Prospective, Randomized, Open-label and Comparative Study to Determine the Pharmacokinetic Parameters of Vaginal Rings That Contain DHEA, Testosterone, or the Combination of Both Androgens, in Comparison With Oral Administration of DHEA and Transdermal Administration of Testosterone, in Postmenopausal Women
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 46
- 试验地点
- 1
- 主要终点
- Testosterone: Area under the serum concentration time curve (AUC0-72)
研究概览
简要总结
This study was performed to determine the pharmacokinetic parameters of vaginal rings that contain DHEA, testosterone, or combinations of both androgens, in comparison to the oral administration of DHEA and the transdermal administration of testosterone.
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
- None
入排标准
- 年龄范围
- 40 Years 至 60 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Women between 40 to 60 years old.
- •Postmenopausal with spontaneous amenorrhea of 1 year or more, regardless of follicle stimulating hormone (FSH) levels; or amenorrhea of 6 to 12 months, in which the postmenopausal state will be confirmed with a FSH level of 0.040 international units per milliliter or higher.
- •Body Mass Index between 19 and
- •Intact uterus.
- •Not having received hormone therapy in the month prior to selection.
- •Adequate veins to conduct serial blood samplings.
- •Recent Pap smear (not more than 12 months), with a result negative for malignant neoplastic cells, and that contains sufficient endocervical cells for analysis. If the Pap smear was performed more than 12 months ago or cannot be verified through clinical documentation, it must be repeated during the selection process.
- •Normal mammogram, BI.RADS I or II (American College of Radiology), within the last year. If the mammogram was performed more than 12 months ago or cannot be verified through clinical documentation, it must be repeated during the selection process.
- •That provide written informed consent.
排除标准
- •Use at randomization of phenytoin, barbiturates, primidone, carbamazepine, rifampin, griseofulvin, ketoconazole, lipid-lowering agents.
- •History of diseases such as coronary heart disease, breast cancer, uterine cancer, and/or chronic hepatic disease.
- •Unconscious volunteers, severely ill, or with mental disability.
- •Allergy and hypersensitivity to DHEA and/or testosterone.
- •Untreated or uncontrolled hypertension, with systolic pressure above 140 mm Hg or diastolic pressure above 90 mm Hg.
- •Current participation in other research at the moment of the screening visit, or having concluded their participation in a previous research in less than 30 days since their last visit.
- •Pregnant or lactating women; pregnancy must be confirmed with a urine positive human chorionic gonadotropin (HCG) test during screening.
- •History of vein thrombosis (deep vein thrombosis, pulmonary embolism).
- •History of arterial thrombosis (myocardial infarction) or prodromic conditions (e.g. transient ischemic attack, angina pectoris).
- •History of stroke.
- •History of migraine with focal neurological manifestations.
- •History of hepatic tumor (benign or malignant).
- •History of clinical atherosclerosis in first grade relatives (parents, siblings, sons [men less than 55 years old and women less than 65 years old]).
- •Smoking (5 or more cigarettes a day).
- •Diabetes mellitus that will be ruled out at screening if fasting glucose is less than 100 mg/dL or between 100 and 125 mg/dL, with Oral Glucose Tolerance Test that rules out diabetes. Diabetes will be confirmed with blood glucose equal to or above 200 mg/dL or 2 fasting glucose tests equal to or above 126 mg/dL.
- •High density lipopolysaccharide (HDL)-cholesterol below 35 mg/dL.
研究组 & 干预措施
Group 1: AVD
Vaginal ring with 2.2 grams dehydroepiandrosterone (DHEA), wearing time 72 hours
干预措施: Dehydroepiandrosterone 2.2 g (Drug)
Group 2: AVT
Vaginal ring with 35 mg testosterone, wearing time 72 hours.
干预措施: Testosterone (Drug)
Group 3: AVD+T
Vaginal ring with 1.5 grams DHEA and 25 mg testosterone, wearing time 72 hours.
