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

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

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

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13353

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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)	Drug: Anastrozole / Levonorgestrel (BAY98-7196); Release rate of the IVR: 1050 μg/d ATZ + 40 μg/d LNG; Drug: Gyno-Daktarin; 400 mg miconazole nitrate per day for 3 consecutive days
Experimental: Administered Antibiotic; 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); Release rate of the IVR: 1050 μg/d ATZ + 40 μg/d LNG; Drug: Sobelin vaginal creme; 100 mg clindamycin 2-dihydrogen phosphat per day for 3 consecutive days
Experimental: Administered Spermicide; 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); Release rate of the IVR: 1050 μg/d ATZ + 40 μg/d LNG; Drug: Patentex oval; 75 mg Nonoxynol-9 per day for 3 consecutive days
Experimental: Tampons; 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); Release rate of the IVR: 1050 μg/d ATZ + 40 μg/d LNG; Other: Tampon; Other Names: Tampons (3 changes per day) for 3 consecutive days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2015
• Primary Completion (Actual): March 14, 2016
• Study Completion (Actual): July 29, 2016

Study Registration Dates

• First Submitted: September 8, 2015
• First Submitted That Met QC Criteria: September 9, 2015
• First Posted (Estimate): September 10, 2015

Study Record Updates

• Last Update Posted (Actual): July 24, 2017
• Last Update Submitted That Met QC Criteria: July 21, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endometriosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptive Agents, Male; Spermatocidal Agents; Antispermatogenic Agents; Levonorgestrel; Anastrozole; Nonoxynol
• Other Study ID Numbers: 16997; 2014-005167-32 (EudraCT Number)