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

Phase 1

Completed

• Conditions: Atrophic Vaginitis
• Interventions: Drug: Estriol 0.03 mg, lyophylized lactobacillus

• Registration Number: NCT01370551
• Lead Sponsor: Medinova AG

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.

Study Timeline

• Study Start: 2011-04
• Study First Submitted: 2011-05-10
• Study First Submitted QC: 2011-06-08
• Study First Posted: 2011-06-10
• Primary Completion: 2012-07
• Study Completion: 2012-07
• Results First Submitted: 2023-03-15
• Status Verified: 2024-10
• Results First Submitted QC: 2024-10-10
• Last Update Submitted: 2024-10-10
• Results First Posted: 2024-10-11
• Last Update Posted: 2024-10-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 16

Inclusion Criteria

1. 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)
2. Postmenopausal and age ≥52 with cessation of menses for at least 12 months
3. Age 52 - 75 years
4. Clinical symptoms of vaginal atrophy
5. Vaginal pH > 5.0
6. Karnofsky score ≥80%
7. Signed Informed Consent Form together with contractual capability

Exclusion Criteria

1. Local or systemic use of any other sexual hormones (estrogens, progestins, androgens), 6 months before and during study
2. 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
3. Local or systemic use of any other anti-infectives, 2 weeks before and during study
4. 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
5. Known or suspected hypersensitivity or intolerance to the study medications, inclusive their excipients
6. Suspicion of or clinically manifest sexually transmitted infections (infections with Neisseria gonorrhoea, Chlamydia trachomatis, Treponema pallidum, genital herpes, Trichomonas vaginalis, genital condylomata, HIV)
7. Clinical evidence of vaginal infections requiring extra treatment
8. Any infections of the upper genital tract
9. Hysterectomy
10. Genital haemorrhage of unknown origin
11. Malignant or pre-cancerous conditions of the uterus, vulva and/or vagina (PAP smear less than 3 years ago)
12. Acute thrombophlebitis, thromboembolic disorders or a history of these disorders in association with previous use of oestrogen preparations
13. Abuse of alcohol or drugs
14. All chronic illnesses which could influence the absorption, distribution, biotransformation or elimination of the test preparation
15. 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
16. BMI lower than 18.5 or higher than 30
17. Patient on steroidal AIs (aromasin)
18. Vulvo-dermatological conditions (like Lichen sclerosus, Lichen rubrus, Psoriasis)
19. Genital prolapses
20. Endometriosis
21. Use of antibiotics or chemotherapeuticals which are harmful to lactobacilli
22. Participation of patient in another investigational drug study, with the exception of treatment optimisation studies with non-steroidal aromatase inhibitors (AI)s
23. Previous participation in this study
24. Patient is a relative of, or staff directly reporting to the investigator
25. Patient is an employee of the sponsor

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Gynoflor	Estriol 0.03 mg, lyophylized lactobacillus	Gynoflor vaginal tablets 1/day x 4 weeks, then 3/week for 8 weeks

Primary Outcome Measures

Name	Time	Method
Serum Concentrations of Estriol (E3)	-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	Days 0 and 28	Cmax is the highest measured concentration
Calculation of Pharmacokinetic Parameters Estriol: Tmax	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)	Days 0 and 28	Area under the curve from administration to the last measured concentration (AUC0-24)

Secondary Outcome Measures

Name	Time	Method
Baseline / Trough Serum Concentrations of Estriol	Days 0, 14, 28, 56 and 84
Vaginal pH	at all visits during 12 weeks	The normal vaginal pH is 3.8-5.0 pH is a logarithmic scale used to specify the acidity or basicity of aqueous solutions. The scale has values ranging from zero (the most acidic) to 14 (the most basic). Pure water has a pH value of 7. This value is considered neutral-neither acidic or basic.
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

Trial Locations

Locations (2)

Department of Obstetrics and Gynaecology, University of Regensburg; 🇩🇪 Regensburg, Germany

University Hospital Leuven; 🇧🇪 Leuven, Belgium