Healthy
Conditions
Brief summary
Investigate the effect of multiple oral doses of BI 207127 + faldaprevir (FDV) on the multiple dose pharmacokinetics of ethinylestradiol and levonorgestrel (Microgynon®) in healthy premenopausal female volunteers.
Interventions
DRUGfaldaprevir
oral doses for 10 days (period B)
DRUGMicrogynon®
oral doses for 23 days (period A+B)
DRUGBI 207127
oral doses for 10 days (period B)
Sponsors
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy female subjects * Age 18 to 35 years (inclusive) * Body Mass Index 20-29.9 kg/m2 * Use of hormonal contraception (i.e. oral contraceptives, hormonal contraceptive vaginal ring, but not hormone-containing intrauterine devices, depot injections or contraceptive implants)
Exclusion criteria
* Any relevant deviation from healthy conditions * Subject is assessed by the investigator as unsuitable for inclusion, for instance, because considered not able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study * Positive pregnancy test, pregnancy or planning to become pregnant within 1 month of study completion, or lactation * Any relevant finding of the gynaecological examination * Thrombotic predisposition according to thrombophilic testing * Existing or history of arterial thrombotic or embolic processes, conditions which predispose to them e.g. disorders of the clotting processes, valvular heart disease and atrial fibrillation * Existing or history of confirmed venous thromboembolism, family history of venous thromboembolism, and other known risk factors for venous thromboembolism. * Relevant varicosis * No use of an additional contraceptive method from screening examination until 1 month after last study drug administration (acceptable methods are considered to be barrier methods, sexual abstinence, non-hormone-containing intrauterine device, or vasectomisation for the male partner). Use of hormone-containing intrauterine device, depot injection or contraceptive implants * Any history of relevant liver diseases (e.g. disturbances of liver function, jaundice or persistent itching during a previous pregnancy, Dubin-Johnson syndrome, Rotor syndrome, or previous or existing liver tumours) * AST (aspartate transaminase) and/or ALT (alanine transaminase) \> 1.5 ULN (upper limit of normal)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUCtau,ss of Ethinylestradiol | Visit (V)3: 2 hours(h) pre dose, 240, 264, 288, 288.5, 289, 289.5, 290, 291, 292, 294, 296, 298, 300 h post dose; V4: 0, 24, 48, 72, 96, 120, 144, 168, 192, 216, 216.5, 217, 217.5, 218, 219, 220, 222, 224, 226, 228, 240 h post dose for oral contraceptives | Area under the concentration-time curve of ethinylestradiol in plasma at steady state over a uniform dosing interval t (AUCtau,ss). |
| Cmax,ss of Ethinylestradiol | Visit (V)3: 2 hours(h) pre dose, 240, 264, 288, 288.5, 289, 289.5, 290, 291, 292, 294, 296, 298, 300 h post dose; V4: 0, 24, 48, 72, 96, 120, 144, 168, 192, 216, 216.5, 217, 217.5, 218, 219, 220, 222, 224, 226, 228, 240 h post dose for oral contraceptives | Maximum measured concentration of ethinylestradiol in plasma at steady state over a uniform dosing interval t |
| C24,ss of Ethinylestradiol | Visit (V)3: 2 hours(h) pre dose, 240, 264, 288, 288.5, 289, 289.5, 290, 291, 292, 294, 296, 298, 300 h post dose; V4: 0, 24, 48, 72, 96, 120, 144, 168, 192, 216, 216.5, 217, 217.5, 218, 219, 220, 222, 224, 226, 228, 240 h post dose for oral contraceptives | Measured concentration of ethinylestradiol in plasma at steady state 24 hours after drug administration. |
| AUCtau,ss of Levonogestrel | Visit (V)3: 2 hours(h) pre dose, 240, 264, 288, 288.5, 289, 289.5, 290, 291, 292, 294, 296, 298, 300 h post dose; V4: 0, 24, 48, 72, 96, 120, 144, 168, 192, 216, 216.5, 217, 217.5, 218, 219, 220, 222, 224, 226, 228, 240 h post dose for oral contraceptives | Area under the concentration-time curve of levonogestrel in plasma at steady state over a uniform dosing interval t. |
| Cmax,ss of Levonogestrel | Visit (V)3: 2 hours(h) pre dose, 240, 264, 288, 288.5, 289, 289.5, 290, 291, 292, 294, 296, 298, 300 h post dose; V4: 0, 24, 48, 72, 96, 120, 144, 168, 192, 216, 216.5, 217, 217.5, 218, 219, 220, 222, 224, 226, 228, 240 h post dose for oral contraceptives | Maximum measured concentration of levonogestrel in plasma at steady state over a uniform dosing interval t. |
| C24,ss of Levonogestrel | Visit (V)3: 2 hours(h) pre dose, 240, 264, 288, 288.5, 289, 289.5, 290, 291, 292, 294, 296, 298, 300 h post dose; V4: 0, 24, 48, 72, 96, 120, 144, 168, 192, 216, 216.5, 217, 217.5, 218, 219, 220, 222, 224, 226, 228, 240 h post dose for oral contraceptives | Measured concentration of levonogestrel in plasma at steady state 24 hours after drug administration. |
Countries
Germany
Participant flow
Recruitment details
This trial was planned to include 18 healthy premenopausal female subjects. Because this trial was prematurely discontinued during the run-in period, only 16 subjects were entered.
