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

评价IM或SQ注射丁酸左炔诺孕酮(LB)用于女性避孕的PK和PD的研究

• 批准号: 10859762
• 负责人: CLINT DART
• 金额: $ 34.67万
• 依托单位: HEALTH DECISIONS INC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-25 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10859762
• 关键词: Adherence; Age; Body mass index; Clinical; Clinical Trials; Clinical Trials Network; Contraceptive Agents; Contraceptive methods; Dose; Drug Kinetics; Enrollment; Estrogens; Female Contraceptive Agents; Formulation; Free Will; Hepatotoxicity; Implant; Injectable; Injections; Intramuscular; Intrauterine Devices; Lactation; Levonorgestrel; Mission; Monitor; National Institute of Child Health and Human Development; Obesity; Population; Progestins; Public Health; Recording of previous events; Regimen; Risk; Risk Reduction; Route; Safety; Services; Time; United States Food and Drug Administration; Woman; contraceptive efficacy; follow-up; pill; recruit; reproductive; service coordination; subcutaneous; venous thromboembolism

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.

为了降低静脉血栓栓塞（VTE）的风险，需要无雌激素避孕，特别是对于肥胖女性。研制了一种新的丁酸左炔诺孕酮（LB）长效注射剂。左炔诺孕酮（LNG）在各种避孕药（药丸、宫内节育器和植入物）中具有长期的临床使用历史，并且其有效性和安全性是公认的。尤妮斯·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。一种食品和药物管理局（FDA）批准的避孕方法是 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可有效用于避孕的初步证据，通过NICHD避孕临床试验网络（CCTN）启动临床试验，其中将LB施用于育龄妇女以评价其药代动力学、作用机制和抗生育作用。 避孕效果和安全性。入组受试者已通过肌内和皮下注射途径接受LB。招募包括约50%的BMI >=30 kg/m2但小于40 kg/m2的受试者。迄今为止，与A组有关的所有活动， B和B2已完成。出于对可能的肝毒性和安全性的担忧，FDA对皮下LB进行了部分临床试验，并建议使用50 mg和60 mg进行单次剂量递增研究。C组（50 mg）的招募已结束，该组的入组人数接近 完成.该任务将提供统计和临床协调、随访和监测目前入组Caswell组的受试者，作为招募、入组、协调、随访、监测和完成与D组受试者相关的所有活动的支持服务。