Contraception
Conditions
Keywords
Long Acting Reversible Contraceptive
Brief summary
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.
Detailed description
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.
Interventions
DRUG22.2 mg Etonogestrel (ENG)
Subdermal insertion of a single Casea S pellet (22.2 mg ENG) in healthy female participants
DRUG44.4 mg Etonogestrel (ENG)
Subdermal insertion of two Casea S pellets (44.4 mg ENG) in healthy female participants
Sponsors
FHI 360
Bill and Melinda Gates Foundation
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
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, vital signs, and physical exam * has regular menstrual cycle (21 to 35 days) * not at risk for pregnancy (i.e., sterilized) * has a Body Mass Index (BMI) of 18 to 29.9 * 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 investigational site for the follow-up procedures and assessments as specified in this protocol * Part 2 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 on immunosuppressive therapy * has migraine with aura * has undiagnosed abnormal vaginal bleeding * has known or suspected breast cancer, history of breast cancer or other progestin-sensitive cancer * has current or history of cervical cancer * has cirrhosis, liver tumors (benign or malignant), or active liver disease * has one or more baseline liver function test(s) above the local laboratory's normal range * has a hemoglobin \<10.5 g/dL * 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 (listed in Section 6.3.3.4.4.1 of the study protocol) * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum observed serum concentration (Cmax) | 12 weeks; 52 weeks; 114 weeks | Maximum observed serum concentration (Cmax) measured by blood samples collected at multiple timepoints before and after pellet insertion |
| Time to Cmax (tmax) | 12 weeks; 52 weeks; 114 weeks | Time to Cmax (tmax) measured by blood samples collected at multiple timepoints before and after pellet insertion |
| Geometric mean serum ENG concentration | 28 days; 84 days; 114 weeks | Geometric mean serum ENG concentration at treatment days 28 and 84 |
| Area under concentration time curve (AUC 0-28) | 28 days; 84 days; 154 days; 364 days | Area under the concentration time curve through days 28 and day 84 |
| Predicted concentration at day 546 and probability of exceeding 90 pg/mL through day 546 | 52 weeks | pharmacokinetics of ENG after subdermal insertion of 2 Casea S pellets |
| Assessment of the removability of Casea S pellets | up to 26 weeks | Number and descriptions of incidence of removal complications |
| Assessment Casea S pellets removability | up to 26 weeks | Time of the procedure duration of procedure |
| Ability to completely remove the pellet and ease of removal | up to 26 weeks | Physician's assessment of the removability of Casea S pellets qualified as "complete removal, partial removal, or not removed" on the study removal assessment. |
| Time to undetectable ENG levels | 114 weeks | Apparent absorption half-life; Predicted concentration at day 546 and probability of exceeding 90 pg/mL through day 546; Time above 90 pg/mL |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of treatment emergent adverse events, significant changes in vital signs, weight, vaginal bleeding patterns and perceptions, abnormalities in serum chemistry, occurrence of implant site reactions | up to 114 weeks | Safety and tolerability of Casea S pellets measured by the occurrence of treatment emergent adverse events, significant changes in vital signs, weight, vaginal bleeding patterns and perceptions, abnormalities in serum chemistry, occurrence of implant site reactions |
| Assessment of the ease of insertion of Casea S pellets | up to 114 weeks | Physician's report of success and ease of insertion. Ease of insertion qualified as "easy, moderate, or difficult" on the study insertion assessment. |
| Assessment of the duration of Casea S pellets insertion | up to 114 weeks | Time of the procedure duration |
| Assessment of the complications of insertion of Casea S pellets | up to 114 weeks | Number and descriptions of the incidence of insertion complications. |
| Follicular and luteal activity following subdermal insertion of Casea S pellets | up to 114 weeks | Estradiol (E2) and progesterone (P4) levels |
| Estimate of ENG release rates using explant analysis | up to 114 weeks | Cumulative amount of ENG released over time, average daily release in 3 months and up to 130 weeks |
Countries
Dominican Republic
Contacts
PRINCIPAL_INVESTIGATORKavita Nanda, M.D.
FHI 360
Outcome results
None listed