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

尤尼斯·肯尼迪·施莱弗国家儿童健康和人类发展研究所 (NICHD)的使命是为包括肥胖在内的妇女开发安全有效的避孕药具 女人。肥胖是美国民众面临的头号公共健康问题，也是 静脉血栓栓塞(VTE)的独立风险。因此，有一种公共卫生需要 为妇女制定有效的避孕措施，而不会增加VTE的风险。One Food和 美国药品监督管理局(FDA)批准的避孕方法是仅限孕激素的避孕药(POP)。 这种方法需要严格遵守每天同一时间服用POP。方法 与不规则出血有关，这往往会导致该方法的中止。每天 小剂量口服孕激素受体调节剂(PR.WLS)，如uPA，已被证明可以 抑制排卵，导致闭经。内源性雌激素水平不受 PRM。因此，该方法将提供比POP方案更容易遵循的方案，并且 从理论上讲，患静脉血栓栓塞症的风险较低，特别是对于肥胖女性。此外，还有体外培养的 证据表明UP A可能对乳腺癌有保护作用。为了提供 初步证据表明，每日低剂量尿激素A可能对避孕有效，临床 试验将在NICHD避孕临床试验网络(CCTN)进行。这个 建议的研究将按顺序进行评估。最初，育龄妇女，与正常 月经周期，将接受为期12周(三个28天周期)的治疗，以评估 这种新型避孕药的避孕效果、安全性和可接受性的机制。 受试者将被随机分成3组： ·第1组：每日口服优降糖5毫克，连续24天，之后停药间隔4天 天数，重复3次。 2组：每日口服尿激素A 10 mg，连续服药84天(12周)。 3组：每日口服uPA 5 mg，连续服药84天(12周)。

The Eunice Kennedy Shriver National Institute 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 (PR.WlS) , 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 a POP regimen and have a theoretically lower risk of VTE, especially for obese women. In addition, there is in vitro evidence that UP A may have protective activity against breast cancer. In order to provide preliminary evidence that daily, low dose UP A 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. Subjects will be randomized into 3 arms: • Group 1: UP A 5 mg taken orally daily for 24 days followed by a pill-free interval of 4 days, repeated 3 times. • Group 2: UP A 10 mg taken orally daily for 84 days (12 weeks) without interruption. • Group 3: UPA 5 mg taken orally daily for 84 days (12 weeks) without interruption.