Overview

This is a single-center, three-part, Phase 1 study to evaluate the pharmacokinetics (PK) of ENG, removability, safety, and tolerability of Casea S pellets inserted subdermally in healthy women of reproductive age. The goal is to select for further investigation a dose of Casea S that is both safe and has a PK profile consistent with contraceptive protection for at least 78 weeks.

Eligibility

Inclusion Criteria:

Participants may be included in the study if they meet all of the following criteria:

• willing and able to provide signed informed consent
• female between 18 to 45 years of age (inclusive)
• healthy based on results of medical evaluation including medical history and vital signs tests
• has regular menstrual cycle (21 to 35 days)
• not at risk for pregnancy and not intending future pregnancy (i.e., sterilized)-Part 1 only
• has a low risk of pregnancy (i.e., sterilized, in exclusively same-sex partnership, abstinent, in monogamous relationship with vasectomized partner, using non-hormonal intrauterine device (IUD)-Parts 2 and 3
• has a Body Mass Index (BMI) of 18 to 29, inclusive
• provides normal mammogram results within the last year before enrollment for women 40 or older
• is willing and able to comply with all study requirements and return to the site for the follow-up procedures and assessments as specified in this protocol
• Part 3 participants only: has daily access to a smartphone, tablet , or computer with internet access.

Exclusion Criteria:

        Participants will be excluded from participating in this study if they meet any of the
        following criteria:
          -  has multiple risk factors for cardiovascular disease (e.g., smoking, diabetes,
             obesity, hypertension, high LDL (low density lipoprotein), or high triglyceride
             levels)
          -  has current or history of ischemic heart disease or cerebrovascular disease
          -  has current or previous thromboembolic disorders
          -  has systemic lupus erythematosus
          -  has rheumatoid arthritis and on immunosuppressive therapy
          -  has migraine with aura
          -  has unexplained vaginal bleeding
          -  has current or history of breast cancer, or undiagnosed mass detected by breast exam
          -  has current or history of cervical cancer
          -  has cirrhosis, liver tumors, or active liver disease
          -  has a hemoglobin <10.5 g/dL
          -  has one or more baseline liver function test(s) above the local laboratory's normal
             range
          -  has used any injectable contraceptive in the past 6 months
          -  has used any of the following medications within 4 weeks before enrollment:
               -  any investigational drug
               -  prohibited drugs (Section 5.5.1)
               -  oral contraceptives, contraceptive ring, or patch
               -  levonorgestrel intrauterine device (LNG IUD) or contraceptive implant
          -  is pregnant
          -  is currently breastfeeding
          -  desires to become pregnant in the subsequent 30 months
          -  has been pregnant in last 3 months
          -  is using or planning to use prohibited drugs for their intended study duration
          -  has abnormal cervical cytology requiring treatment
          -  has known sensitivity to ENG
          -  plans to move to another location in the next 30 months
          -  is participating in any other clinical trial with a biomedical intervention
          -  has any condition (social or medical), that in the opinion of the site investigator
             would make study participation unsafe, would interfere with adherence to the clinical
             study requirements or complicate data interpretation