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)
Sponsor
Bayer (Industry)
Overall Status
Completed
CT.gov ID
NCT01253187
Collaborator
(none)
44
1
3
11
4
Study Details
Study Description
Brief 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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
44 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Open-label, Randomized, Three-fold Crossover Study to Investigate the Bioequivalence of Two Different Tablet Formulations Containing 0.02 mg Ethinylestradiol (EE) and 3 mg Drospirenone (DRSP) Without [SH T00186D] and With [SH T04532B] 0.451 mg L-mefolinate (Metafolin), and to Investigate the Bioequivalence of Two Different Tablet Formulations Containing 0.451 mg L-mefolinate (Metafolin) Without [SH T04532C] and With 0.02 mg EE/ 3 mg DRSP [SH T04532B] in 42 Healthy Young Women
Study Start Date
:
Oct 1, 2006
Actual Primary Completion Date
:
Sep 1, 2007
Actual Study Completion Date
:
Sep 1, 2007
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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)
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.
|
| 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)
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.
|
| 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)
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.
|
Outcome Measures
Primary Outcome Measures
- Mean Maximum Concentration (Cmax) of EE Incl. Bioequivalence (BE) Evaluation [up to 96 hours after administration]
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
- Mean Area Under the Concentration-time Curve From Administration to the Last Measurement [AUC(0-tlast)] of EE Incl. Bioequivalence (BE) Evaluation [up to 96 hours after administration]
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
- Mean Maximum Concentration (Cmax) of DRSP Incl. Bioequivalence (BE) Evaluation [up to 168 hours after administration]
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
- Mean Area Under the Concentration-time Curve From Administration to the Last Measurement [AUC(0-tlast)] of DRSP Incl. Bioequivalence (BE) Evaluation [up to 168 hours after administration]
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
- Mean Maximum Concentration (Cmax) of L-5-methyl-THF (Baseline Corrected) Incl. Bioequivalence (BE) Evaluation [up to 12 hours after administration]
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.
- 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 [up to 12 hours after administration]
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.
- Mean Maximum Concentration (Cmax) of L-5-methyl-THF (Baseline Uncorrected) Incl. Bioequivalence (BE) Evaluation [up to 12 hours after administration]
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.
- 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 [up to 12 hours after administration]
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.
Secondary Outcome Measures
- Time to Reach Maximum Concentration (Tmax) of EE [up to 96 hours after administration]
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
- Mean Area Under the Concentration-time Curve From Administration up to 72h AUC(0-72h) of DRSP [up to 72 hours after administration]
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 to Reach Maximum Concentration (Tmax) of DRSP [up to 168 hours after administration]
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 to Reach Maximum Concentration (Tmax) of L-5-methyl-THF [up to 12 hours after administration]
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
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 38 Years
Sexes Eligible for Study:
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:
-
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Dinox B.V. | Groningen | Netherlands | 9713GZ |
Sponsors and Collaborators
- Bayer
Investigators
- Study Director: Bayer Study Director, Bayer
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
,
,
ClinicalTrials.gov Identifier:
NCT01253187
Other Study ID Numbers:
- 91460
- 2005-003049-15
- 309664
First Posted:
Dec 3, 2010
Last Update Posted:
