NICHD:R&D:CENTRAL LABORATORY FOR A PHASE 2B STUDY TO EVALUATE THE EFFICACY AND SAFETY OF SUBCUTANEOUS LEVONORGESTREL BUTANOATE FOR FEMALE CONTRACEPTION:NON-SEVERABLE

Oregon Health & Science University, Portland OR

Investigators

Abstract

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 a major public health issue facing the United States (U.S.) population and is an independent risk for venous thromboembolism (VTE); therefore, there is a public health need to develop effective contraception for obese women that does not increase the risk of VTE. Progestin-only methods are not associated with an increased risk of VTE; methods approved for contraception in the U.S. include intrauterine, subcutaneous implant, injectable, and oral formulations. Injectable contraception represents a long-acting and reversible method that has the additional benefit of privacy as the user retains no evidence of use following the injection. An injectable contraceptive containing LB has been developed by (NICHD with the goal of reducing side effects and increasing the duration of action compared to the existing injectable progestin available in the U.S., depomedroxyprogesterone acetate (DMPA). Levonorgestrel (LNG) has a long history of clinical use in a variety of contraceptives (pills, intrauterine devices [IUDs], implants), and its efficacy and safety are well recognized (see investigator brochure [IB]). There continues to be demand for highly effective estrogen-free contraception because of the real, albeit small, risk of VTE with currently available estrogen-containing products. The NICHD restarted LB development in the last decade with a goal for self-administration. The current formulation promotes increased stability through a longer-lasting and more concentrated dosage than previous LB formulations. In addition, injectables have lower failure rates than contraceptive pills, patches, or rings without requiring daily, weekly, or monthly adherence. To evaluate the safety and efficacy of this promising product, CDP is conducting a multicenter, open-label, Phase 2b trial (CCN021b) through its Contraceptive Clinical Trials Network (CCTN). The study will enroll approximately 180 healthy women between 18 and 35 years of age across six U.S. clinical sites. Participants will receive two injections of LB spaced four months apart, with follow-up lasting for 8 months of contraception followed by a recovery period to document the return of ovulation and menstruation. This study is designed to generate key data on contraceptive efficacy, safety, tolerability, and acceptability, supporting the development of LB as a potential new injectable contraceptive option with an excellent safety profile, a low incidence of side effects, and more predictable return to fertility relative to currently available methods. The objective for this acquisition is to continue CPD’s development of LB to address FDA regulatory requirements and transition to approval for a Phase 3 study. This study will be separated into 4 separate phases, with distinct aims and deliverables and the central lab will conduct the assays needed for follow-up of subjects participating in the clinical trial. To measure hormones and other biological assays as defined by the protocol, serving as the central laboratory to support evaluation of contraceptive efficacy, pharmacokinetics, bleeding patterns, safety, and side effects of levonorgestrel butanoate. To obtain valid and reliable assay data to support continued evaluation of contraceptive efficacy, pharmacokinetics, bleeding patterns, safety, and side effects of LB, ensuring consistency with previously collected data in the Phase II development program.