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

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.

Study Overview

• Status: Completed
• Conditions: Cervix Cancer; Cervix Intraepithelial Neoplasia Grade 3; Cervix; Intraepithelial Neoplasia, Grade I; Cervix; Intraepithelial Neoplasia, Grade II
• Intervention / Treatment: Drug: Artesunate pessary; Diagnostic test: blood draws for pharmacokinetics of the study drug

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 Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Kenya
  • Kisumu, Kenya
    • Lumumba sub-County Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Artesunate vaginal inserts/ pessaries; Artesunate vaginal inserts/pessaries are used as a treatment for cervical precancerous lesions.

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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 (hours) value will be submitted.	Day 5
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
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
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
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
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
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
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
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 10 days

Collaborators and Investigators

• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Principal Investigator: Chemtai Mungo, MD, MPH, FACOG, UNC Lineberger Comprehensive Cancer Center

Publications and helpful links

Helpful Links

• University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2024
• Primary Completion (Actual): August 14, 2024
• Study Completion (Actual): August 14, 2024

Study Registration Dates

• First Submitted: February 8, 2024
• First Submitted That Met QC Criteria: February 8, 2024
• First Posted (Actual): February 16, 2024

Study Record Updates

• Last Update Posted (Actual): August 19, 2025
• Last Update Submitted That Met QC Criteria: July 31, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: pharmacokinetics; Artesunate; dihydroartemisinin
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Uterine Diseases; Genital Diseases, Female; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Carcinoma; Uterine Cervical Diseases; Uterine Neoplasms; Neoplasms; Carcinoma in Situ; Uterine Cervical Neoplasms; Anti-Infective Agents; Antineoplastic Agents; Antiviral Agents; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Anthelmintics; Schistosomicides; Antiplatyhelmintic Agents; Artesunate
• Other Study ID Numbers: IGHID12333; K12HD103085 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No