 Participants
single oral administration of 1 film-coated SHT470FA tablet (Yasmin with ethinylestradiol (EE) as free steroid), containing 0.030 mg EE + 3 mg drospirenone (DRSP)
|
EE 0.03mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE30/DRSP/L-5-MTHF Ca)
n=43 Participants
single oral administration of 1 film-coated SHT04532A tablet (with ethinylestradiol (EE) as clathtrate), containing 0.030 mg 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
|
51.7 nmol/L
Interval 47.1 to 56.9
|
48.7 nmol/L
Interval 44.5 to 53.4
|
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 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 0.03 mg/DRSP 3 mg (Yasmin, BAY86-5131)
n=41 Participants
single oral administration of 1 film-coated SHT470FA tablet (Yasmin with ethinylestradiol (EE) as free steroid), containing 0.030 mg EE + 3 mg drospirenone (DRSP)
|
EE 0.03mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE30/DRSP/L-5-MTHF Ca)
n=43 Participants
single oral administration of 1 film-coated SHT04532A tablet (with ethinylestradiol (EE) as clathtrate), containing 0.030 mg 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
|
236 nmol∙h/L
Interval 218.0 to 256.0
|
239 nmol∙h/L
Interval 221.0 to 259.0
|
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 0.03 mg/DRSP 3 mg (Yasmin, BAY86-5131)
n=41 Participants
single oral administration of 1 film-coated SHT470FA tablet (Yasmin with ethinylestradiol (EE) as free steroid), containing 0.030 mg EE + 3 mg drospirenone (DRSP)
|
EE 0.03mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE30/DRSP/L-5-MTHF Ca)
n=43 Participants
single oral administration of 1 film-coated SHT04532A tablet (with ethinylestradiol (EE) as clathtrate), containing 0.030 mg 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
|
65.2 nmol/L
Interval 59.3 to 71.6
|
61.8 nmol/L
Interval 56.6 to 67.5
|
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 0.03 mg/DRSP 3 mg (Yasmin, BAY86-5131)
n=41 Participants
single oral administration of 1 film-coated SHT470FA tablet (Yasmin with ethinylestradiol (EE) as free steroid), containing 0.030 mg EE + 3 mg drospirenone (DRSP)
|
EE 0.03mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE30/DRSP/L-5-MTHF Ca)
n=43 Participants
single oral administration of 1 film-coated SHT04532A tablet (with ethinylestradiol (EE) as clathtrate), containing 0.030 mg 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
|
393 nmol∙h/L
Interval 356.0 to 435.0
|
390 nmol∙h/L
Interval 353.0 to 431.0
|
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 0.03 mg/DRSP 3 mg (Yasmin, BAY86-5131)
n=42 Participants
single oral administration of 1 film-coated SHT470FA tablet (Yasmin with ethinylestradiol (EE) as free steroid), containing 0.030 mg EE + 3 mg drospirenone (DRSP)
|
EE 0.03mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE30/DRSP/L-5-MTHF Ca)
n=42 Participants
single oral administration of 1 film-coated SHT04532A tablet (with ethinylestradiol (EE) as clathtrate), containing 0.030 mg 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
|
2.00 hour
Interval 0.5 to 4.0
|
2.00 hour
Interval 1.0 to 4.0
|
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 0.03 mg/DRSP 3 mg (Yasmin, BAY86-5131)
n=40 Participants
single oral administration of 1 film-coated SHT470FA tablet (Yasmin with ethinylestradiol (EE) as free steroid), containing 0.030 mg EE + 3 mg drospirenone (DRSP)
|
EE 0.03mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE30/DRSP/L-5-MTHF Ca)
n=40 Participants
single oral administration of 1 film-coated SHT04532A tablet (with ethinylestradiol (EE) as clathtrate), containing 0.030 mg 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
|
352 ng∙h/mL
Interval 323.0 to 383.0
|
366 ng∙h/mL
Interval 346.0 to 388.0
|
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 0.03 mg/DRSP 3 mg (Yasmin, BAY86-5131)
n=40 Participants
single oral administration of 1 film-coated SHT470FA tablet (Yasmin with ethinylestradiol (EE) as free steroid), containing 0.030 mg EE + 3 mg drospirenone (DRSP)
|
EE 0.03mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE30/DRSP/L-5-MTHF Ca)
n=40 Participants
single oral administration of 1 film-coated SHT04532A tablet (with ethinylestradiol (EE) as clathtrate), containing 0.030 mg 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
|
1.50 hour
Interval 1.0 to 3.0
|
1.50 hour
Interval 0.5 to 3.0
|
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 0.03 mg/DRSP 3 mg (Yasmin, BAY86-5131)
n=41 Participants
