A STUDY TO EVALUATE THE PK AND PD OF IM OR SQ INJECTIONS OF LEVONORGESTREL BUTANOATE (LB) FOR FEMALE CONTRACEPTION

为了减少静脉血栓栓塞症(VTE)的风险，特别是对肥胖女性来说，需要无雌激素的避孕措施。本文报道了丁酸左旋诺孕酮长效注射制剂的研制。左炔诺孕酮(LNG)在各种避孕药(避孕药、宫内节育器和植入物)中的临床使用已有很长的历史，其有效性和安全性得到了广泛的认可。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妇女在内的妇女开发安全有效的避孕药具。肥胖是美国民众面临的头号公共健康问题，也是静脉血栓栓塞症(VTE)的独立风险。因此，有公共卫生需要为肥胖妇女制定有效的避孕措施，而不增加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 仅限黄体酮的药丸(POP)或所谓的“迷你药丸”，主要供哺乳期妇女使用，仅持续几个月，并要求严格遵守每天同一时间服用POP。 一种不含雌激素的长效注射形式的LB将提供一种比POP更容易遵循的养生法，理论上VTE的风险更低，尤其是对肥胖女性。为了提供初步证据证明LB可用于避孕，通过NICHD避孕临床试验网络(CCTN)启动了一项临床试验，在该网络中，LB用于育龄妇女，以评价其药代动力学、作用机制。 避孕药的有效性、安全性。登记的受试者通过肌肉内和皮下注射途径接受了LB。招募包括大约50%体重指数为30公斤/平方米但小于40公斤/平方米的受试者。到目前为止，所有与A组有关的活动， B，和B2已经完成。出于对可能的肝脏毒性和安全性的担忧，FDA已经部分临床搁置了皮下LB，并建议使用50 mg和60 mg进行单次递增剂量研究。C组(50 Mg)的招募工作已经结束，该组的招募工作已接近完成 完成。这项任务将提供统计和临床协调，跟踪和监测目前在卡斯韦尔小组登记的受试者，并为招募、登记、协调、后续行动、监测和完成与D组受试者有关的所有活动提供支助服务。

There is a demand for estrogen-free contraception in order 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 was initiated through the NICHD Contraceptive Clinical Trials Network {CCTN), in which LB was administered to women of reproductive age in order to evaluate its pharmacokinetics, mechanisms of contraceptive efficacy, and safety. The enrolled subjects have received LB via intramuscular and subcutaneous routes of injection. Recruitment has included enrollment of approximately 50% of subjects with BMI >=30 kg/m2 but less than 40 kg/m2. Thus far, all activities related to Groups A, B, and B2 have been completed. Out of concern for possible hepatotoxicity and safety, the FDA had placed a partial clinical hold on subcutaneous LB and suggested a single ascending dose study using 50mg and 60mg. Recruitment for Group C {50mg) has concluded and enrollment for this group is nearly complete. This task will provide for the statistical and clinical coordination, for the follow-up, and monitoring of subjects currently enrolled in Group Caswell as supporting services for the recruitment, enrollment, coordination, follow-up, monitoring, and completion of all activities related to subjects in Group D.