CENTRAL LABORATORY FOR PHARMACOKINETIC/PHARMACODYNAMIC EVALUATION OF LEVONORGESTREL BUTANOATE FOR FEMALE CONTRACEPTION

I.BACKGROUND 有一种对无雌激素避孕的需求，以减少静脉血栓栓塞（VTE）的风险，特别是对肥胖妇女。研制了一种新的丁酸左炔诺孕酮（LB）长效注射制剂。左炔诺孕酮（LNG）在各种避孕药（避孕药、宫内节育器和植入物）中的临床应用历史悠久，其有效性和安全性得到了广泛认可。 尤尼斯·肯尼迪·施莱佛国家儿童健康和人类发展研究所（NICHD）的使命是为妇女，包括肥胖妇女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，是静脉血栓栓塞症（VTE）的独立风险。因此，公共卫生需要为肥胖女性开发有效的避孕方法，而不会增加VTE的风险。美国食品和药物管理局（FDA）批准的一种避孕方法是仅孕激素药丸（POP）或所谓的“迷你药丸”，主要由哺乳期妇女使用，仅持续几个月，并要求严格遵守每天在同一时间服用POP。不含雌激素的长效注射型LB将提供一种比POP更容易遵循的方案，并且理论上具有较低的VTE风险，特别是对于肥胖女性。为了提供LB可能有效避孕的初步证据，将在NICHD避孕临床试验网络（CCTN）中进行临床试验。拟定的研究将在育龄女性中进行，以评价这种新型避孕药的药代动力学、避孕有效性机制和安全性。入组受试者将接受LB单次注射。将评价通过肌内和皮下注射途径给药。招募将包括入组约50%的BMI >=32 kg/m2但小于40 kg/m2的受试者。 II.SCOPE 根据方案规定，测量激素和其他生物学试验，作为中心实验室，评价长效注射剂丁酸左炔诺孕酮（LB）的药代动力学和药效学效应、周期控制和安全性。 III.OBJECTIVES 获得有效和可靠的测定数据，以确定长效注射剂丁酸左炔诺孕酮（LB）的药代动力学和药效学效应、周期控制和安全性，并将当前研究的数据与先前对原始制剂进行的LB研究相关联

I.BACKGROUND There is a demand for estrogen-free contraception to reduce the risk of venous thromboembolism (VTE), particularly for obese women. A new long-acting formulation of levonorgestrel butanoate (LB) delivered by injection has been developed. Levonorgestrel (LNG) has a long history of clinical use in a variety of contraceptives (pills, intrauterine devices, and implants) and its efficacy and safety are well recognized. 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 obese woman that does not increase the risk of VTE. One Food and Drug Administration (FDA) -approved contraceptive method is the progestin-only pill (POP) or so-called “mini pill,” which is used mainly by lactating women only for several months and requires strict adherence to taking the POP at the same time every day. A long-acting injectable form of LB that is estrogen-free will provide a regimen that is easier to follow than a POP and have a theoretically lower risk of VTE especially for obese women. In order to provide preliminary evidence that LB could be effective for contraception, a clinical trial will be conducted in the NICHD Contraceptive Clinical Trials Network (CCTN). The proposed study will be conducted in women of reproductive age in order to evaluate pharmacokinetics, the mechanisms of contraceptive efficacy, and safety of this new contraceptive. The enrolled subjects will receive a single injection of LB. Drug administration via intramuscular and subcutaneous routes of injection will be evaluated. The Recruitment will include enrollment of approximately 50% of subjects with BMI >=32 kg/m2 but less than 40 kg/m2. II.SCOPE To measure hormones and other biological assays as defined by the protocol, serving as the central laboratory to evaluate the pharmacokinetics and the pharmacodynamic effects, cycle control, and safety of levonorgestrel butanoate (LB) formulated as a long-acting injectable. III.OBJECTIVES To obtain valid and reliable assay data to determine the pharmacokinetics and the pharmacodynamic effects, cycle control, and safety of levonorgestrel butanoate (LB) formulated as a long-acting injectable and to relate the data from the current study to the previous study of LB conducted on the original formulation