Hepatitis C, Chronic
Conditions
Brief summary
This study will investigate possible effect of multiple oral doses of BI 201335 on the steady state pharmacokinetics of ethinylestradiol and levonogestrel
Interventions
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
1\. Healthy female subjects
Exclusion criteria
1\. Any relevant deviation from healthy conditions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| C24,ss of Levonorgestrel | on day 13 of first period and on day 8 of second period 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00 h after drug administration | measured concentration of the analyte at the end of dosing interval under steady state conditions of levonorgestrel |
| AUCτ,ss of Levonorgestrel | on day 13 of first period and on day 8 of second period 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00 h after drug administration | Area under the curve over the dosing interval τ under steady state conditions of levonorgestrel |
| Cmax,ss of Levonorgestrel | on day 13 of first period and on day 8 of second period 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00 h after drug administration | maximum measured concentration over the uniform dosing interval under steady state conditions of levonorgestrel |
| AUCt,ss of Ethinylestradiol | on day 13 of first period and on day 8 of second period 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00 hours (h) after drug administration | Area under the curve over the dosing interval t under steady state conditions of ethinylestradiol |
| Cmax,ss of Ethinylestradiol | on day 13 of first period and on day 8 of second period 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00 h after drug administration | maximum measured concentration over the uniform dosing interval under steady state conditions of ethinylestradiol |
| C24,ss of Ethinylestradiol | on day 13 of first period and on day 8 of second period 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00 h after drug administration | measured concentration of the analyte at the end of dosing interval under steady state conditions of ethinylestradiol |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Drug Related Adverse Events | from drug administration up to 14 days | number of participants with investigator-defined drug related adverse events |
| Clinical Relevant Abnormalities for Vital Signs, Physical Examination, Blood Chemistry, Haematology, Urinanalysis and ECG. | from drug administration up to 14 days | Clinical relevant abnormalities for Vital Signs, Physical Examination, Blood Chemistry, Haematology, Urinanalysis and ECG. New abnormal findings or worsening of baseline conditions were reported as Adverse Events. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Subjects The trial was a nonrandomised, noncontrolled, open-label, 2-period fixed-sequence trial to evaluate the possible effect of multiple doses of faldaprevir on the multiple-dose pharmacokinetics of a combination of ethinylestradiol and levonorgestrel. The trial was to be performed in 16 healthy female volunteers. | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Microgynon+Faldaprevir | Adverse Event | 1 |
Baseline characteristics
| Characteristic | All Subjects |
|---|---|
| Age, Continuous | 28.4 years STANDARD_DEVIATION 5.1 |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 12 / 16 | 14 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 |
Outcome results
Primary
AUCt,ss of Ethinylestradiol
Area under the curve over the dosing interval t under steady state conditions of ethinylestradiol
Time frame: on day 13 of first period and on day 8 of second period 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00 hours (h) after drug administration
Population: Pharmacokinetic (PK) set: all subjects in the treated set who provided at least 1 observation for at least 1 primary pharmacokinetic endpoint, who did not have important protocol violations relevant to the evaluation of PK endpoints, and who did not have vomiting until 2·median tmax,ss of ethinylestradiol or levonorgestrel on Day 13 or on Day 8.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Microgynon | AUCt,ss of Ethinylestradiol | 1010 pg*h/mL | Geometric Coefficient of Variation 23.5 |
| Microgynon + Faldaprevir | AUCt,ss of Ethinylestradiol | 1450 pg*h/mL | Geometric Coefficient of Variation 27.8 |
Comparison: relative bioavailability comparison (Microgynon + Faldaprevir : Microgynon) of Ethinylestradiol90% CI: [133.84, 148.47]ANOVA
Primary
AUCτ,ss of Levonorgestrel
Area under the curve over the dosing interval τ under steady state conditions of levonorgestrel
Time frame: on day 13 of first period and on day 8 of second period 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00 h after drug administration
