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

女性避孕用左炔诺孕酮丁酸酯药代动力学/药效学评价中心实验室

• 批准号: 10369906
• 负责人: ALISON EDELMAN
• 金额: $ 12.06万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-09 至 2023-02-08
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10369906
• 关键词: Adherence; Age; Biological Assay; Body mass index; Clinical; Clinical Trials; Clinical Trials Network; Contraceptive Agents; Contraceptive methods; Data; Drug Kinetics; Enrollment; Estrogens; Evaluation; Female Contraceptive Agents; Formulation; Free Will; Hormones; Implant; Injectable; Injections; Intramuscular; Intrauterine Devices; Laboratories; Lactation; Levonorgestrel; Measures; Mission; National Institute of Child Health and Human Development; Obesity; Pharmaceutical Preparations; Pharmacodynamics; Population; Progestins; Protocols documentation; Public Health; Recording of previous events; Regimen; Risk; Route; Safety; Time; United States Food and Drug Administration; Woman; contraceptive efficacy; pill; recruit; reproductive; subcutaneous; venous thromboembolism

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

I.Background 有无雌激素避孕的需求，以降低静脉血栓主义（VTE）的风险，特别是对于肥胖女性。已经开发了一种新的左旋杆菌丁酸盐（LB）的长效公式。左甲虫（LNG）在各种避孕药（药丸，内脏设备和incrans）中具有悠久的临床用途史，其有效性和安全性得到充分认可。 Eunice Kennedy Shriver国家儿童健康与人类发展研究所（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。肥胖是美国人口面临的第一大公共卫生问题，是静脉血栓疗法（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，而肥胖女性不会增加VTE的风险。一种食品药物管理局（FDA）批准的避孕方法是纯孕激素药物（POP）或所谓的“迷你药”，主要是通过哺乳女性使用几个月来使用，并且需要严格的依从性，以每天同时在同一时间进行流行。不含雌激素的长效注射型LB形式将提供一种比POP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。为了提供LB可以有效避孕的初步证据，将在NICHD避孕试验网络（CCTN）中进行临床试验。拟议的研究将在生殖年龄的女性中进行，以评估药代动力学，避孕效果的机制以及这种新避孕药的安全性。注册的受试者将获得LB的单一注射。将评估通过肌内和皮下注射途径进行药物给药。招募将包括大约50％的BMI> = 32 kg/m2但小于40 kg/m2的受试者入学。 II.Scope 测量该方案定义的激素和其他生物学，是评估药代动力学的中央实验室以及左旋甲状腺肿丁烷（LB）（LB）的药物动力学效应，循环控制和安全性，该实验室（LB）以长效的注射式注射。 iii。目标 获得有效可靠的测定数据，以确定药代动力学以及左右甲状腺素（LB）的药物动力学，周期控制和安全性（LB），以长效注射为长效注射，并将当前研究中的数据与先前在原始公式进行的LB研究相关联