Clinical trial NCT02545452: Effect of Concomitant Use of an Antimycotic, an Antibiotic, a Spermicide or Tampons on Pharmacokinetics of Anastrozole and Levonorgestrel Released From Intra-vaginal Ring
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Endometriosis
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2015-09-10
Enrollment: 52
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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


Eligibility criteria: 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.

Primary outcomes:
measure: Average concentration (Cav) anastrozole after insertion of the intra-vaginal ring for all groups
timeFrame: 202-226h
measure: Average concentration (Cav) anastrozole after insertion of the intra-vaginal ring for all groups
timeFrame: 226-298h
measure: Average concentration (Cav) anastrozole after insertion of the intra-vaginal ring for all groups
timeFrame: 226-384h
measure: Average concentration (Cav) anastrozole after insertion of the intra-vaginal ring for Tampon group
timeFrame: 466-490h
measure: Average concentration (Cav) anastrozole after insertion of the intra-vaginal ring for Tampon group
timeFrame: 490-562h
measure: Average concentration (Cav) anastrozole after insertion of the intra-vaginal ring for Tampon group
timeFrame: 490-648h
measure: Average concentration (Cav) levonorgestrel after insertion of the intra-vaginal ring for all groups
timeFrame: 202-226h
measure: Average concentration (Cav) levonorgestrel after insertion of the intra-vaginal ring for all groups
timeFrame: 226-298h
measure: Average concentration (Cav) levonorgestrel after insertion of the intra-vaginal ring for all groups
timeFrame: 226-384h
measure: Average concentration (Cav) levonorgestrel after insertion of the intra-vaginal ring for Tampon group
timeFrame: 466-490h
measure: Average concentration (Cav) levonorgestrel after insertion of the intra-vaginal ring for Tampon group
timeFrame: 490-562h
measure: Average concentration (Cav) levonorgestrel after insertion of the intra-vaginal ring for Tampon group
timeFrame: 490-648h
Secondary outcomes:
measure: Maximum observed plasma concentration before co-medication or tampons (Cmax)
timeFrame: 490h
measure: Time to reach maximum observed concentration before co-medication or tampons (tmax)
timeFrame: 490h
measure: Plasma concentration 28 days after intra-vaginal ring (IVR) insertion (Treatment group D, Day 29) (C(28d))
timeFrame: 672h
measure: Plasma concentration 35 days after IVR insertion (Treatment group D, Day 36)(C(35d))
timeFrame: 840h
measure: Average concentration in the extended wearing period (Treatment D, Days 29-36 using the same IVR)
timeFrame: 672-840h
measure: Terminal half-life associated with the terminal slope after removal of IVR (t1/2)
timeFrame: Up to 6 days after IVR removal
measure: Number of participants with adverse events as a measure of safety and tolerability
timeFrame: Up to 14 days after IVR removal
Other outcomes:
Locations:
city: Berlin
country: Germany
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: