Atrophic VaginitisPhase 1GynoflorNCT01370551

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

A Phase 1 study testing Estriol 0.03 mg, lyophylized lactobacillus in people with Atrophic Vaginitis, run by Medinova AG at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 52 to 75 years, women only
Conditions the study is for: Atrophic Vaginitis
What is being tested?: Estriol 0.03 mg, lyophylized lactobacillus
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 16 participants
Where: 2 sitesin 2 countries
Study dates: Apr 2011to Jul 2012
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 52 to 75 years
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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)

Show all 25Show fewer

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 aromatase inhibitors (AI)s
Previous participation in this study
Patient is a relative of, or staff directly reporting to the investigator
Patient is an employee of the sponsor

Trial locations and contacts

2 sites in 2 countries.

Country

City, postcode or hospital

2 sites in 2 countries

Belgium1 site

University Hospital Leuven
Leuven

Other trials in Belgium

Germany1 site

Department of Obstetrics and Gynaecology, University of Regensburg
Regensburg

Other trials in Germany

About this study

Official title: 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

Read the 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.

Conditions: Atrophic Vaginitis
Being tested: Estriol 0.03 mg, lyophylized lactobacillus
Medical subject headings: Atrophic Vaginitis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Estriol 0.03 mg, lyophylized lactobacillusDrug
Also called Gynoflor
Vaginal tablet with lyophilised lactobacilli and 0.03 mg estriol; Once daily for 28 days then 3 times per week for 8 weeks;

Study groups in NCT01370551
Study group	Role	What they receive
Gynoflor	Experimental	Gynoflor vaginal tablets 1/day x 4 weeks, then 3/week for 8 weeks Receives: Drug: Estriol 0.03 mg, lyophylized lactobacillus

What is being measured

The primary outcome is the main question the study is designed to answer.

Serum Concentrations of Estriol (E3)
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).
Measured: -0.5, 0.5, 1, 2, 3, 4, 6, 8, 24 hours on days 0 and 28
Calculation of Pharmacokinetic Parameters Estriol: Cmax
Cmax is the highest measured concentration
Measured: Days 0 and 28
Calculation of Pharmacokinetic Parameters Estriol: Tmax
Tmax is the peak time at which the Cmax (maximum concentration) was measured
Measured: Days 0 and 28
Calculation of Pharmacokinetic Parameters Estriol: Area Under the Curve (AUC)
Area under the curve from administration to the last measured concentration (AUC0-24)
Measured: Days 0 and 28

Secondary outcomes (5)

Baseline / Trough Serum Concentrations of Estriol
Measured: Days 0, 14, 28, 56 and 84
Vaginal pH
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.
Measured: at all visits during 12 weeks
Baseline / Trough Serum Concentrations of Luteinizing Hormone (LH)
Measured: Days 0, 14, 28, 56 and 84
Baseline / Trough Serum Concentrations of Sex Hormone Binding Globulin (SHBG)
Measured: Days 0, 14, 28, 56 and 84
Baseline / Trough Serum Concentrations of Follicule Stimulating Hormone (FSH)
Measured: Days 0, 14, 28, 56 and 84

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 2011Jul 2012

First posted10 Jun 2011 (estimated)
Study startApr 2011
Primary completionJul 2012
Study completionJul 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Atrophic VaginitisStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 16 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01370551
Sponsor's protocol ID: 806109
Acronym: Gynoflor
Status last verified: Oct 2024
First submitted: 10 May 2011
Last updated: 15 Oct 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Donders G, Neven P, Moegele M, Lintermans A, Bellen G, Prasauskas V, Grob P, Ortmann O, Buchholz S. Ultra-low-dose estriol and Lactobacillus acidophilus vaginal tablets (Gynoflor((R))) for vaginal atrophy in postmenopausal breast cancer patients on aromatase inhibitors: pharmacokinetic, safety, and efficacy phase I clinical study. Breast Cancer Res Treat. 2014 Jun;145(2):371-9. doi: 10.1007/s10549-014-2930-x. Epub 2014 Apr 10.
PubMed 24718774
Buchholz S, Mogele M, Lintermans A, Bellen G, Prasauskas V, Ortmann O, Grob P, Neven P, Donders G. Vaginal estriol-lactobacilli combination and quality of life in endocrine-treated breast cancer. Climacteric. 2015 Apr;18(2):252-9. doi: 10.3109/13697137.2014.991301. Epub 2015 Jan 20.
PubMed 25427450
Donders G, Bellen G, Neven P, Grob P, Prasauskas V, Buchholz S, Ortmann O. Effect of ultra-low-dose estriol and lactobacilli vaginal tablets (Gynoflor(R)) on inflammatory and infectious markers of the vaginal ecosystem in postmenopausal women with breast cancer on aromatase inhibitors. Eur J Clin Microbiol Infect Dis. 2015 Oct;34(10):2023-8. doi: 10.1007/s10096-015-2447-1. Epub 2015 Jul 30.
PubMed 26223323

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Recruiting
F-GYN for Vaginal Dryness and Vulvovaginal Atrophy
Atrophic Vaginitis, Atrophic Vulvovaginitis
Not yet recruitingPhase 4
Vaginal Estradiol vs Moisturizer to Improve Postmenopausal Vaginal Aging Symptoms and the Microbiome in Women Living With HIV
Menopausal Complaints, Vaginal Atrophy
Recruiting
VALOR: Vaginal Atrophy & Long-term Observation of Recovery
Atrophic Vaginitis, Vaginal Atrophy
Active, not recruiting
LASER and Radiofrequency and Genitourinary Syndrome of Menopause
Postmenopausal Atrophic Vaginitis, Postmenopausal Symptoms
Not yet recruitingPhase 4
Difference in Serum Estrogen Level Based on Methods of Vaginal Estrogen Application (fingertip Vs Applicator Use) in Post-menopausal Women
Postmenopausal Atrophic Vaginitis, Genitourinary Syndrome of Menopause

All Atrophic Vaginitis trials

Study at a glance

From the registry record, last updated by the sponsor on 15 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT01370551
Acronym / sponsor ID: Gynoflor / 806109
Conditions: Atrophic Vaginitis
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 16 participants (actual)
Lead sponsor: Medinova AGIndustry (pharma, biotech, devices)
Study start: Apr 2011
Primary completion: Jul 2012 (actual)
Study completion: Jul 2012 (actual)
First posted: 10 Jun 2011 (estimated)
Results: Posted 15 Oct 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Gynoflor	Experimental	Drug: Estriol 0.03 mg, lyophylized lactobacillusGynoflor vaginal tablets 1/day x 4 weeks, then 3/week for 8 weeks

Who may qualify

Ages: 52 to 75 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

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

Key exclusion criteria (25 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Estriol 0.03 mg, lyophylized lactobacillusAlso: GynoflorVaginal tablet with lyophilised lactobacilli and 0.03 mg estriol; Once daily for 28 days then 3 times per week for 8 weeks;	Drug	Gynoflor

Primary outcome

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)

5 secondary outcomes

Baseline / Trough Serum Concentrations of Estriol
Time frame: Days 0, 14, 28, 56 and 84
Vaginal pH
Time frame: at all visits during 12 weeks
Baseline / Trough Serum Concentrations of Luteinizing Hormone (LH)
Time frame: Days 0, 14, 28, 56 and 84
Baseline / Trough Serum Concentrations of Sex Hormone Binding Globulin (SHBG)
Time frame: Days 0, 14, 28, 56 and 84
Baseline / Trough Serum Concentrations of Follicule Stimulating Hormone (FSH)
Time frame: Days 0, 14, 28, 56 and 84

Results and safety

Results posted to the registry on 15 Oct 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Gynoflor	16	16

Primary outcome: Serum Concentrations of Estriol (E3)

Time frame: -0.5, 0.5, 1, 2, 3, 4, 6, 8, 24 hours on days 0 and 28. Mean (Full Range). Unit: pg/ml

Measure	Gynoflor n = 16
-0.5 h (Day 0)	0 (0 to 0)
-0.5 h (Day 28)	0.91 (0 to 14.5)
0.5 h (Day 0)	3.83 (0 to 14.10)
0.5 h (Day 28)	1.58 (0 to 12.90)
1 h (Day 0)	11.04 (0 to 18.8)
1 h (Day 28)	1.55 (0 to 14.40)
2 h (Day 0)	72.73 (0 to 168)
2 h (Day 28)	1.96 (0.00 to 16.60)

Primary outcome: Calculation of Pharmacokinetic Parameters Estriol: Cmax

Time frame: Days 0 and 28. Mean (Standard Deviation). Unit: pg/ml

Measure	Gynoflor n = 16
Cmax (Day 0)	104.5 (40.9)
Cmax (Day 28)	15.8 (13.9)

