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

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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.