A Clinical Study of Pharmacokinetics, Efficacy and Safety of Vaginal Application of Lyophilised Lactobacilli and 0.03 mg Estriol (Gynoflor®) on Atrophic Vaginitis in Postmenopausal Breast Cancer Patients Treated With Aromatase Inhibitors
Overview
- Phase
- Phase 1
- Intervention
- Estriol 0.03 mg, lyophylized lactobacillus
- Conditions
- Atrophic Vaginitis
- Sponsor
- Medinova AG
- Enrollment
- 16
- Locations
- 2
- Primary Endpoint
- Serum Concentrations of Estriol (E3)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
The purpose of this study is to assess the long term safety and efficacy of the vaginal application of Gynoflor®, an extremely low dosed estrogen therapy with lactobacilli, on atrophic vaginitis in postmenopausal breast cancer patients who have been treated with aromatase inhibitors.
Detailed Description
Two center phase I pharmacokinetic study assessed circulating estrogens in breast cancer patients on a non-steroidal aromatase inhibitor (NSAI) with vaginal atrophy using vaginal ultra-low-dose 0.03 mg estriol (E3) and Lactobacillus combination vaginal tablets (Gynoflor). 16 women on nonsteroidal aromatase inhibitor with severe vaginal atrophy applied a daily vaginal tablet of Gynoflor for 28 days followed by a maintenance therapy of 3 tablets weekly for 8 weeks.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients with breast cancer on non-steroidal AI therapy (AI therapy start at least 6 months ago, and are scheduled to receive them during the study)
- •Postmenopausal and age ≥52 with cessation of menses for at least 12 months
- •Age 52 - 75 years
- •Clinical symptoms of vaginal atrophy
- •Vaginal pH \> 5.0
- •Karnofsky score ≥80%
- •Signed Informed Consent Form together with contractual capability
Exclusion Criteria
- •Local or systemic use of any other sexual hormones (estrogens, progestins, androgens), 6 months before and during study
- •Local or systemic use of phytoestrogens or products known for or taken to improve vaginal mucosal function, risk of vaginal infections, or vulvovaginal symptoms, 4 weeks before and during study
- •Local or systemic use of any other anti-infectives, 2 weeks before and during study
- •Use of any other vaginal medication, vaginal rinses and/or moisturizers, gels containing xylocain or other analgesic products to decrease pain during intercourse, 1 week before and during study
- •Known or suspected hypersensitivity or intolerance to the study medications, inclusive their excipients
- •Suspicion of or clinically manifest sexually transmitted infections (infections with Neisseria gonorrhoea, Chlamydia trachomatis, Treponema pallidum, genital herpes, Trichomonas vaginalis, genital condylomata, HIV)
- •Clinical evidence of vaginal infections requiring extra treatment
- •Any infections of the upper genital tract
- •Hysterectomy
- •Genital haemorrhage of unknown origin
Arms & Interventions
Gynoflor
Gynoflor vaginal tablets 1/day x 4 weeks, then 3/week for 8 weeks
Intervention: Estriol 0.03 mg, lyophylized lactobacillus
Outcomes
Primary Outcomes
Serum Concentrations of Estriol (E3)
Time Frame: -0.5, 0.5, 1, 2, 3, 4, 6, 8, 24 hours on days 0 and 28
Estrogens were analyzed using a highly sensitive gas chromatography-mass spectrometry (GC/MS) method. The lower limits of quantitation (LLOQ) were 10.00 pg/ml for E3, 1.The coefficient of variation (CV, intra-assay variation) was 2.0 % for E3 (calibration range (CR) 10.00-500.00 pg/). The lower limits of quantitation (LLOQ) were 1.00 pg/ml for E2, and 2.00 pg/ml for E1.The coefficient of variation (CV, intra-assay variation) was 4.2 % for E2 (CR 1.00-150.00 pg/ml), and 3.4 % for E1 (CR 2.00-300.00 pg/ml).
Calculation of Pharmacokinetic Parameters Estriol: Cmax
Time Frame: Days 0 and 28
Cmax is the highest measured concentration
Calculation of Pharmacokinetic Parameters Estriol: Tmax
Time Frame: Days 0 and 28
Tmax is the peak time at which the Cmax (maximum concentration) was measured
Calculation of Pharmacokinetic Parameters Estriol: Area Under the Curve (AUC)
Time Frame: Days 0 and 28
Area under the curve from administration to the last measured concentration (AUC0-24)
Secondary Outcomes
- Baseline / Trough Serum Concentrations of Estriol(Days 0, 14, 28, 56 and 84)
- Vaginal pH(at all visits during 12 weeks)
- Baseline / Trough Serum Concentrations of Luteinizing Hormone (LH)(Days 0, 14, 28, 56 and 84)
- Baseline / Trough Serum Concentrations of Sex Hormone Binding Globulin (SHBG)(Days 0, 14, 28, 56 and 84)
- Baseline / Trough Serum Concentrations of Follicule Stimulating Hormone (FSH)(Days 0, 14, 28, 56 and 84)