A Randomized, Open-label Trial to Evaluate the Pharmacokinetics and Pharmacodynamics of 3 Dosages of Estriol After Continuous Vaginal Administration for 21 Days in Healthy, Post-menopausal Women
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Measurement of estriol plasma levels
研究概览
简要总结
This clinical trial evaluated the pharmacokinetics and pharmacodynamics of estriol in healthy post-menopausal women after the application of one vaginal ring containing one of three different dosages of estriol (100 mg (Test 1), 300 mg (Test 2) or 600 mg (Test 3)) with continuous delivery (0.125, 0.250 or 0.500 mg/day) for 21 days. And also, characterized its safety and tolerability.
详细描述
This phase I, single center, open-label, randomised (allocation to treatment), balanced, single dose trial was performed in a parallel-group design. The subjects were randomly assigned to one of the 3 possible treatments (single vaginal application of 1 vaginal ring containing 100, 300 or 600 mg estriol, with delivery rate of 0.125, 0.250 or 0.500 mg/day over 21 days.
Blood samples were collected at 0.5 h prior to drug application, 1, 2, 4, 6, 12, 24, 48, 96, 144, 216, 288, 360, 432 h after application; 5 min prior to removal, i.e., 21 d after application (study day 22), as well as 6, 12 and 24 h after removal to characterise pharmacokinetic parameters of estriol in plasma.
Serum concentrations of follicle stimulating hormone (FSH), luteinising hormone (LH) and sex hormone binding globulin (SHBG) and gynaecological parameters (cytology of vaginal smear, the maturation index and the vaginal pH) were evaluated as pharmacodynamic parameters.
The safety and tolerability was assessed by endometrial thickness and documentation of adverse events.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 45 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Body-mass index (BMI) ≥18.5 kg/m² and ≤ 30.0 kg/m²
- •Postmenopausal state: FSH (plasma) ≥ 40 IU/l, estradiol (serum) ≤ 20 pg/ml last spontaneous menstruation at least 12 months ago
- •Normal transvaginal endometrial scan (endometrial thickness < 5 mm)
- •Good state of health
- •Non-smoker or ex-smoker for at least 6 month
- •Written informed consent, after having been informed about benefits and potential risks of the clinical trial, as well as details of the insurance taken out to cover the subjects participating in the clinical trial
排除标准
- •Existing cardiac, hepatic and/or haematological diseases or pathological findings, which might interfere with the safety or tolerability and/or pharmacokinetics and/or pharmacodynamics of the active ingredient
- •History of relevant central nervous system (CNS) and/or psychiatric disorders and/or currently treated CNS and/or psychiatric disorders
- •Known allergic reactions to the active ingredients used or to constituents of the pharmaceutical preparations
- •Subjects with severe allergies or multiple drug allergies, unless it is judged as not relevant for the clinical trial by the investigator
- •Positive anti-HIV-test (if positive to be verified by western blot), HBs-AG-test (if positive to be verified by test for HBc-IgM) or anti-HCV-test
- •Presence or history of venous or arterial thrombosis (e.g. deep venous thrombosis, pulmonary embolism)
- •Known, past or suspected breast cancer or increased familiar risk for development
- •Known or suspected estrogen-dependent malignant tumours (e.g. endometrial or breast cancer)
- •Undiagnosed genital bleeding
- •Acute vaginal infection or other diseases prohibiting the placement of vaginal ring
- •History of endometrial hyperplasia
- •Migraine or frequent episodes of severe headache
- •History of or current drug or alcohol dependence
- •Subjects who are on a diet which could affect the pharmacokinetics of the active ingredient
- •Regular intake of caffeine containing food or beverages of ≥ 500 mg caffeine per day
- •Blood donation or other blood loss of more than 400 ml within the last 3 months prior to individual enrolment of the subject
- •Participation in a clinical trial during the last 6 months prior to individual enrolment of the subject
- •Concomitant systemic therapy with antibiotics, which might interfere with enterohepatic recirculation (e.g. cephalosporines, neomycin, ampicillin or tetracyclines)
- •Use of sex hormones within 6 months (oral, transdermal, vaginal) or 8 months (intramuscular administered depot preparations used once per month) or 12 months (intramuscular administered depot preparations used once per 3 months) before screening
- •Use of systemic or topical medications or substances which oppose the study objectives or which might influence them within 8 weeks before screening examination
- •Subjects who are unable to understand the written and verbal instructions, in particular regarding the risks and inconveniences they will be exposed to during their participation in the clinical trial
研究组 & 干预措施
Test 1 vaginal ring
Single vaginal application of 1 vaginal ring containing 100 mg estriol, with delivery rate of 0.125 mg/day over 21 days
干预措施: Estriol 0.125 mg/day (Drug)
Test 2 vaginal ring
Single vaginal application of 1 vaginal ring containing 300 mg estriol, with delivery rate of 0.250 mg/day over 21 days
干预措施: Estriol 0.250 mg/day (Drug)
Test 3 vaginal ring
Single vaginal application of 1 vaginal ring containing 600 mg estriol, with delivery rate of 0.500 mg/day over 21 days
干预措施: Estriol 0.500 mg/day (Drug)
结局指标
主要结局
Measurement of estriol plasma levels
时间窗: 0-22 days
Blood sampling for the determination of plasma levels of estriol in participants of each treatment group.
次要结局
- Area Under the Curve (AUC) for estriol(0-22 days)
- Maximum Plasma Concentration (Cmax) of estriol(0-22 days)
- Characterisation of follicle stimulating hormone (FSH)(0-22 days)
- Characterisation of luteinising hormone (LH)(0-22 days)
- Characterisation of sex hormone binding globulin (SHBG)(0-22 days)
- Characterisation of cytology of vaginal smear(0-22 days)
- Calculation of maturation index(0-22 days)
- Determination of vaginal pH(0-22 days)
- Number of adverse events per participant(up to 22days after treatment)
研究者
Gilberto De Nucci
Doctor
Galeno Desenvolvimento de Pesquisas Clínicas