Population: PK set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Microgynon | AUCτ,ss of Levonorgestrel | 83.3 ng*h/mL | Geometric Coefficient of Variation 42 |
| Microgynon + Faldaprevir | AUCτ,ss of Levonorgestrel | 120 ng*h/mL | Geometric Coefficient of Variation 40.6 |
Comparison: relative bioavailability comparison (Microgynon + Faldaprevir : Microgynon) of Levonorgestrel90% CI: [136.4, 144.78]ANOVA
Primary
C24,ss of Ethinylestradiol
measured concentration of the analyte at the end of dosing interval under steady state conditions of ethinylestradiol
Time frame: on day 13 of first period and on day 8 of second period 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00 h after drug administration
Population: PK set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Microgynon | C24,ss of Ethinylestradiol | 19.1 pg/mL | Geometric Coefficient of Variation 32.9 |
| Microgynon + Faldaprevir | C24,ss of Ethinylestradiol | 33.2 pg/mL | Geometric Coefficient of Variation 42.9 |
Comparison: relative bioavailability comparison (Microgynon + Faldaprevir : Microgynon) of Ethinylestradiol90% CI: [160.2, 183.33]ANOVA
Primary
C24,ss of Levonorgestrel
measured concentration of the analyte at the end of dosing interval under steady state conditions of levonorgestrel
Time frame: on day 13 of first period and on day 8 of second period 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00 h after drug administration
Population: PK set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Microgynon | C24,ss of Levonorgestrel | 2.43 ng/mL | Geometric Coefficient of Variation 49.4 |
| Microgynon + Faldaprevir | C24,ss of Levonorgestrel | 3.85 ng/mL | Geometric Coefficient of Variation 47.9 |
Comparison: relative bioavailability comparison (Microgynon + Faldaprevir : Microgynon) of Levonorgestrel90% CI: [145.99, 162.14]ANOVA
Primary
Cmax,ss of Ethinylestradiol
maximum measured concentration over the uniform dosing interval under steady state conditions of ethinylestradiol
Time frame: on day 13 of first period and on day 8 of second period 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00 h after drug administration
Population: PK set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Microgynon | Cmax,ss of Ethinylestradiol | 108 pg/mL | Geometric Coefficient of Variation 23.6 |
| Microgynon + Faldaprevir | Cmax,ss of Ethinylestradiol | 127 pg/mL | Geometric Coefficient of Variation 25.1 |
Comparison: relative bioavailability comparison (Microgynon + Faldaprevir : Microgynon) of Ethinylestradiol90% CI: [105.49, 124.97]ANOVA
Primary
Cmax,ss of Levonorgestrel
maximum measured concentration over the uniform dosing interval under steady state conditions of levonorgestrel
Time frame: on day 13 of first period and on day 8 of second period 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00 h after drug administration
Population: PK set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Microgynon | Cmax,ss of Levonorgestrel | 7.57 ng/mL | Geometric Coefficient of Variation 34.9 |
| Microgynon + Faldaprevir | Cmax,ss of Levonorgestrel | 8.95 ng/mL | Geometric Coefficient of Variation 33.3 |
Comparison: relative bioavailability comparison (Microgynon + Faldaprevir : Microgynon) of Levonorgestrel90% CI: [110.81, 119.92]ANOVA
Secondary
Clinical Relevant Abnormalities for Vital Signs, Physical Examination, Blood Chemistry, Haematology, Urinanalysis and ECG.
Clinical relevant abnormalities for Vital Signs, Physical Examination, Blood Chemistry, Haematology, Urinanalysis and ECG. New abnormal findings or worsening of baseline conditions were reported as Adverse Events.
Time frame: from drug administration up to 14 days
Population: Treated set: This subject set included all 16 subjects who were administered trial medication and were documented to have taken at least 1 dose of investigational treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Microgynon | Clinical Relevant Abnormalities for Vital Signs, Physical Examination, Blood Chemistry, Haematology, Urinanalysis and ECG. | 0 participants |
| Microgynon + Faldaprevir | Clinical Relevant Abnormalities for Vital Signs, Physical Examination, Blood Chemistry, Haematology, Urinanalysis and ECG. | 0 participants |
Secondary
Number of Participants With Drug Related Adverse Events
number of participants with investigator-defined drug related adverse events
Time frame: from drug administration up to 14 days
Population: treated set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Microgynon | Number of Participants With Drug Related Adverse Events | 2 participants |
| Microgynon + Faldaprevir | Number of Participants With Drug Related Adverse Events | 15 participants |