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

Cervix Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06263582
• Other study ID #: IGHID12333
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: June 2024
• Est. completion date: February 2025

Study information

• Verified date: February 2024
• Source: UNC Lineberger Comprehensive Cancer Center
• Contact: Chemtai P Mungo, MD, MPH, MSc
• Phone: 919-966-5280
• Email: chemtai_mungo[@]med.unc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 16
• Est. completion date: February 2025
• Est. primary completion date: February 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria

1. Age 18 years or older

2. Negative pregnancy test at screening

3. Willingness to use contraception (hormonal or barrier) during the 5-day study dosing phase if of childbearing age (less than 50 years of age)

4. Ability and willingness to provide informed consent.

Exclusion Criteria

1. Current pregnancy or breastfeeding status

2. History of total hysterectomy

3. Known allergy to Artesunate.

4. Have a medical comorbidity that in the opinion of the investigator would interfere with study participation.

5. Currently receiving artemisinin-based agents for malaria treatment or completed artemisinin-based treatment within the previous 3 days.

Related Conditions & MeSH terms

• Carcinoma in Situ
• Cervix Cancer
• Neoplasms
• Uterine Cervical Neoplasms

Intervention

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.

Locations

Country	Name	City	State
Kenya	Lumumba Sub-County Hospital	Kisumu

Sponsors (1)

Lead Sponsor	Collaborator
UNC Lineberger Comprehensive Cancer Center

Country where clinical trial is conducted

Kenya, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the area under the plasma concentration versus time curve (AUC) of dihydroartemisinin	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.	Day 5
Secondary	To determine the area under the plasma concentration versus time curve (AUC) of Artesunate (AS)	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.	Day 5
Secondary	To determine the maximum concentration of Artesunate (AS)	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.	Day 5
Secondary	To determine the maximum concentration of dihydroartemisinin (DHA) (Cmax)	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.	Day 5
Secondary	To determine the time to maximum concentration (Tmax) of Artesunate (AS) following five consecutive days	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.	Day 5
Secondary	To determine the time to maximum concentration (Tmax) of dihydroartemisinin (DHA	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.	Day 5
Secondary	To determine the half-life (t1/2) of Artesunate (AS)	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.	Day 5
Secondary	To determine the half-life (t1/2) of dihydroartemisinin (DHA)	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.	Day 5
Secondary	To determine the apparent clearance (CL/F) of Artesunate (AS)	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.	Day 5
Secondary	To determine the apparent clearance (CL/F) of dihydroartemisinin (DHA)	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.	Day 5
Secondary	To determine the volume of distribution (V/F) of Artesunate (AS)	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.	Day 5
Secondary	To determine the volume of distribution (V/F) of dihydroartemisinin (DHA)	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.	Day 5
Secondary	Type, frequency, severity, and duration of adverse events	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.	Up to day 5

External Links

•   University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials