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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Medinova AG
- 入组人数
- 16
- 试验地点
- 2
- 主要终点
- Serum Concentrations of Estriol (E3)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 52 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •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
研究组 & 干预措施
Gynoflor
Gynoflor vaginal tablets 1/day x 4 weeks, then 3/week for 8 weeks
干预措施: Estriol 0.03 mg, lyophylized lactobacillus (Drug)
结局指标
主要结局
Serum Concentrations of Estriol (E3)
时间窗: -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
时间窗: Days 0 and 28
Cmax is the highest measured concentration
Calculation of Pharmacokinetic Parameters Estriol: Tmax
时间窗: 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)
时间窗: Days 0 and 28
Area under the curve from administration to the last measured concentration (AUC0-24)
次要结局
- 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)