干预措施: Dehydroepiandrosterone 1.5 g/Testosterone 25 mg (Drug)
Group 4: DHEA capsule
Capsules with 25 mg DHEA, oral administration every 8 hours for a 72-hour period.
干预措施: Dehydroepiandrosterone Oral Capsule (Drug)
Group 5: Testosterone transdermal gel
Testosterone transdermal gel with dosing valve (pump): administration of 3 pump actuations (equivalent to 5 mg of testosterone each) per day (total daily dose 15 mg), on 3 consecutive days (72 hours).
干预措施: Testosterone Topical Gel (Drug)
结局指标
主要结局
Testosterone: Area under the serum concentration time curve (AUC0-72)
时间窗: Pre-dose and from 30 minutes after administration of the assigned treatment to 72 hours
Serum testosterone was measured pre-dose and at 30 minutes, at 1 hour, 2, 4, 6, 8, 24, 48, and 72 hours after vaginal ring insertion, the transdermal application of the testosterone gel, or after taking DHEA capsules. The AUC0-72 was calculated.
DHEA: Maximum serum concentration (Cmax)
时间窗: Pre-dose and from 30 minutes after administration of the assigned treatment to 72 hours
Serum DHEA was measured pre-dose and at 30 minutes, at 1 hour, 2, 4, 6, 8, 24, 48, and 72 hours after vaginal ring insertion, the transdermal application of the testosterone gel, or after taking DHEA capsules. Cmax was calculated.
DHEA: Area under the serum concentration time curve (AUC0-72)
时间窗: Pre-dose and from 30 minutes after administration of the assigned treatment to 72 hours
Serum DHEA were measured pre-dose and at 30 minutes, at 1 hour, 2, 4, 6, 8, 24, 48, and 72 hours after vaginal ring insertion, the transdermal application of the testosterone gel, or after taking DHEA capsules. The AUC0-72 was calculated.
DHEA: Time to achieve maximum serum concentration (tmax)
时间窗: pre-dose and from 30 minutes after administration of the assigned treatment to 72 hours
Serum DHEA was measured pre-dose and at 30 minutes, at 1 hour, 2, 4, 6, 8, 24, 48, and 72 hours after vaginal ring insertion, the transdermal application of the testosterone gel, or after taking DHEA capsules. Tmax was calculated.
Testosterone: Average serum concentration 0-24 hours
时间窗: Pre-dose and from 30 minutes after administration of the assigned treatment to 24 hours
Serum testosterone was measured pre-dose and at 30 minutes, at 1 hour, 2, 4, 6, 8, 24, 48, and 72 hours after vaginal ring insertion, the transdermal application of the testosterone gel, or after taking DHEA capsules. The average serum concentration achieved in the first 24 hours after administration of the assigned treatment was calculated.
Testosterone: Maximum serum concentration (Cmax)
时间窗: Pre-dose and from 30 minutes after administration of the assigned treatment to 72 hours
Serum testosterone was measured pre-dose and at 30 minutes, at 1 hour, 2, 4, 6, 8, 24, 48, and 72 hours after vaginal ring insertion, the transdermal application of the testosterone gel, or after taking DHEA capsules. Cmax was calculated.
Testosterone: Time to achieve maximum serum concentration (tmax)
时间窗: pre-dose and from 30 minutes after administration of the assigned treatment to 72 hours
Serum testosterone was measured pre-dose and at 30 minutes, at 1 hour, 2, 4, 6, 8, 24, 48, and 72 hours after vaginal ring insertion, the transdermal application of the testosterone gel, or after taking DHEA capsules. Tmax was calculated.
DHEA: Average serum concentration 0-24 hours
时间窗: Pre-dose and from 30 minutes after administration of the assigned treatment to 24 hours
Serum DHEA was measured pre-dose and at 30 minutes, at 1 hour, 2, 4, 6, 8, 24, 48, and 72 hours after vaginal ring insertion, the transdermal application of the testosterone gel, or after taking DHEA capsules. The average serum concentration achieved in the first 24 hours after administration of the assigned treatment was calculated.
次要结局
未报告次要终点