Aug 7, 2013
Last Verified:
Aug 1, 2013
Study Results
Participant Flow
| Recruitment Details | 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. |
|---|---|
| Pre-assignment Detail | 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. |
| Arm/Group Title | Treatment Sequence A: YAZ, EE20/DRSP/L-5-MTHF Ca, Metafolin | Treatment Sequence B: YAZ, Metafolin, EE20/DRSP/L-5-MTHF Ca | Treatment Sequence C: EE20/DRSP/L-5-MTHF Ca, YAZ, Metafolin | Treatment Sequence D: EE20/DRSP/L-5-MTHF Ca, Metafolin, YAZ | Treatment Sequence E: Metafolin, YAZ, EE20/DRSP/L-5-MTHF Ca | Treatment Sequence F: Metafolin, EE20/DRSP/L-5-MTHF Ca, YAZ |
|---|---|---|---|---|---|---|
| Arm/Group Description | 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]). | 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]). | 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]). | 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). | 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]). | 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 Title: Period 1 | ||||||
| STARTED | 7 | 8 | 7 | 7 | 9 | 6 |
| COMPLETED | 7 | 8 | 7 | 7 | 9 | 6 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
| Period Title: Period 1 | ||||||
| STARTED | 7 | 8 | 7 | 7 | 9 | 6 |
| COMPLETED | 7 | 8 | 7 | 7 | 8 | 6 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 1 | 0 |
| Period Title: Period 1 | ||||||
| STARTED | 7 | 8 | 7 | 7 | 8 | 6 |
| COMPLETED | 6 | 7 | 7 | 7 | 7 | 6 |
| NOT COMPLETED | 1 | 1 | 0 | 0 | 1 | 0 |
Baseline Characteristics
| Arm/Group Title | Entire Study Population |
|---|---|
| Arm/Group Description | Includes all participants treated |
| Overall Participants | 44 |
| Age (Years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [Years] |
26.3
(6.33)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
44
100%
|
| Male |
0
0%
|
Outcome Measures
| Title | Mean Maximum Concentration (Cmax) of EE Incl. Bioequivalence (BE) Evaluation |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Note that not all samples were evaluable for each outcome measure. Therefore the number of participants analyzed not necessarily matches the number of completers. |
| Arm/Group Title | EE 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) |
|---|---|---|
| Arm/Group Description | single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP) | 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]) |
| Measure Participants | 39 | 39 |
| Geometric Mean (95% Confidence Interval) [pg/mL] |
39.6
|
41.9
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | EE 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) |
|---|---|---|
| Comments | 38 volunteers qualified for statistical analysis of BE whereas all 39 volunteers with valid concentration time profiles were included in the pharmacokinetic (PK) analysis | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | A sample size of 6 volunteers per sequence was considered sufficient to establish bioequivalence, id est the 90%-confidence interval for the mean ratio is located completely within the equivalence interval limits of 80% and 125%. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | mean ratio |
| Estimated Value | 106.03 | |
| Confidence Interval |
() 90% 98.86 to 113.72 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Point 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% | |
| Title | Mean Area Under the Concentration-time Curve From Administration to the Last Measurement [AUC(0-tlast)] of EE Incl. Bioequivalence (BE) Evaluation |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Note that not all samples were evaluable for each outcome measure. Therefore the number of participants analyzed not necessarily matches the number of completers. |
| Arm/Group Title | EE 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) |
|---|---|---|
| Arm/Group Description | single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP) | 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]) |
| Measure Participants | 39 | 39 |
| Geometric Mean (95% Confidence Interval) [pg·h/mL] |
358
|
370
