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

I.BACKGROUND

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