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

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

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.

Study Overview

• Status: Completed
• Conditions: Atrophic Vaginitis
• Intervention / Treatment: Drug: Gynoflor

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium
    • University Hospital Leuven
• Germany
  • Regensburg, Germany
    • Department of Obstetrics and Gynaecology, University of Regensburg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 52 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 STDs (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 AIs
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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Medinova AG
• Investigators: Principal Investigator: Patrick Neven, Prof. Dr., University Hospital Leuven, Belgium; Principal Investigator: Stefan Buchholz, PD Dr., Department of Obstetrics and Gynaecology, University of Regensburg, Germany; Principal Investigator: Gilbert Donders, Prof. Dr., Femicare, University Hospital, Leuven, Belgium

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: May 10, 2011
• First Submitted That Met QC Criteria: June 8, 2011
• First Posted (Estimate): June 10, 2011

Study Record Updates

• Last Update Posted (Estimate): August 22, 2012
• Last Update Submitted That Met QC Criteria: August 21, 2012
• Last Verified: January 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Vaginal Diseases; Vaginitis; Atrophic Vaginitis; Atrophy
• Other Study ID Numbers: 806109