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | EE 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) |
|---|---|---|
| Comments | 38 volunteers qualified for statistical analysis of BE whereas all 39 volunteers with valid concentration time profiles were included in the pharmacokinetic (PK) analysis | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | A sample size of 6 volunteers per sequence was considered sufficient to establish bioequivalence, id est the 90%-confidence interval for the mean ratio is located completely within the equivalence interval limits of 80% and 125%. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | mean ratio |
| Estimated Value | 103.47 | |
| Confidence Interval |
() 90% 99.16 to 107.98 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Point 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% | |
| Title | Mean Maximum Concentration (Cmax) of DRSP Incl. Bioequivalence (BE) Evaluation |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Note that not all samples were evaluable for each outcome measure. Therefore the number of participants analyzed not necessarily matches the number of completers. |
| Arm/Group Title | EE 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) |
|---|---|---|
| Arm/Group Description | single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP) | 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]) |
| Measure Participants | 35 | 36 |
| Geometric Mean (95% Confidence Interval) [ng/mL] |
25.4
|
26.7
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | EE 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) |
|---|---|---|
| Comments | 33 volunteers qualified for statistical analysis of BE whereas all 35 (YAZ) and 36 (EE20/DRSP/L-5-MTHF Ca) volunteers with valid concentration time profiles were included in the pharmacokinetic (PK) analysis | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | A sample size of 6 volunteers per sequence was considered sufficient to establish bioequivalence, id est the 90%-confidence interval for the mean ratio is located completely within the equivalence interval limits of 80% and 125%. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | mean ratio |
| Estimated Value | 105.24 | |
| Confidence Interval |
() 90% 97.30 to 113.83 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Point 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% | |
| Title | Mean Area Under the Concentration-time Curve From Administration to the Last Measurement [AUC(0-tlast)] of DRSP Incl. Bioequivalence (BE) Evaluation |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Note that not all samples were evaluable for each outcome measure. Therefore the number of participants analyzed not necessarily matches the number of completers. |
| Arm/Group Title | EE 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) |
|---|---|---|
| Arm/Group Description | single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP) | 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]) |
| Measure Participants | 35 | 36 |
| Geometric Mean (95% Confidence Interval) [ng·h/mL] |
386
|
383
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | EE 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) |
|---|---|---|
| Comments | 33 volunteers qualified for statistical analysis of BE whereas all 35 (YAZ) and 36 (EE20/DRSP/L-5-MTHF Ca) volunteers with valid concentration time profiles were included in the pharmacokinetic (PK) analysis | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | A sample size of 6 volunteers per sequence was considered sufficient to establish bioequivalence, id est the 90%-confidence interval for the mean ratio is located completely within the equivalence interval limits of 80% and 125%. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | mean ratio |
| Estimated Value | 100.48 | |
| Confidence Interval |
() 90% 97.28 to 103.79 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Point 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% | |
