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

Phase 1

Not yet recruiting

• Conditions: Cervix; Intraepithelial Neoplasia, Grade II; Cervix Cancer; Cervix; Intraepithelial Neoplasia, Grade I; Cervix Intraepithelial Neoplasia Grade 3
• Interventions: Drug: Artesunate pessary; Diagnostic Test: blood draws for pharmacokinetics of the study drug

• Registration Number: NCT06263582
• Lead Sponsor: UNC Lineberger Comprehensive Cancer Center

Brief 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.

Study Timeline

• Study First Submitted: 2024-02-08
• Study First Submitted QC: 2024-02-08
• Study First Posted: 2024-02-16
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-09
• Last Update Posted: 2024-07-10
• Study Start: 2024-08
• Primary Completion: 2025-02
• Study Completion: 2025-02

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 16

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Artesunate vaginal inserts/ pessaries	Artesunate pessary	Artesunate vaginal inserts/pessaries are used as a treatment for cervical precancerous lesions.
Artesunate vaginal inserts/ pessaries	blood draws for pharmacokinetics of the study drug	Artesunate vaginal inserts/pessaries are used as a treatment for cervical precancerous lesions.

Primary Outcome Measures

Name	Time	Method
To determine the area under the plasma concentration versus time curve (AUC) of dihydroartemisinin	Day 5	To determine the area under the plasma concentration versus time curve (AUC) of dihydroartemisinin (DHA) following five consecutive days of self-administration of 200mg Artesunate vaginal inserts (pessaries. Mean DHA AUC will be submitted.

Secondary Outcome Measures

Name	Time	Method
To determine the maximum concentration of dihydroartemisinin (DHA) (Cmax)	Day 5	To determine the maximum concentration of dihydroartemisinin (DHA) (Cmax) following five consecutive days of self-administration of 200mg Artesunate vaginal inserts (pessaries) among healthy women.; Mean DHA Cmax (ng/ml) value will be submitted.
To determine the time to maximum concentration (Tmax) of Artesunate (AS) following five consecutive days	Day 5	To determine the time to maximum concentration (Tmax) of Artesunate (AS) following five consecutive days of self-administration of 200mg Artesunate vaginal inserts (pessaries) among healthy women.; Mean DHA Tmax (mins) value will be submitted.
To determine the area under the plasma concentration versus time curve (AUC) of Artesunate (AS)	Day 5	To determine the area under the plasma concentration versus time curve (AUC) of Artesunate (AS) following five consecutive days of self-administration of 200mg Artesunate vaginal inserts (pessaries).; Mean artesunate AUC will be submitted.
To determine the maximum concentration of Artesunate (AS)	Day 5	To determine the maximum concentration of Artesunate (AS) (Cmax) following five consecutive days of self-administration of 200mg Artesunate vaginal inserts (pessaries) among healthy women.; Mean artesunate Cmax (ng/ml) value will be submitted.
To determine the apparent clearance (CL/F) of Artesunate (AS)	Day 5	To determine the apparent clearance (CL/F) of Artesunate (AS) following five consecutive days of self-administration of 200mg Artesunate vaginal inserts (pessaries) among healthy women.; Mean Artesunate clearance (L/Kg/hr) will be submitted.
To determine the apparent clearance (CL/F) of dihydroartemisinin (DHA)	Day 5	To determine the apparent clearance (CL/F) of dihydroartemisinin (DHA) following five consecutive days of self-administration of 200mg Artesunate vaginal inserts (pessaries) among healthy women.; Mean DHA clearance (L/Kg/hr) will be submitted.
To determine the time to maximum concentration (Tmax) of dihydroartemisinin (DHA	Day 5	To determine the time to maximum concentration (Tmax) of dihydroartemisinin (DHA) following five consecutive days of self-administration of 200mg Artesunate vaginal inserts (pessaries) among healthy women.; Mean (Tmax) will be submitted.
To determine the half-life (t1/2) of Artesunate (AS)	Day 5	To determine the half-life (t1/2) of Artesunate (AS) following five consecutive days of self-administration of 200mg Artesunate vaginal inserts (pessaries) among healthy women.; Mean Artesunate half-life (t1/2) (mins) will be submitted.
To determine the half-life (t1/2) of dihydroartemisinin (DHA)	Day 5	To determine the half-life (t1/2) of dihydroartemisinin (DHA) following five consecutive days of self-administration of 200mg Artesunate vaginal inserts (pessaries) among healthy women.; Mean DHA half-life (mins) will be submitted.
To determine the volume of distribution (V/F) of Artesunate (AS)	Day 5	To determine the volume of distribution (V/F) of Artesunate (AS) following five consecutive days of self-administration of 200mg Artesunate vaginal inserts (pessaries) among healthy women.; Mean Artesunate volume of distribution (L/Kg) will be submitted.
To determine the volume of distribution (V/F) of dihydroartemisinin (DHA)	Day 5	To determine the volume of distribution (V/F) of dihydroartemisinin (DHA) following five consecutive days of self-administration of 200mg Artesunate vaginal inserts (pessaries) among healthy women.; Mean dihydroartemisinin (DHA) of distribution (V/F) will be submitted.
Type, frequency, severity, and duration of adverse events	Up to day 5	To investigate the safety of a 5-day course of self-administered intravaginal artesunate vaginal inserts (pessary) in women. Type, frequency, severity, and duration of reported and observed adverse events (AEs) using the U.S National Cancer Institute Common Terminology Criteria for Adverse Events, v5.0 (CTCAE 5.0) and the Division of AIDS Female Genital Adverse Events Grading Table will be submitted.

Trial Locations

Locations (1)

Lumumba Sub-County Hospital; 🇰🇪 Kisumu, Kenya