Casea S Contraceptive Implants (Casea S) Trial

Contraception Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05174884
• Other study ID #: 1630531
• Status: Recruiting
• Phase: Phase 1
• Start date: December 13, 2023
• Est. completion date: March 2025

Study information

• Verified date: February 2024
• Source: FHI 360
• Contact: Kavita Nanda, M.D.
• Phone: 919-321-3592
• Email: knanda[@]fhi360.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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, 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: March 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 45 Years

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

Related Conditions & MeSH terms

• Contraception

Intervention

Drug:
• 22.2 mg Etonogestrel (ENG)
Subdermal insertion of a single Casea S pellet (22.2 mg ENG) in healthy female participants
• 44.4 mg Etonogestrel (ENG)
Subdermal insertion of a two Casea S pellet (44.4 mg ENG) in healthy female participants
• 22.2-66.6 mg Etonogestrel (ENG)
Subdermal insertion of 1-3 Casea S pellets (22.2 - 66.6 mg ENG) in healthy female participants

Locations

Country	Name	City	State
Dominican Republic	Clinica Profamilia	Santo Domingo	DN

Sponsors (2)

Lead Sponsor	Collaborator
FHI 360	Bill and Melinda Gates Foundation

Country where clinical trial is conducted

Dominican Republic, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum observed serum concentration (Cmax)	Maximum observed serum concentration (Cmax) measured by blood samples collected at multiple timepoints before and after pellet insertion	12 weeks; 52 weeks; 130 weeks
Primary	Time to Cmax (tmax)	Time to Cmax (tmax) measured by blood samples collected at multiple timepoints before and after pellet insertion	12 weeks; 52 weeks; 130 weeks
Primary	Geometric mean serum ENG concentration	Geometric mean serum ENG concentration at treatment days 28 and 84	28 days; 130 weeks
Primary	Area under concentration time curve (AUC 0-28)	Area under the concentration time curve through days 28 and day 84	28 days; 154 days; 364 days
Primary	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	52 weeks
Primary	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	130 weeks
Secondary	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	up to 130 weeks
Secondary	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.	up to 130 weeks
Secondary	Assessment of the duration of Casea S pellets insertion	Time of the procedure duration	up to 130 weeks
Secondary	Assessment of the complications of insertion of Casea S pellets	Number and descriptions of the incidence of insertion complications.	up to 130 weeks
Secondary	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.	up to 130 weeks
Secondary	Assessment Casea S pellets removability	Time of the procedure duration of procedure	up to 130 weeks
Secondary	Assessment of the removability of Casea S pellets	Number and descriptions of incidence of removal complications	up to 130 weeks
Secondary	Follicular and luteal activity following subdermal insertion of Casea S pellets	Estradiol (E2) and progesterone (P4) levels	up to 130 weeks
Secondary	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	up to 130 weeks