A pharmacokinetics study to determine the blood and uterine tissue concentrations of mifepristone
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- The primary research objective of the current study is to obtain uterine tissue concentrations after 20 days of daily oral treatment with mifepristone at 10 and 25 mg/day.
研究概览
简要总结
This is an exploratory pharmacokinetics study to evaluate the blood and uterine tissue concentrations of mifepristone in women with symptomatic uterine fibroids scheduled for hysterectomy. Mifepristone is a selective progesterone receptor modulator already approved in India for fibroid treatment at oral doses of 5 mg, 10 mg and 25 mg. Local uterine concentrations after oral dosing are not known and this study aims to generate this data to guide future therapeutic approaches including local administration routes.
The primary objective is to measure uterine tissue levels of mifepristone in endometrium myometrium and fibroid tissue after 20 days of daily oral treatment with 10 mg or 25 mg. The secondary objective is to assess systemic plasma concentrations at the same time point.
The design is a single arm open label exploratory tissue distribution study. A total 20 women aged 18 to 50 years scheduled for hysterectomy due to symptomatic fibroids will be enrolled at a single site in India. Patients 1 to 10 will receive 25 mg daily while patients 11 to 20 will receive 10 mg daily for 20 consecutive days before hysterectomy.
Blood samples will be taken before the first dose and 24 hours after the final dose. Uterine tissues including endometrium myometrium and fibroid tissue will be collected during hysterectomy 24 hours after the last dose. All samples will be analyzed using LC MS to determine concentrations.
Inclusion criteria are women aged 18 to 50 years planned for hysterectomy for symptomatic fibroids who are willing to take the study medication and provide samples. Key exclusions include postmenopausal status contraindications to mifepristone abnormal liver or renal function malignant disease unexplained bleeding use of CYP3A modulators or significant alcohol or drug abuse.
The study duration per subject is 20 days of treatment plus the hysterectomy procedure.
The trial will follow Good Clinical Practice and ISO 14155 2020 guidelines. Risks are minimal as hysterectomy and mifepristone treatment are part of routine care. Additional risk is limited to blood sampling.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 50.00 Year(s)（—）
- 性别
- Female
入选标准
- •Planned hysterectomy for one or more symptomatic fibroids
- •Age 18 to 50 years
- •Is willing to participate in study and consented for the same
- •Is willing to take daily oral treatment of 10 mg or 25 mg mifepristone during 20 days before hysterectomy
- •Is willing to give blood sample before starting Mifepristone and after completing 20 doses.
排除标准
- •Medical History
- •Post menopausal
- •Any contraindication to hysterectomy
- •Uterus larger than a sixteen weeks gestation uterus as measured by pelvic manual examination
- •Abnormal liver and renal function
- •History of relevant known or suspected malignant tumors.
- •History of unexplained vaginal bleeding or endometrial hyperplasia with atypia or endometrial carcinoma
- •Contraindication to mifepristone, including: adrenal disease; sickle cell anemia; severe liver, respiratory, or renal disease; and blood clotting defect.
- •History of allergy to Mifepristone Prior or concomitant medication
- •CYP3A inhibitors (itraconazole, voriconazole, clarithromycin, erythromycin) or inducers (barbiturates, carbamazepine, nevirapine, phenytoin, primidone, rifabutin, rifampicin, ritonavir, herbals containing hypericum perforatum) as well as consumption of grapefruit and derivatives (juices etc…).
- •Participation in clinical studies of drugs in the past 3 months Other
- •Inability to establish a venous catheter for blood sampling.
- •Regular consumption of more than 10 g of alcohol per day or anamnestic information about alcoholism, drug addiction, drug abuse.
结局指标
主要结局
The primary research objective of the current study is to obtain uterine tissue concentrations after 20 days of daily oral treatment with mifepristone at 10 and 25 mg/day.
时间窗: Mifepristone tissue concentrations at trough levels after 20 days of daily treatment in endometrium, myometrium and fibroid tissue
次要结局
- A secondary objective is to obtain the corresponding systemic concentrations(Plasma concentrations of mifepristone at trough levels after 20 days of daily treatment)
研究者
Dr Smriti Gupta
Subharti Medical College