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

一、背景 人们需要无雌激素避孕药来降低静脉血栓栓塞 (VTE) 的风险，特别是对于肥胖女性。一种新的注射用左炔诺孕酮丁酸酯（LB）长效制剂已被开发出来。左炔诺孕酮 (LNG) 在各种避孕药具（丸剂、宫内节育器和埋植剂）中有着悠久的临床应用历史，其功效和安全性得到了广泛认可。 尤尼斯·肯尼迪·施赖弗国家儿童健康和人类发展研究所 (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。肥胖是美国人口面临的头号公共卫生问题，也是静脉血栓栓塞 (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，且不会增加 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纯孕激素避孕药 (POP) 或所谓的“迷你避孕药”，主要供哺乳期妇女使用，只能使用几个月，并且需要严格遵守每天在同一时间服用 POP。不含雌激素的长效注射 LB 将提供比 POP 更容易遵循的治疗方案，并且理论上 VTE 的风险较低，尤其是对于肥胖女性。为了提供LB可有效避孕的初步证据，将在NICHD避孕临床试验网络（CCTN）进行临床试验。拟议的研究将在育龄妇女中进行，以评估这种新型避孕药的药代动力学、避孕功效机制和安全性。登记的受试者将接受单次 LB 注射。将评估通过肌内和皮下注射途径的药物给药。招募将包括大约 50% BMI >= 32 kg/m2 但小于 40 kg/m2 的受试者的招募。 二、范围 测量方案定义的激素和其他生物测定，作为中心实验室评估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。 三、目标 获得有效且可靠的测定数据，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