| Title | Mean Maximum Concentration (Cmax) of L-5-methyl-THF (Baseline Corrected) Incl. Bioequivalence (BE) Evaluation |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Note that not all samples were evaluable for each outcome measure. Therefore the number of participants analyzed not necessarily matches the number of completers. |
| Arm/Group Title | 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) |
|---|---|---|
| Arm/Group Description | 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]) | single oral administration of 1 coated SHT04532C tablet, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium) [L-5-MTHF Ca] |
| Measure Participants | 39 | 40 |
| Geometric Mean (95% Confidence Interval) [nmol/L] |
44.3
|
44.2
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | EE 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) |
|---|---|---|
| Comments | 39 volunteers qualified for statistical analysis of BE whereas all 39 (EE20/DRSP/L-5-MTHF Ca) and 40 (Metafolin) volunteers with valid concentration time profiles were included in the pharmacokinetic (PK) analysis | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | A sample size of 6 volunteers per sequence was considered sufficient to establish bioequivalence, id est the 90%-confidence interval for the mean ratio is located completely within the equivalence interval limits of 80% and 125%. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | mean ratio |
| Estimated Value | 99.88 | |
| Confidence Interval |
() 90% 91.24 to 109.34 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Point 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% | |
| Title | 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 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Note that not all samples were evaluable for each outcome measure. Therefore the number of participants analyzed not necessarily matches the number of completers. |
| Arm/Group Title | 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) |
|---|---|---|
| Arm/Group Description | 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]) | single oral administration of 1 coated SHT04532C tablet, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium [L-5-MTHF Ca]) |
| Measure Participants | 39 | 40 |
| Geometric Mean (95% Confidence Interval) [nmol·h/L] |
214
|
217
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | EE 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) |
|---|---|---|
| Comments | 39 volunteers qualified for statistical analysis of BE whereas all 39 (EE20/DRSP/L-5-MTHF Ca) and 40 (Metafolin) volunteers with valid concentration time profiles were included in the pharmacokinetic (PK) analysis | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | A sample size of 6 volunteers per sequence was considered sufficient to establish bioequivalence, id est the 90%-confidence interval for the mean ratio is located completely within the equivalence interval limits of 80% and 125%. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | mean ratio |
| Estimated Value | 98.16 | |
| Confidence Interval |
() 90% 93.95 to 102.57 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Point 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% | |
| Title | Mean Maximum Concentration (Cmax) of L-5-methyl-THF (Baseline Uncorrected) Incl. Bioequivalence (BE) Evaluation |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Note that not all samples were evaluable for each outcome measure. Therefore the number of participants analyzed not necessarily matches the number of completers. |
| Arm/Group Title | 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) |
|---|---|---|
| Arm/Group Description | 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]) | single oral administration of 1 coated SHT04532C tablet, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium [L-5-MTHF Ca]) |
| Measure Participants | 40 | 40 |
| Geometric Mean (95% Confidence Interval) [nmol/L] |
57.9
|
57.7
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | EE 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) |
|---|---|---|
