NCT06263582

Pharmacokinetics of Intravaginal, Self-administered Artesunate Vaginal Pessaries Among Women in Kenya

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: UNC Lineberger Comprehensive Cancer Center · Academic / Other
• Sex: Female
• Age: 18 Years – 65 Years
• Healthy volunteers: Accepted

Summary

This study investigates the pharmacokinetics of Artesunate (AS) and dihydroartemisinin (DHA), the active metabolite of Artesunate, following intravaginal use at the dosing and frequency being studied for cervical precancer treatment. A secondary objective is to investigate safety among study participants.

Detailed description

Due to lack of access to primary and secondary prevention, women living in low-and middle-income countries bear a disproportionate burden of cervical cancer, accounting for 90% of new cases and 85% of deaths globally. Cervical cancer can be prevented through vaccination against Human papillomavirus (HPV), whose infection is required to develop cervical cancer. Among unvaccinated women, screening for HPV or cervical precancer allows identification of precancerous lesions - primarily cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3), that can be treated and cured, to prevent progression to cancer. Most CIN2/3 lesions that are left untreated will progress to invasive cervical cancer. Current treatments for CIN2/3 in both high- and low-resource countries (LMICs) require trained health care providers, who are often out of reach for many women, particularly in rural areas in LMICs. Lack of access to precancer treatment following screening in LMICs in part accounts for the high burden of incident cervical cancer. Preclinical data have demonstrated pro-apoptotic effects of Artesunate (AS), a commonly available drug with an excellent safety profile in oral, rectal and intravenous routes primarily used to treat malaria in LMICs. This led to a recent Phase I study in the United States that demonstrated that self-administered vaginal artesunate inserts (pessaries) are safe, well-tolerated, and demonstrate efficacy for treatment of CIN2/3. Based on the mechanism of action, the clinical safety profile, and widespread availability as a generic drug on the World Health Organization (WHO) List of Essential Medications, vaginal artesunate inserts (pessaries), if backed by data from randomized trials, may offer patient-controlled and access cervical precancer treatment method for women in LMICs who face the greatest burden of cervical cancer and have difficulty accessing skilled providers for precancer treatment. However, given that artesunate is a well-known drug used in malaria treatment, it is critical to ensure that vaginal application of the drug will not promote resistance for use in malaria treatment.

Conditions

• Cervix Cancer
• Cervix Intraepithelial Neoplasia Grade 3
• Cervix; Intraepithelial Neoplasia, Grade I
• Cervix; Intraepithelial Neoplasia, Grade II

Interventions

Type	Name	Description
DRUG	Artesunate pessary	Subjects will use the study pessaries, placed in the vagina every day for 5 consecutive days.
DIAGNOSTIC_TEST	blood draws for pharmacokinetics of the study drug	On day 5, all participants will have their blood draws before they use the pessary, and at 15 min, 30 mins, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours after inserting the pessary. Blood samples will be tested for the pharmacokinetics of the study drug.

Timeline

• Start date: 2024-05-29
• Primary completion: 2024-08-14
• Completion: 2024-08-14
• First posted: 2024-02-16
• Last updated: 2025-08-19
• Results posted: 2025-08-19

Locations

1 site across 1 country: Kenya