A Phase I Study to Evaluate the PK and PD of a Single Injection of Levonorgestrel Butanoate for Female Contraception

To evaluate the levonorgestrel (LNG) pharmacokinetic (PK) profile following injection of a single 20 mg dose of levonorgestrel butanoate (LB).

This is a Phase I single center, open-label, single dose pharmacokinetic and pharmacodynamic study of an injectable formulation of levonorgestrel butanoate (LB) jointly developed by the National Institute of Child Health and Human Development (NICHD) and CONRAD, and manufactured by Coldstream Laboratories, Inc. Healthy normal weight and obese women will be followed as outpatients for up to eight months. During this study, subjects will undergo a screening cycle to confirm normal ovulatory function, and then receive active treatment with a single injection of LB. They will undergo frequent evaluations to obtain serum samples to evaluate drug levels and ovulatory function, as well as transvaginal ultrasound and cervical mucus evaluation at selected visits. Follow up will continue until normal ovulatory cycles resume. Based upon detailed studies in non-human primates, it is expected that most subjects will resume menstrual cyclicity within 12- 26 weeks following the injection. Subjects will continue to be followed for one normal cycle after return of menses. This study will be conducted by the NICHD at one of the Contraceptive Clinical Trials Network (CCTN) sites (Oregon Health \& Science University, (OHSU)) in the USA and will enroll approximately 16 women. This study will enroll approximately 16 subjects that demonstrate favorable cervical mucus and normal ovulatory function during a baseline cycle. Enrollment will be stratified to ensure that 50% of the subjects have a BMI \>32 kg/m2 and \<40 kg/m2 and approximately 50% of subjects have a BMI \<32 kg/m2.