This is a single-center, two-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.
In Part 1 of this study, four women will each have a single Casea S pellet (22.2 mg ENG) inserted into the inner aspect of the non-dominant upper arm after a negative urine pregnancy test. The insertion site and pellet location will be verified, marked, and photographed. ISRs and AEs will be assessed. In Part 2 of this study, approximately sixteen women will each have two Casea S pellets (44.4 mg ENG) inserted into the inner aspect of the non-dominant upper arm. The insertion site and pellet location will be verified, marked, and photographed. ISRs and AEs will be assessed.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
20
Subdermal insertion of a single Casea S pellet (22.2 mg ENG) in healthy female participants
Subdermal insertion of a two Casea S pellet (44.4 mg ENG) in healthy female participants
Clinica Profamilia
Santo Domingo, DN, Dominican Republic
Maximum observed serum concentration (Cmax)
Maximum observed serum concentration (Cmax) measured by blood samples collected at multiple timepoints before and after pellet insertion
Time frame: 12 weeks; 52 weeks; 114 weeks
Time to Cmax (tmax)
Time to Cmax (tmax) measured by blood samples collected at multiple timepoints before and after pellet insertion
Time frame: 12 weeks; 52 weeks; 114 weeks
Geometric mean serum ENG concentration
Geometric mean serum ENG concentration at treatment days 28 and 84
Time frame: 28 days; 114 weeks
Area under concentration time curve (AUC 0-28)
Area under the concentration time curve through days 28 and day 84
Time frame: 28 days; 154 days; 364 days
Predicted concentration at day 546 and probability of exceeding 90 pg/mL through day 546
pharmacokinetics of ENG after subdermal insertion of 2 Casea S pellets
Time frame: 52 weeks
Assessment of the removability of Casea S pellets
Number and descriptions of incidence of removal complications
Time frame: up to 52 weeks
Assessment Casea S pellets removability
Time of the procedure duration of procedure
Time frame: up to 52 weeks
Ability to completely remove the pellet and ease of removal
Physician's assessment of the removability of Casea S pellets qualified as "complete removal, partial removal, or not removed" on the study removal assessment.
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Time frame: up to 52 weeks
Time to undetectable ENG levels
Apparent absorption half-life; Predicted concentration at day 546 and probability of exceeding 90 pg/mL through day 546; Time above 90 pg/mL
Time frame: 114 weeks
Occurrence of treatment emergency adverse events, significant changes in vital signs, weight, vaginal bleeding patterns and perceptions, abnormalities in serum chemistry, occurrence of implant site reactions
Safety and tolerability of Casea S pellets measured by the occurrence of treatment emergency adverse events, significant changes in vital signs, weight, vaginal bleeding patterns and perceptions, abnormalities in serum chemistry, occurrence of implant site reactions
Time frame: up to 114 weeks
Assessment of the ease of insertion of Casea S pellets
Physician's report of success and ease of insertion. Ease of insertion qualified as "easy, moderate, or difficult" on the study insertion assessment.
Time frame: up to 114 weeks
Assessment of the duration of Casea S pellets insertion
Time of the procedure duration
Time frame: up to 114 weeks
Assessment of the complications of insertion of Casea S pellets
Number and descriptions of the incidence of insertion complications.
Time frame: up to 114 weeks
Follicular and luteal activity following subdermal insertion of Casea S pellets
Estradiol (E2) and progesterone (P4) levels
Time frame: up to 114 weeks
Estimate of ENG release rates using explant analysis
Cumulative amount of ENG released over time, average daily release in 3 months and up to 130 weeks
Time frame: up to 114 weeks