| Comments | 40 volunteers qualified for statistical analysis of BE and all 40 volunteers with valid concentration time profiles were included in the pharmacokinetic (PK) analysis | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | A sample size of 6 volunteers per sequence was considered sufficient to establish bioequivalence, id est the 90%-confidence interval for the mean ratio is located completely within the equivalence interval limits of 80% and 125%. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | mean ratio |
| Estimated Value | 100.28 | |
| Confidence Interval |
() 90% 93.15 to 107.95 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Point 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% | |
| Title | 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 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Note that not all samples were evaluable for each outcome measure. Therefore the number of participants analyzed not necessarily matches the number of completers. |
| Arm/Group Title | 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) |
|---|---|---|
| Arm/Group Description | 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]) | single oral administration of 1 coated SHT04532C tablet, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium [L-5-MTHF Ca]) |
| Measure Participants | 40 | 40 |
| Geometric Mean (95% Confidence Interval) [nmol·h/L] |
370
|
370
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | EE 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) |
|---|---|---|
| Comments | 40 volunteers qualified for statistical analysis of BE and all 40 volunteers with valid concentration time profiles were included in the pharmacokinetic (PK) analysis | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | A sample size of 6 volunteers per sequence was considered sufficient to establish bioequivalence, id est the 90%-confidence interval for the mean ratio is located completely within the equivalence interval limits of 80% and 125%. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | mean ratio |
| Estimated Value | 99.88 | |
| Confidence Interval |
() 90% 95.38 to 104.58 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Point 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% | |
| Title | Time to Reach Maximum Concentration (Tmax) of EE |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Note that not all samples were evaluable for each outcome measure. Therefore the number of participants analyzed not necessarily matches the number of completers. |
| Arm/Group Title | EE 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) |
|---|---|---|
| Arm/Group Description | single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP) | 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]) |
| Measure Participants | 39 | 39 |
| Median (Full Range) [hours] |
1.50
|
1.52
|
| Title | Mean Area Under the Concentration-time Curve From Administration up to 72h AUC(0-72h) of DRSP |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Note that not all samples were evaluable for each outcome measure. Therefore the number of participants analyzed not necessarily matches the number of completers. |
| Arm/Group Title | EE 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) |
|---|---|---|
| Arm/Group Description | single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP) | 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]) |
| Measure Participants | 34 | 36 |
| Geometric Mean (95% Confidence Interval) [ng·h/mL] |
350
|
344
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | EE 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) |
|---|---|---|
| Comments | 32 volunteers qualified for statistical analysis of BE whereas all 34 (YAZ) and 36 (EE20/DRSP/L-5-MTHF Ca) volunteers with valid concentration time profiles were included in the pharmacokinetic (PK) analysis | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | A sample size of 6 volunteers per sequence was considered sufficient to establish bioequivalence, id est the 90%-confidence interval for the mean ratio is located completely within the equivalence interval limits of 80% and 125%. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | mean ratio |
| Estimated Value | 100.30 | |
