Clinical Study of Vaginal Lactobacilli and Estriol (Gynoflor®) for Atrophic Vaginitis in Breast Cancer Patients

Study Overview
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Brief Summary
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The purpose of this study is to assess the longterm 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.

Official Title
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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

Conditions
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Atrophic Vaginitis

Intervention / Treatment
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* Drug: Gynoflor


Participation Criteria
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Eligibility Criteria
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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 STDs (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 Malignant or pre-cancerous conditions of the uterus, vulva and/or vagina (PAP smear less than 3 years ago) Acute thrombophlebitis, thromboembolic disorders or a history of these disorders in association with previous use of oestrogen preparations Abuse of alcohol or drugs All chronic illnesses which could influence the absorption, distribution, biotransformation or elimination of the test preparation Patient has a condition or is in a situation which, in the investigator's opinion, may put the patient in significant risk, may confound the study result, or may interfere significantly with the patient's participation in the study BMI lower than 18.5 or higher than 30 Patient on steroidal AIs (aromasin) Vulvo-dermatological conditions (like Lichen sclerosus, Lichen rubrus, Psoriasis) Genital prolapses Endometriosis Use of antibiotics or chemotherapeuticals which are harmful to lactobacilli Participation of patient in another investigational drug study, with the exception of treatment optimisation studies with non-steroidal AIs Previous participation in this study Patient is a relative of, or staff directly reporting to the investigator Patient is an employee of the sponsor

Ages Eligible for Study
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Minimum Age: 52 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gynoflor<br>This study consists only of this arm. | Drug: Gynoflor<br>* Vaginal tablet with lyophilised lactobacilli and 0.03 mg estriol; Once daily for 28 days then 3 times per week for 8 weeks;<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum concentrations of estriol (E3), estradiol (E2), estrone (E1) |  | -0.5, 0.5, 1, 2, 3, 4, 6, 8, 24 hours on days 1 and 28 | 
| Calculation of pharmacokinetic parameters: AUC0-24, intraindividual mean, Cmax and tmax |  | on days 1 and 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline / trough serum concentrations of estriol, estradiol, estrone, FSH, LH and SHBG |  | at all visits during 12 weeks | 
| Vaginal pH |  | at all visits during 12 weeks | 
| Clinical symptoms and signs |  | at all visits during 12 weeks | 
| Vaginal maturation index |  | at all visits during 12 weeks except screening | 
| Lactobacillary grade |  | at all visits during 12 weeks except screening | 
| Bacterial vaginosis (BV) score |  | at all visits during 12 weeks except screening | 
| Aerobic vaginitis (AV) score |  | at all visits during 12 weeks except screening | 
| Presence of Candida hyphae or blastospores |  | at all visits during 12 weeks except screening | 
| Global assessment of efficacy |  | visits C1 to C4 during 12 weeks |