Participants by arm
| Arm | Count |
|---|---|
| Deleobuvir + Faldaprevir + Microgynon This was an open-label, 2-period, fixed-sequence study. After a run-in period of 28 to 56 days (treatment with Microgynon® once daily for 21 to 49 days, depending on the menstrual cycle, followed by a tablet-free interval of 7 days), subjects were to begin the first (reference) treatment period of Microgynon® alone for 13 days, immediately (without washout) followed by the second (test) treatment period of Microgynon® plus deleobuvir+faldaprevir for 10 days. | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | Deleobuvir + Faldaprevir + Microgynon |
|---|---|
| Age, Continuous | 26.5 years STANDARD_DEVIATION 3.7 |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 4 / 16 |
| serious Total, serious adverse events | 0 / 16 |
Outcome results
Primary
AUCtau,ss of Ethinylestradiol
Area under the concentration-time curve of ethinylestradiol in plasma at steady state over a uniform dosing interval t (AUCtau,ss).
Time frame: Visit (V)3: 2 hours(h) pre dose, 240, 264, 288, 288.5, 289, 289.5, 290, 291, 292, 294, 296, 298, 300 h post dose; V4: 0, 24, 48, 72, 96, 120, 144, 168, 192, 216, 216.5, 217, 217.5, 218, 219, 220, 222, 224, 226, 228, 240 h post dose for oral contraceptives
Population: Since this trial was prematurely discontinued during the run-in period, no blood samples for pharmacokinetics were collected and therefore no pharmacokinetic endpoints could be determined.
Primary
AUCtau,ss of Levonogestrel
Area under the concentration-time curve of levonogestrel in plasma at steady state over a uniform dosing interval t.
Time frame: Visit (V)3: 2 hours(h) pre dose, 240, 264, 288, 288.5, 289, 289.5, 290, 291, 292, 294, 296, 298, 300 h post dose; V4: 0, 24, 48, 72, 96, 120, 144, 168, 192, 216, 216.5, 217, 217.5, 218, 219, 220, 222, 224, 226, 228, 240 h post dose for oral contraceptives
Population: Since this trial was prematurely discontinued during the run-in period, no blood samples for pharmacokinetics were collected and therefore no pharmacokinetic endpoints could be determined.
Primary
C24,ss of Ethinylestradiol
Measured concentration of ethinylestradiol in plasma at steady state 24 hours after drug administration.
Time frame: Visit (V)3: 2 hours(h) pre dose, 240, 264, 288, 288.5, 289, 289.5, 290, 291, 292, 294, 296, 298, 300 h post dose; V4: 0, 24, 48, 72, 96, 120, 144, 168, 192, 216, 216.5, 217, 217.5, 218, 219, 220, 222, 224, 226, 228, 240 h post dose for oral contraceptives
Population: Since this trial was prematurely discontinued during the run-in period, no blood samples for pharmacokinetics were collected and therefore no pharmacokinetic endpoints could be determined.
Primary
C24,ss of Levonogestrel
Measured concentration of levonogestrel in plasma at steady state 24 hours after drug administration.
Time frame: Visit (V)3: 2 hours(h) pre dose, 240, 264, 288, 288.5, 289, 289.5, 290, 291, 292, 294, 296, 298, 300 h post dose; V4: 0, 24, 48, 72, 96, 120, 144, 168, 192, 216, 216.5, 217, 217.5, 218, 219, 220, 222, 224, 226, 228, 240 h post dose for oral contraceptives
Population: Since this trial was prematurely discontinued during the run-in period, no blood samples for pharmacokinetics were collected and therefore no pharmacokinetic endpoints could be determined.
Primary
Cmax,ss of Ethinylestradiol
Maximum measured concentration of ethinylestradiol in plasma at steady state over a uniform dosing interval t
Time frame: Visit (V)3: 2 hours(h) pre dose, 240, 264, 288, 288.5, 289, 289.5, 290, 291, 292, 294, 296, 298, 300 h post dose; V4: 0, 24, 48, 72, 96, 120, 144, 168, 192, 216, 216.5, 217, 217.5, 218, 219, 220, 222, 224, 226, 228, 240 h post dose for oral contraceptives
Population: Since this trial was prematurely discontinued during the run-in period, no blood samples for pharmacokinetics were collected and therefore no pharmacokinetic endpoints could be determined.
Primary
Cmax,ss of Levonogestrel
Maximum measured concentration of levonogestrel in plasma at steady state over a uniform dosing interval t.
Time frame: Visit (V)3: 2 hours(h) pre dose, 240, 264, 288, 288.5, 289, 289.5, 290, 291, 292, 294, 296, 298, 300 h post dose; V4: 0, 24, 48, 72, 96, 120, 144, 168, 192, 216, 216.5, 217, 217.5, 218, 219, 220, 222, 224, 226, 228, 240 h post dose for oral contraceptives
Population: Since this trial was prematurely discontinued during the run-in period, no blood samples for pharmacokinetics were collected and therefore no pharmacokinetic endpoints could be determined.