| Confidence Interval |
() 90% 97.65 to 103.02 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Point 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% | |
| Title | Time to Reach Maximum Concentration (Tmax) of DRSP |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Note that not all samples were evaluable for each outcome measure. Therefore the number of participants analyzed not necessarily matches the number of completers. |
| Arm/Group Title | EE 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) |
|---|---|---|
| Arm/Group Description | single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP) | 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]) |
| Measure Participants | 35 | 36 |
| Median (Full Range) [hours] |
2.00
|
2.00
|
| Title | Time to Reach Maximum Concentration (Tmax) of L-5-methyl-THF |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Note that not all samples were evaluable for each outcome measure. Therefore the number of participants analyzed not necessarily matches the number of completers. |
| Arm/Group Title | 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) |
|---|---|---|
| Arm/Group Description | 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]) | single oral administration of 1 coated SHT04532C tablet, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium [L-5-MTHF Ca]) |
| Measure Participants | 40 | 40 |
| Median (Full Range) [hours] |
0.50
|
0.50
|
Adverse Events
| Time Frame | ||||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | EE 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) | |||
| Arm/Group Description | single oral administration of 1 film-coated SHT00186D tablet (YAZ), containing 0.020 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP) | 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]) | single oral administration of 1 coated SHT04532C tablet, containing 0.451 mg Metafolin (L-5-methyltetrahydrofolate calcium [MTHF-Ca]) | |||
All Cause Mortality |
||||||
| EE 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) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| EE 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) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/43 (0%) | 0/41 (0%) | 0/43 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| EE 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) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 37/43 (86%) | 30/41 (73.2%) | 34/43 (79.1%) | |||
| Blood and lymphatic system disorders | ||||||
| Lymphadenopathy | 0/43 (0%) | 0 | 0/41 (0%) | 0 | 1/43 (2.3%) | 1 |
| Cardiac disorders | ||||||
| Palpitations | 2/43 (4.7%) | 2 | 0/41 (0%) | 0 | 0/43 (0%) | 0 |
| Ear and labyrinth disorders | ||||||
| Ear pain | 0/43 (0%) | 0 | 1/41 (2.4%) | 1 | 0/43 (0%) | 0 |
| Eye disorders | ||||||
| Conjunctivitis | 0/43 (0%) | 0 | 1/41 (2.4%) | 1 | 0/43 (0%) | 0 |
| Dry eye | 0/43 (0%) | 0 | 1/41 (2.4%) | 1 | 0/43 (0%) | 0 |
| Eyelid irritation | 0/43 (0%) | 0 | 0/41 (0%) | 0 | 1/43 (2.3%) | 1 |
| Blepharospasm | 1/43 (2.3%) | 1 | 0/41 (0%) | 0 | 0/43 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Abdominal discomfort | 4/43 (9.3%) | 4 | 2/41 (4.9%) | 2 | 1/43 (2.3%) | 1 |
| Abdominal distension | 1/43 (2.3%) | 1 | 0/41 (0%) | 0 | 0/43 (0%) | 0 |
| Abdominal pain | 2/43 (4.7%) | 2 | 4/41 (9.8%) | 4 | 1/43 (2.3%) | 1 |
| Abdominal pain lower | 0/43 (0%) | 0 | 1/41 (2.4%) | 1 | 0/43 (0%) | 0 |
| Diarrhoea | 7/43 (16.3%) | 7 | 5/41 (12.2%) | 5 | 2/43 (4.7%) | 2 |
| Dry mouth | 0/43 (0%) | 0 | 1/41 (2.4%) | 1 | 0/43 (0%) | 0 |
| Eructation | 1/43 (2.3%) | 1 | 0/41 (0%) | 0 | 0/43 (0%) | 0 |
| Nausea | 6/43 (14%) | 6 | 11/41 (26.8%) | 11 | 5/43 (11.6%) | 5 |
| Vomiting | 1/43 (2.3%) | 1 | 4/41 (9.8%) | 4 | 2/43 (4.7%) | 2 |
| General disorders | ||||||
| Asthenia | 4/43 (9.3%) | 4 | 0/41 (0%) | 0 | 0/43 (0%) | 0 |
| Catheter site haematoma | 0/43 (0%) | 0 | 1/41 (2.4%) | 1 | 0/43 (0%) | 0 |
| Catheter site pain | 1/43 (2.3%) | 1 | 3/41 (7.3%) | 3 | 0/43 (0%) | 0 |
| Catheter site related reaction | 2/43 (4.7%) | 3 | 1/41 (2.4%) | 1 | 0/43 (0%) | 0 |
| Chest discomfort | 0/43 (0%) | 0 | 1/41 (2.4%) | 3 | 0/43 (0%) | 0 |
