Effect of Concomitant Use of an Antimycotic, an Antibiotic, a Spermicide or Tampons on Pharmacokinetics of Anastrozole and Levonorgestrel Released From Intra-vaginal Ring

Study Overview
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Brief Summary
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To investigate the pharmacokinetic effect of a vaginally administered antimycotic (miconazole), antibiotic (clindamycin), spermicide (nonoxynol-9) or the concomitant use of tampons during the use of an intravaginal ring releasing anastrozole and levonorgestrel

Official Title
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A Parallel Group, Randomized, Open-label Study to Investigate the Effect of the Intravaginally Administered Antimycotic Miconazole, Antibiotic Clindamycin, Spermicide Nonoxynol-9, or Co-usage of Tampons on 3 Consecutive Days on the Pharmacokinetics of Anastrozole and Levonorgestrel Released From an Intra-vaginal Ring in Healthy Young Women

Conditions
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Endometriosis

Intervention / Treatment
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* Drug: Anastrozole / Levonorgestrel (BAY98-7196)
* Drug: Gyno-Daktarin
* Drug: Sobelin vaginal creme
* Drug: Patentex oval
* Other: Tampon


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy pre-menopausal female subject. Age: 18 - 50 years (inclusive) at the first screening visit. For the subject > 45 years follicle stimulating hormone (FSH) will be investigated at the second screening visit to confirm the pre-menopausal status (FSH < 40 IU/L in serum). Body mass index (BMI ) above or equal 18, and below or equal 30 kg / m² at the first screening visit. Adequate venous access. Ability to understand and follow study-related instructions Agreement to use adequate non-hormonal contraception. Confirmation of the subject's health insurance coverage prior to the first screening examination/visit. Exclusion Criteria: Incompletely cured pre-existing diseases for which it can be assumed that the absorption, distribution, metabolism, elimination and effects of the study drugs will not be normal. Thrombophlebitis, venous / arterial thromboembolic diseases (particularly deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction). Presence or history of prodromata of thrombosis (e.g. transient ischemic attack, angina pectoris). Known hypersensitivity to the study medications (active substances or excipients of the preparations). Regular intake of medication other than hormonal contraceptives. Use of systemic or topical medication or substances which oppose the study objectives or which might influence them within 4 weeks before first administration of the study medication, Smoking of more than 10 cigarettes daily; if the subject is a smoker: subject is older than 35 years Suspicion of or known current drug, medicine or alcohol abuse (including anabolics, high-dose vitamins). Abnormal cervical smear Previous ectopic pregnancy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BAY98-7196<br>Investigate the pharmacokinetics effect of a vaginally administered antimycotic (miconazole) during the use of an intra-vaginal ring (IVR) releasing anastrozole (ATZ) and levonorgestrel (LNG) | Drug: Anastrozole / Levonorgestrel (BAY98-7196)<br>* Release rate of the IVR: 1050 μg/d ATZ + 40 μg/d LNG<br>Drug: Gyno-Daktarin<br>* 400 mg miconazole nitrate per day for 3 consecutive days<br>|
| Experimental: Administered Antibiotic<br>Investigate the pharmacokinetics effect of a vaginally administered antibiotic (clindamycin) during the use of an IVR releasing ATZ and LNG | Drug: Anastrozole / Levonorgestrel (BAY98-7196)<br>* Release rate of the IVR: 1050 μg/d ATZ + 40 μg/d LNG<br>Drug: Sobelin vaginal creme<br>* 100 mg clindamycin 2-dihydrogen phosphat per day for 3 consecutive days<br>|
| Experimental: Administered Spermicide<br>Investigate the pharmacokinetics effect of a vaginally administered spermicide (nonoxynol-9) during the use of an IVR releasing ATZ and LNG | Drug: Anastrozole / Levonorgestrel (BAY98-7196)<br>* Release rate of the IVR: 1050 μg/d ATZ + 40 μg/d LNG<br>Drug: Patentex oval<br>* 75 mg Nonoxynol-9 per day for 3 consecutive days<br>|
| Experimental: Tampons<br>Investigate the pharmacokinetics effect of the concomitant use of tampons during the use of an IVR releasing ATZ and LNG; investigate the pharmacokinetics over an extended IVR wearing period of 35 days | Drug: Anastrozole / Levonorgestrel (BAY98-7196)<br>* Release rate of the IVR: 1050 μg/d ATZ + 40 μg/d LNG<br>Other: Tampon<br> <br> * Other names: Tampons (3 changes per day) for 3 consecutive days;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average concentration (Cav) anastrozole after insertion of the intra-vaginal ring for all groups |  | 202-226h | 
| Average concentration (Cav) anastrozole after insertion of the intra-vaginal ring for all groups |  | 226-298h | 
| Average concentration (Cav) anastrozole after insertion of the intra-vaginal ring for all groups |  | 226-384h | 
| Average concentration (Cav) anastrozole after insertion of the intra-vaginal ring for Tampon group |  | 466-490h | 
| Average concentration (Cav) anastrozole after insertion of the intra-vaginal ring for Tampon group |  | 490-562h | 
| Average concentration (Cav) anastrozole after insertion of the intra-vaginal ring for Tampon group |  | 490-648h | 
| Average concentration (Cav) levonorgestrel after insertion of the intra-vaginal ring for all groups |  | 202-226h | 
| Average concentration (Cav) levonorgestrel after insertion of the intra-vaginal ring for all groups |  | 226-298h | 
| Average concentration (Cav) levonorgestrel after insertion of the intra-vaginal ring for all groups |  | 226-384h | 
| Average concentration (Cav) levonorgestrel after insertion of the intra-vaginal ring for Tampon group |  | 466-490h | 
| Average concentration (Cav) levonorgestrel after insertion of the intra-vaginal ring for Tampon group |  | 490-562h | 
| Average concentration (Cav) levonorgestrel after insertion of the intra-vaginal ring for Tampon group |  | 490-648h | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed plasma concentration before co-medication or tampons (Cmax) |  | 490h | 
| Time to reach maximum observed concentration before co-medication or tampons (tmax) |  | 490h | 
| Plasma concentration 28 days after intra-vaginal ring (IVR) insertion (Treatment group D, Day 29) (C(28d)) |  | 672h | 
| Plasma concentration 35 days after IVR insertion (Treatment group D, Day 36)(C(35d)) |  | 840h | 
| Average concentration in the extended wearing period (Treatment D, Days 29-36 using the same IVR) |  | 672-840h | 
| Terminal half-life associated with the terminal slope after removal of IVR (t1/2) |  | Up to 6 days after IVR removal | 
| Number of participants with adverse events as a measure of safety and tolerability |  | Up to 14 days after IVR removal |