Dose-response Study With Three Vaginal Rings With Different Doses of Estriol and Trimegestone: Effect on Progesterone and Estradiol Levels in Healthy Females With Childbearing Potential
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Measurement of E2 and PG plasma levels
研究概览
简要总结
This clinical trial is performed as proof of pharmacological action investigation by demonstration of ovulation inhibition (dose-response study) under treatment with three Test vaginal rings releasing varying doses of estriol (E3) and trimegestone (TMG).
Blood samples for determination of estradiol (E2) and progesterone (PG) levels will serve as pharmacodynamic surrogate parameters for characterization of the treatment effect on the endogenous hormones.
Blood samples for determination of E3 and TMG in plasma will be collected in order to characterize pharmacokinetic parameters.
Additionally, local tolerability characterized by gynecological inspection of the vaginal mucosa prior to and after insertion of the Investigational Medicinal Product (IMPs) is planned to be assessed
详细描述
The IMPs, releasing either 0.400 mg E3 and 0.06 mg TMG, or 0.300 mg E3 and 0.12 mg TMG, or 0.200 mg E3 and 0.18 mg TMG per 24 h, will be applied intravaginally and remain in the vagina for the subsequent 21 days (single dose, 1 treatment cycle). A total of 36 female subjects, 12 per treatment group, are intended to be randomized.
Blood samples for determination of E2 and PG levels will be collected during treatment and until 20 days after removal of the ring. Blood samples for determination of E3 and TMG in plasma will be collected over the treatment period and until 48 h after removal of the ring.
Bleeding intensity will also be documented during treatment and until 20 days after removal of the vaginal ring in a diary to characterize the effects of the different treatments.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Under treatment with a commercially available combined oral contraceptive containing 30 µg ethinylestradiol (EE) and 150 µg levonorgestrel (LVN) for the last 3 months prior to enrolment
- •Body-mass index (BMI): ≥ 18.5 kg/m² and ≤ 30.0 kg/m²
- •Good state of health
- •Non-smoker, ex-smoker for at least 3 months
- •Regular menstrual cycle with a length between 21 and 35 days
- •Written informed consent, after having been informed about benefits and potential risks of the clinical trial
排除标准
- •Existing diseases or pathological findings, which might interfere with the safety or tolerability, and/or pharmacokinetics of the IMPs
- •Subjects with severe allergies or multiple drug allergies
- •Positive anti human immunodeficiency virus (anti-HIV) test, hepatitis B surface antigen (HBs-AG) test or anti hepatitis C virus (anti-HCV) test
- •Presence or history of venous or arterial thrombosis, cerebrovascular accident, or increased risk of thrombosis
- •Diabetes mellitus
- •Unclarified vaginal bleeding or frequent infections of the urogenital tract
- •Severe or chronic constipation
- •Presence or history of migraine
- •Drug or alcohol dependence
- •Blood donation or other blood loss of more than 400 ml within the last 3 months
- •Participation in a clinical trial during the last 6 months
- •Pregnant or lactating women
- •Subjects who do not agree to apply a barrier method for contraception
研究组 & 干预措施
Test 1 vaginal ring
Single intravaginal application of 1 vaginal ring of Estriol 0.400 mg/day and Trimegestone 0.06 mg/day (Test 1) over 21 days
干预措施: Estriol 0.400 mg/day and Trimegestone 0.06 mg/day (Drug)
Test 2 vaginal ring
Single intravaginal application of 1 vaginal ring of Estriol 0.300 mg/day and Trimegestone 0.12 mg/day (Test 2) over 21 days
干预措施: Estriol 0.300 mg/day and Trimegestone 0.12 mg/day (Drug)
Test 3 vaginal ring
Single intravaginal application of 1 vaginal ring of Estriol 0.200 mg/day and Trimegestone 0.18 mg/day (Test 3) over 21 days
干预措施: Estriol 0.200 mg/day and Trimegestone 0.18 mg/day (Drug)
结局指标
主要结局
Measurement of E2 and PG plasma levels
时间窗: 0 - 41 days
Blood sampling for the determination of plasma levels of E2 and PG, in participants of each treatment group, as surrogate variables for treatment response.
Measurement of E3 and TMG plasma levels
时间窗: 0 - 23 days
Blood sampling for the determination of plasma levels of E3 and TMG, in participants of each treatment group.
次要结局
- Bleeding intensity(start of treatment until 42 days after treatment)
- Number of adverse events per participant(up to 42 days after treatment)
- Maximum Plasma Concentration (Cmax) of E3 and TMG(0 - 23 days)
- Area Under the Curve (AUC) for E3 and TMG(0 - 23 days)
研究者
Gilberto De Nucci
Director
Galeno Desenvolvimento de Pesquisas Clínicas