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

CCTN - 一项多中心、随机研究，旨在评估每日口服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: 9573644
• 负责人: KURT BARNHART
• 金额: $ 1.51万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 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 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9573644
• 关键词: Acetates; Adherence; Adverse effects; Aftercare; Age; Amenorrhea; Attitude; Biopsy; Blood specimen; Breast; Cervix Mucus; Chlamydia; Clinic; Clinical; Clinical Chemistry; Clinical Trials; Clinical Trials Network; Contraceptive Agents; Contraceptive History; Contraceptive methods; Counseling; Data; Dose; Drug Kinetics; Eligibility Determination; Endometrial; Endometrium; Estradiol; Estrogens; Future; Gonorrhea; Guidelines; Gynecology; Height; Hematology; Hemorrhage; In Vitro; Informed Consent; Interruption; Luteal Phase; Measurement; Measures; Medical; Menstrual cycle; Methods; Mission; National Institute of Child Health and Human Development; Non obese; Obesity; Oral; Ovulation; Pap smear; Pattern; Pharmaceutical Preparations; Pharmacodynamics; Phase; Physiologic pulse; Population; Positioning Attribute; Pregnancy; Pregnancy Tests; Procedures; Progesterone; Progesterone Receptors; Progestins; Protocols documentation; Public Health; Randomized; Recording of previous events; Recovery; Recruitment Activity; Regimen; Reproductive History; Rest; Risk; Rupture; SHBG gene; Safety; Sampling; Serum; Specific qualifier value; Thick; Thromboembolism; Time; Transvaginal Ultrasound; United States Food and Drug Administration; Urine; Venous; Visit; Weight; Woman; arm; base; birth control; contraceptive efficacy; data exchange; demographics; diaries; follow-up; malignant breast neoplasm; pill; reproductive; screening; treatment duration

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.

尤尼斯·肯尼迪·施赖弗国家儿童健康与人类发展研究所 (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 女性。肥胖是美国人口面临的头号公共卫生问题，也是一个 静脉血栓栓塞（VTE）的独立风险。因此，公共卫生需要 为女性制定不会增加 VTE 风险的有效避孕措施。一种食物和 药物管理局 (FDA) 批准的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。方法 与不规则出血有关，这通常会导致该方法的停止。日常的 低剂量口服孕酮受体调节剂 (PR.WLS)，例如 UPA，已被证明可以 抑制排卵，引起闭经。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 理论上，VTE 的风险较低，尤其是对于肥胖女性而言。此外，还有体外 有证据表明 UP A 可能具有预防乳腺癌的作用。为了提供 初步证据表明，每日低剂量 UP A 可有效避孕，这是一项临床研究 试验将在 NICHD 避孕临床试验网络 (CCTN) 中进行。这 拟议的研究将按顺序进行评估。最初，育龄妇女具有正常的 月经周期，将接受 12 周的治疗（三个 28 天的周期）以进行评估 这种新型避孕药的避孕功效、安全性和可接受性机制。 受试者将被随机分为 3 个组： • 第 1 组：UP A 每天口服 5 毫克，持续 24 天，然后停药间隔 4 次 天，重复3次。 • 第2 组：UP A 10 mg，每天口服，持续84 天（12 周），不间断。 • 第3 组：每天口服UPA 5 mg，持续84 天（12 周），不间断。