Primary outcome: Calculation of Pharmacokinetic Parameters Estriol: Tmax

Time frame: Days 0 and 28. Mean (Standard Deviation). Unit: hours

Measure	Gynoflor n = 16
Tmax (Day 0)	2.5 (0.5)
Tmax (Day 28)	7.2 (1.5)

Primary outcome: Calculation of Pharmacokinetic Parameters Estriol: Area Under the Curve (AUC)

Time frame: Days 0 and 28. Mean (Standard Deviation). Unit: hours * pg/ml

Measure	Gynoflor n = 16
AUC (0-24h) (Day 0)	212 (93.2)
AUC (0-24h) (Day 28)	130.7 (147.2)

Population analysed: PP

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: 12 weeks. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Gynoflor	0 of 16 (0%)	14 of 16 (87.5%)	0 of 16

Limitations and caveats (from the sponsor): The weaknesses of the study were small numbers for testing of some parameters (especially dyspareunia).

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 24718774Donders G, Neven P, Moegele M, Lintermans A, Bellen G, Prasauskas V, Grob P, Ortmann O, Buchholz S. Ultra-low-dose estriol and Lactobacillus acidophilus vaginal tablets (Gynoflor((R))) for vaginal atrophy in postmenopausal breast cancer patients on aromatase inhibitors: pharmacokinetic, safety, and efficacy phase I clinical study. Breast Cancer Res Treat. 2014 Jun;145(2):371-9. doi: 10.1007/s10549-014-2930-x. Epub 2014 Apr 10.
Results publication: PubMed 25427450Buchholz S, Mogele M, Lintermans A, Bellen G, Prasauskas V, Ortmann O, Grob P, Neven P, Donders G. Vaginal estriol-lactobacilli combination and quality of life in endocrine-treated breast cancer. Climacteric. 2015 Apr;18(2):252-9. doi: 10.3109/13697137.2014.991301. Epub 2015 Jan 20.
Results publication: PubMed 26223323Donders G, Bellen G, Neven P, Grob P, Prasauskas V, Buchholz S, Ortmann O. Effect of ultra-low-dose estriol and lactobacilli vaginal tablets (Gynoflor(R)) on inflammatory and infectious markers of the vaginal ecosystem in postmenopausal women with breast cancer on aromatase inhibitors. Eur J Clin Microbiol Infect Dis. 2015 Oct;34(10):2023-8. doi: 10.1007/s10096-015-2447-1. Epub 2015 Jul 30.
Publication of main resultsLink provided by the sponsor.

Related trials for Atrophic Vaginitis

Recruiting
F-GYN for Vaginal Dryness and Vulvovaginal Atrophy
Atrophic Vaginitis, Atrophic Vulvovaginitis
Not yet recruitingPhase 4
Vaginal Estradiol vs Moisturizer to Improve Postmenopausal Vaginal Aging Symptoms and the Microbiome in Women Living With HIV
Menopausal Complaints, Vaginal Atrophy
Recruiting
VALOR: Vaginal Atrophy & Long-term Observation of Recovery
Atrophic Vaginitis, Vaginal Atrophy
Active, not recruiting
LASER and Radiofrequency and Genitourinary Syndrome of Menopause
Postmenopausal Atrophic Vaginitis, Postmenopausal Symptoms
Not yet recruitingPhase 4
Difference in Serum Estrogen Level Based on Methods of Vaginal Estrogen Application (fingertip Vs Applicator Use) in Post-menopausal Women
Postmenopausal Atrophic Vaginitis, Genitourinary Syndrome of Menopause

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Patrick Neven, Prof. Dr. principal investigator

University Hospital Leuven, Belgium

Stefan Buchholz, PD Dr. principal investigator

Department of Obstetrics and Gynaecology, University of Regensburg, Germany

Gilbert Donders, Prof. Dr. principal investigator

Femicare, University Hospital, Leuven, Belgium

2 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Estriol 0.03 mg, lyophylized lactobacillus in people with Atrophic Vaginitis, run by Medinova AG at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Belgium, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Serum Concentrations of Estriol (E3) (time frame: -0.5, 0.5, 1, 2, 3, 4, 6, 8, 24 hours on days 0 and 28). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01370551, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2024.