Effect of BI 207127 + Faldaprevir on Blood Levels of Oral Contraceptives Containing Ethinylestradiol and Levonorgestrel

Study Overview
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Brief Summary
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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.

Official Title
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An Open-label, Two-period, Fixed-sequence, Phase I Trial to Evaluate the Effect of Multiple Doses of BI 207127 + Faldaprevir on the Multiple-dose Pharmacokinetics of a Combination of Ethinylestradiol and Levonorgestrel in Healthy Premenopausal Female Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: faldaprevir
* Drug: Microgynon®
* Drug: BI 207127


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 207127 + faldaprevir + Microgynon<br>Period A: Microgynon®; Period B: Microgynon® + FDV + BI 207127 | Drug: faldaprevir<br>* oral doses for 10 days (period B)<br>Drug: Microgynon®<br>* oral doses for 23 days (period A+B)<br>Drug: BI 207127<br>* oral doses for 10 days (period B)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 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 | 
| Cmax,ss of Ethinylestradiol | Maximum measured concentration of ethinylestradiol in plasma at steady state over a uniform dosing interval t | 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 | 
| C24,ss of Ethinylestradiol | Measured concentration of ethinylestradiol in plasma at steady state 24 hours after drug administration. | 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 | 
| AUCtau,ss of Levonogestrel | Area under the concentration-time curve of levonogestrel in plasma at steady state over a uniform dosing interval t. | 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 | 
| Cmax,ss of Levonogestrel | Maximum measured concentration of levonogestrel in plasma at steady state over a uniform dosing interval t. | 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 | 
| C24,ss of Levonogestrel | Measured concentration of levonogestrel in plasma at steady state 24 hours after drug administration. | 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 |