Casea S Contraceptive Implants (Casea S) Trial

Study Overview
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Brief Summary
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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.

Detailed Description
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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, eight 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. Based on PK modeling from Parts 1 and 2, investigators will select one or more doses of Casea S for Part 3. In Part 3 of this study, approximately 18 women will each have Casea S pellets (range 1-3 pellets) 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.

Official Title
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A Phase 1 Clinical Trial to Evaluate the Pharmacokinetics, Removability, Safety, and Tolerability of Casea S Contraceptive Implants

Conditions
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Contraception

Intervention / Treatment
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* Drug: 22.2 mg Etonogestrel (ENG)
* Drug: 44.4 mg Etonogestrel (ENG)
* Drug: 22.2-66.6 mg Etonogestrel (ENG)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Casea S pellet<br>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. | Drug: 22.2 mg Etonogestrel (ENG)<br>* Subdermal insertion of a single Casea S pellet (22.2 mg ENG) in healthy female participants<br>* Other names: Casea S;|
| Experimental: Two Casea S pellets<br>In Part 2 of this study, eight women will each have two Casea S pellets (44.4 mg ENG) inserted into the inner aspect of the non-dominant upper arm. | Drug: 44.4 mg Etonogestrel (ENG)<br>* Subdermal insertion of a two Casea S pellet (44.4 mg ENG) in healthy female participants<br>* Other names: Casea S;|
| Experimental: Variable Casea S pellets<br>Based on PK modeling from Parts 1 and 2, the investigator will select one or more doses of Casea S for Part 3. In Part 3 of this study, approximately 18 women will each have Casea S pellets (range 1-3 pellets) inserted into the inner aspect of the non-dominant upper arm. | Drug: 22.2-66.6 mg Etonogestrel (ENG)<br>* Subdermal insertion of 1-3 Casea S pellets (22.2 - 66.6 mg ENG) in healthy female participants<br>* Other names: Casea S;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ENG concentrations in serum |  | 130 weeks | 
| Removability of Casea S pellet (s) using a Likert scale |  | 12 weeks | 
| Removability of Casea S pellet (s) using a Likert scale |  | 26 weeks | 
| Removability of Casea S pellet (s) using a Likert scale |  | 52 weeks | 
| Removability of Casea S pellet (s) using a Likert scale |  | 78 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events |  | up to 130 weeks | 
| Incidence of clinically observed insertion site reactions |  | up to 130 weeks | 
| Incidence of insertion site reactions using participant diaries |  | up to 130 weeks | 
| Incidences of Abnormal liver function tests |  | up to 130 weeks | 
| Changes in vaginal bleeding patterns from baseline using participant diaries |  | up to 130 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Long Acting Reversible Contraceptive