single oral administration of 1 film-coated SHT470FA tablet (Yasmin with ethinylestradiol (EE) as free steroid), containing 0.030 mg EE + 3 mg drospirenone (DRSP)
|
EE 0.03mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE30/DRSP/L-5-MTHF Ca)
n=43 Participants
single oral administration of 1 film-coated SHT04532A tablet (with ethinylestradiol (EE) as clathtrate), containing 0.030 mg 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 hour
Interval 0.5 to 1.5
|
0.50 hour
Interval 0.5 to 1.5
|
Adverse Events
EE 0.03 mg/DRSP 3 mg (Yasmin, BAY86-5131)
Serious events: 0 serious events
Other events: 27 other events
Deaths: 0 deaths
EE 0.03mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE30/DRSP/L-5-MTHF Ca)
Serious events: 0 serious events
Other events: 31 other events
Deaths: 0 deaths
L-5-MTHF Ca 0.451mg (Metafolin)
Serious events: 0 serious events
Other events: 16 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
EE 0.03 mg/DRSP 3 mg (Yasmin, BAY86-5131)
n=44 participants at risk
single oral administration of 1 film-coated SHT470FA tablet (Yasmin with ethinylestradiol (EE) as free steroid), containing 0.030 mg EE + 3 mg drospirenone (DRSP)
|
EE 0.03mg/DRSP 3mg/L-5-MTHF Ca 0.451mg (EE30/DRSP/L-5-MTHF Ca)
n=43 participants at risk
single oral administration of 1 film-coated SHT04532A tablet (with ethinylestradiol (EE) as clathtrate), containing 0.030 mg EE + 3 mg drospirenone (DRSP) + 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[L-5-MTHF Ca\])
|
L-5-MTHF Ca 0.451mg (Metafolin)
n=43 participants at risk
single oral administration of 1 coated tablet SHT04532C, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium \[L-5-MTHF Ca\])
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
2.3%
1/44 • Number of events 1
|
0.00%
0/43
|
0.00%
0/43
|
|
Gastrointestinal disorders
Abdominal discomfort
|
2.3%
1/44 • Number of events 1
|
0.00%
0/43
|
0.00%
0/43
|
|
Gastrointestinal disorders
Abdominal pain
|
4.5%
2/44 • Number of events 2
|
0.00%
0/43
|
0.00%
0/43
|
|
Gastrointestinal disorders
Abdominal pain upper
|
2.3%
1/44 • Number of events 1
|
0.00%
0/43
|
0.00%
0/43
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/44
|
2.3%
1/43 • Number of events 1
|
0.00%
0/43
|
|
Gastrointestinal disorders
Nausea
|
22.7%
10/44 • Number of events 10
|
14.0%
6/43 • Number of events 6
|
0.00%
0/43
|
|
Gastrointestinal disorders
Vomiting
|
4.5%
2/44 • Number of events 2
|
20.9%
9/43 • Number of events 9
|
4.7%
2/43 • Number of events 2
|
|
General disorders
Vessel puncture site haematoma
|
2.3%
1/44 • Number of events 1
|
0.00%
0/43
|
0.00%
0/43
|
|
General disorders
Vessel puncture site pain
|
0.00%
0/44
|
0.00%
0/43
|
2.3%
1/43 • Number of events 2
|
|
Infections and infestations
Bronchitis
|
2.3%
1/44 • Number of events 1
|
0.00%
0/43
|
0.00%
0/43
|
|
Infections and infestations
Nasopharyngitis
|
2.3%
1/44 • Number of events 1
|
2.3%
1/43 • Number of events 1
|
0.00%
0/43
|
|
Infections and infestations
Oral herpes
|
0.00%
0/44
|
2.3%
1/43 • Number of events 1
|
0.00%
0/43
|
|
Investigations
Serum ferritin decreased
|
20.5%
9/44 • Number of events 9
|
27.9%
12/43 • Number of events 12
|
16.3%
7/43 • Number of events 7
|
|
Investigations
Weight increased
|
0.00%
0/44
|
2.3%
1/43 • Number of events 1
|
0.00%
0/43
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
2.3%
1/44 • Number of events 1
|
0.00%
0/43
|
0.00%
0/43
|
|
Nervous system disorders
Dizziness
|
4.5%
2/44 • Number of events 2
|
4.7%
2/43 • Number of events 2
|
0.00%
0/43
|
|
Nervous system disorders
Headache
|
15.9%
7/44 • Number of events 8
|
9.3%
4/43 • Number of events 4
|
14.0%
6/43 • Number of events 7
|
|
Nervous system disorders
Syncope vasovagal
|
2.3%
1/44 • Number of events 2
|
2.3%
1/43 • Number of events 1
|
0.00%
0/43
|
|
Psychiatric disorders
Mood swings
|
2.3%
1/44 • Number of events 1
|
0.00%
0/43
|
0.00%
0/43
|
|
Renal and urinary disorders
Enuresis
|
2.3%
1/44 • Number of events 1
|
0.00%
0/43
|
0.00%
0/43
|
|
Reproductive system and breast disorders
Breast discomfort
|
0.00%
0/44
|
4.7%
2/43 • Number of events 2
|
0.00%
0/43
|
|
Reproductive system and breast disorders
Metrorrhagia
|
6.8%
3/44 • Number of events 3
|
16.3%
7/43 • Number of events 8
|
0.00%
0/43
|
|
Skin and subcutaneous tissue disorders
Dermatitis allergic
|
0.00%
0/44
|
2.3%
1/43 • Number of events 1
|
0.00%
0/43
|
|
Skin and subcutaneous tissue disorders
Pityriasis rosea
|
0.00%
0/44
|
0.00%
0/43
|
2.3%
1/43 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Urticaria generalised
|
2.3%
1/44 • Number of events 1
|
0.00%
0/43
|
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