A MULTI-CENTER, RANDOMIZED STUDY TO EVALUATE THE PHARMACOKINETIC AND PHARMACODYNAMIC PROFILE, CONTRACEPTIVE EFFICACY AND SAFETY OF DAILY ORAL LOW DOSE ULIPRISTAL ACETATE

一项多中心、随机研究，评估每日口服低剂量醋酸乌利司他的药代动力学和药效学特征、避孕功效和安全性

• 批准号: 10078911
• 负责人: STEPHANIE TEAL
• 金额: $ 16.74万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-16 至 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10078911
• 关键词: Acetates; Adherence; Age; Amenorrhea; Clinical Trials; Clinical Trials Network; Contraceptive Agents; Contraceptive methods; Dose; Estrogens; Hemorrhage; In Vitro; Interruption; Menstrual cycle; Methods; Mission; National Institute of Child Health and Human Development; Non obese; Obesity; Oral; Oral Contraceptives; Ovulation; Pattern; Population; Progesterone Receptors; Progestins; Public Health; Randomized; Regimen; Risk; Safety; Time; United States Food and Drug Administration; Uterine Fibroids; Woman; arm; contraceptive efficacy; emergency contraception; malignant breast neoplasm; pharmacokinetics and pharmacodynamics; pill; progesterone receptor A; reproductive; side effect; treatment arm; venous thromboembolism

There is a demand for estrogen-free contraception in order to reduce the risk of venous thromboembolism (VTE), particularly for obese women. A new oral contraceptive agent consisting of a progesterone receptor modulator, which does not affect endogenous estrogen levels, has been developed. Ulipristal acetate (UPA) has been used in a single high dose for emergency contraception and has been used continuously for up to six months for treatment of uterine fibroids. Low dose continuous usage of oral UPA is anticipated to inhibit ovulation and provide an estrogen free, bleed free method of contraception. The Eunice Kennedy Shriver National Institutes of Child Health and Human Development (NICHD) has a mission to develop safe and effective contraceptives for women, including obese women. Obesity is the number one public health issue facing the US population and is an independent risk for venous thromboembolism (VTE). Therefore, there is a public health need to develop effective contraception for woman that does not increase the risk of VTE. One Food and Drug Administration (FDA)-approved contraceptive method is the progestin-only pill (POP). This method requires strict adherence to taking the POP at the same time every day. The method is associated with irregular bleeding which often leads to discontinuation of the method. Daily low dose oral progesterone receptor modulators (PRMs), such as UPA, have been shown to inhibit ovulation and cause amenorrhea. The endogenous estrogen level is not affected by the PRM. Thus, the method will provide a regimen that is easier to follow than POP regimen and have a theoretically lower risk of VTE, especially for obese women. In addition, there is in vitro evidence that UPA may have protective activity against breast cancer. In order to provide preliminary evidence that daily, low dose UPA could be effective for contraception, a clinical trial will be conducted in the NICHD Contraceptive Clinical Trials Network (CCTN). The proposed study will be evaluated sequentially. Initially, women of reproductive age, with normal menstrual cycles, will receive treatment for 12 weeks (three 28-day cycles) in order to evaluate the mechanisms of contraceptive efficacy, safety and acceptability of this new contraceptive.

为了降低静脉血栓栓塞 (VTE) 的风险，特别是肥胖女性，需要无雌激素避孕药。一种由黄体酮受体调节剂组成的新型口服避孕药已经开发出来，它不会影响内源性雌激素水平。醋酸乌利司他（UPA）已以单次高剂量用于紧急避孕，并连续使用长达六个月来治疗子宫肌瘤。低剂量连续使用口服 UPA 预计会抑制排卵并提供无雌激素、无出血的避孕方法。 尤尼斯·肯尼迪·施赖弗国家儿童健康和人类发展研究所 (NICHD) 的使命是为女性（包括肥胖女性）开发安全有效的避孕药具。肥胖是美国人口面临的头号公共卫生问题，也是静脉血栓栓塞 (VTE) 的独立风险。因此，公共卫生需要为女性开发不会增加 VTE 风险的有效避孕方法。美国食品和药物管理局 (FDA) 批准的一种避孕方法是纯孕激素避孕药 (POP)。这种方法需要严格遵守每天同一时间服用POP。该方法与不规则出血有关，这通常导致该方法停止。每日低剂量口服孕酮受体调节剂 (PRM)，例如 UPA，已被证明会抑制排卵并导致闭经。内源性雌激素水平不受 PRM 影响。因此，该方法将提供比 POP 方案更容易遵循的方案，并且理论上 VTE 风险较低，尤其是对于肥胖女性。此外，有体外证据表明 UPA 可能具有预防乳腺癌的活性。为了提供初步证据证明每日低剂量UPA可以有效避孕，NICHD避孕临床试验网络（CCTN）将进行一项临床试验。拟议的研究将按顺序进行评估。最初，具有正常月经周期的育龄妇女将接受为期12周的治疗（三个28天的周期），以评估这种新型避孕药的避孕功效、安全性和可接受性的机制。