| Discomfort | 1/43 (2.3%) | 1 | 0/41 (0%) | 0 | 1/43 (2.3%) | 1 |
| Fatigue | 5/43 (11.6%) | 6 | 5/41 (12.2%) | 6 | 2/43 (4.7%) | 2 |
| Feeling cold | 1/43 (2.3%) | 1 | 0/41 (0%) | 0 | 0/43 (0%) | 0 |
| Influenza like illness | 1/43 (2.3%) | 1 | 0/41 (0%) | 0 | 0/43 (0%) | 0 |
| Orthostatic intolerance | 1/43 (2.3%) | 1 | 0/41 (0%) | 0 | 0/43 (0%) | 0 |
| Peripheral coldness | 2/43 (4.7%) | 2 | 0/41 (0%) | 0 | 0/43 (0%) | 0 |
| Puncture site pain | 1/43 (2.3%) | 1 | 0/41 (0%) | 0 | 0/43 (0%) | 0 |
| Thirst | 1/43 (2.3%) | 1 | 0/41 (0%) | 0 | 0/43 (0%) | 0 |
| Vessel puncture site pain | 1/43 (2.3%) | 1 | 0/41 (0%) | 0 | 0/43 (0%) | 0 |
| Immune system disorders | ||||||
| Seasonal allergy | 1/43 (2.3%) | 1 | 0/41 (0%) | 0 | 1/43 (2.3%) | 1 |
| Infections and infestations | ||||||
| Acarodermatitis | 0/43 (0%) | 0 | 0/41 (0%) | 0 | 1/43 (2.3%) | 1 |
| Influenza | 1/43 (2.3%) | 1 | 2/41 (4.9%) | 2 | 1/43 (2.3%) | 1 |
| Nasopharyngitis | 2/43 (4.7%) | 2 | 1/41 (2.4%) | 1 | 3/43 (7%) | 3 |
| Rhinitis | 0/43 (0%) | 0 | 1/41 (2.4%) | 1 | 0/43 (0%) | 0 |
| Upper respiratory tract infection | 0/43 (0%) | 0 | 0/41 (0%) | 0 | 1/43 (2.3%) | 1 |
| Urinary tract infection | 0/43 (0%) | 0 | 1/41 (2.4%) | 1 | 0/43 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Periorbital haematoma | 0/43 (0%) | 0 | 1/41 (2.4%) | 1 | 0/43 (0%) | 0 |
| Scratch | 1/43 (2.3%) | 1 | 0/41 (0%) | 0 | 0/43 (0%) | 0 |
| Investigations | ||||||
| Serum ferritin decreased | 7/43 (16.3%) | 7 | 6/41 (14.6%) | 6 | 8/43 (18.6%) | 8 |
| Weight increased | 1/43 (2.3%) | 1 | 0/41 (0%) | 0 | 0/43 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 2/43 (4.7%) | 2 | 0/41 (0%) | 0 | 0/43 (0%) | 0 |
| Back pain | 1/43 (2.3%) | 1 | 0/41 (0%) | 0 | 0/43 (0%) | 0 |
| Musculoskeletal discomfort | 1/43 (2.3%) | 1 | 0/41 (0%) | 0 | 0/43 (0%) | 0 |
| Neck pain | 0/43 (0%) | 0 | 1/41 (2.4%) | 1 | 1/43 (2.3%) | 1 |
| Pain in extremity | 1/43 (2.3%) | 1 | 0/41 (0%) | 0 | 0/43 (0%) | 0 |
| Nervous system disorders | ||||||
| Dizziness | 2/43 (4.7%) | 4 | 3/41 (7.3%) | 3 | 1/43 (2.3%) | 1 |
| Headache | 15/43 (34.9%) | 17 | 9/41 (22%) | 11 | 11/43 (25.6%) | 13 |
| Hypoaesthesia | 1/43 (2.3%) | 2 | 1/41 (2.4%) | 1 | 0/43 (0%) | 0 |
| Syncope vasovagal | 7/43 (16.3%) | 8 | 3/41 (7.3%) | 4 | 2/43 (4.7%) | 2 |
| Tremor | 2/43 (4.7%) | 2 | 0/41 (0%) | 0 | 0/43 (0%) | 0 |
| Psychiatric disorders | ||||||
| Anxiety | 1/43 (2.3%) | 1 | 0/41 (0%) | 0 | 0/43 (0%) | 0 |
| Emotional disorder | 1/43 (2.3%) | 1 | 0/41 (0%) | 0 | 0/43 (0%) | 0 |
| Restlessness | 0/43 (0%) | 0 | 1/41 (2.4%) | 1 | 0/43 (0%) | 0 |
| Sleep disorder | 0/43 (0%) | 0 | 1/41 (2.4%) | 1 | 0/43 (0%) | 0 |
| Reproductive system and breast disorders | ||||||
| Dysmenorrhoea | 0/43 (0%) | 0 | 2/41 (4.9%) | 2 | 1/43 (2.3%) | 1 |
| Metrorrhagia | 10/43 (23.3%) | 10 | 9/41 (22%) | 9 | 0/43 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Apnoea | 1/43 (2.3%) | 1 | 0/41 (0%) | 0 | 0/43 (0%) | 0 |
| Dyspnoea | 1/43 (2.3%) | 1 | 0/41 (0%) | 0 | 0/43 (0%) | 0 |
| Pharyngolaryngeal pain | 0/43 (0%) | 0 | 1/41 (2.4%) | 1 | 0/43 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||
| Acne | 0/43 (0%) | 0 | 1/41 (2.4%) | 1 | 1/43 (2.3%) | 1 |
| Blister | 0/43 (0%) | 0 | 0/41 (0%) | 0 | 1/43 (2.3%) | 1 |
| Dermal cyst | 1/43 (2.3%) | 1 | 0/41 (0%) | 0 | 0/43 (0%) | 0 |
| Dermatitis | 0/43 (0%) | 0 | 0/41 (0%) | 0 | 1/43 (2.3%) | 1 |
| Dry skin | 0/43 (0%) | 0 | 1/41 (2.4%) | 1 | 0/43 (0%) | 0 |
| Surgical and medical procedures | ||||||
| Dental treatment | 1/43 (2.3%) | 1 | 0/41 (0%) | 0 | 0/43 (0%) | 0 |
| Vascular disorders | ||||||
| Flushing | 1/43 (2.3%) | 1 | 0/41 (0%) | 0 | 0/43 (0%) | 0 |
| Haematoma | 1/43 (2.3%) | 1 | 0/41 (0%) | 0 | 0/43 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | Therapeutic Area Head |
|---|---|
| Organization | Bayer HealthCare AG |
| Phone | |
| clinical-trials-contact@bayerhealthcare.com |
Responsible Party:
,
,
ClinicalTrials.gov Identifier:
NCT01253187
Other Study ID Numbers:
- 91460
- 2005-003049-15
- 309664
First Posted:
Dec 3, 2010
Last Update Posted:
Aug 7, 2013
Last Verified:
Aug 1, 2013