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

Phase 1

Completed

• Conditions: Endometriosis
• Interventions: Drug: Anastrozole / Levonorgestrel (BAY98-7196); Other: Tampon; Drug: Gyno-Daktarin; Drug: Sobelin vaginal creme; Drug: Patentex oval

• Registration Number: NCT02545452
• Lead Sponsor: Bayer

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-09-08
• Study First Submitted QC: 2015-09-09
• Study First Posted: 2015-09-10
• Study Start: 2015-09-15
• Primary Completion: 2016-03-14
• Study Completion: 2016-07-29
• Status Verified: 2017-07
• Last Update Submitted: 2017-07-21
• Last Update Posted: 2017-07-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 52

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tampons	Tampon	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
BAY98-7196	Anastrozole / Levonorgestrel (BAY98-7196)	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)
BAY98-7196	Gyno-Daktarin	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)
Administered Antibiotic	Anastrozole / Levonorgestrel (BAY98-7196)	Investigate the pharmacokinetics effect of a vaginally administered antibiotic (clindamycin) during the use of an IVR releasing ATZ and LNG
Administered Antibiotic	Sobelin vaginal creme	Investigate the pharmacokinetics effect of a vaginally administered antibiotic (clindamycin) during the use of an IVR releasing ATZ and LNG
Administered Spermicide	Anastrozole / Levonorgestrel (BAY98-7196)	Investigate the pharmacokinetics effect of a vaginally administered spermicide (nonoxynol-9) during the use of an IVR releasing ATZ and LNG
Administered Spermicide	Patentex oval	Investigate the pharmacokinetics effect of a vaginally administered spermicide (nonoxynol-9) during the use of an IVR releasing ATZ and LNG
Tampons	Anastrozole / Levonorgestrel (BAY98-7196)	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

Primary Outcome Measures

Name	Time	Method
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	490-648h
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	490-648h

Secondary Outcome Measures

Name	Time	Method
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