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

I.BACKGROUND 人们需要无雌激素的避孕药，以降低静脉血栓栓塞症(VTE)的风险，特别是对肥胖女性。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孕激素的药丸(POP)或所谓的“迷你药丸”，主要供哺乳期妇女使用几个月，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。NICHD避孕临床试验网络(CCTN)将进行一项临床试验，以提供LB在避孕方面有效的初步证据。这项拟议的研究将在育龄妇女中进行，以评估这种新避孕药的药代动力学、避孕效果的机制和安全性。登记的受试者将接受一次LB注射。将评估通过肌肉内和皮下注射途径给药。此次招募将包括大约50%体重指数为32公斤/平方米但小于40公斤/平方米的受试者。 II.SCOPE 测量方案定义的激素和其他生物测定，作为中央实验室，评估作为长效注射剂的左炔诺孕酮丁酸酯(LB)的药代动力学和药效学效果、周期控制和安全性。 III.OBJECTIVES 获得有效和可靠的分析数据，以确定作为长效注射剂的左旋诺孕酮丁酸酯(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在原始配方上进行的LB研究联系起来

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