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Completed

NCT Number: NCT06263582

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.

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Key information

Conditions

Cervix Cancer Carcinoma Carcinoma in Situ Cervix Intraepithelial Neoplasia Grade 3 Cervix; Intraepithelial Neoplasia, Grade I Cervix; Intraepithelial Neoplasia, Grade II Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genital Diseases Genital Diseases, Female Genital Neoplasms, Female Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Lymphatic Diseases Lymphoma Lymphoma, Follicular Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Precancerous Conditions Urogenital Diseases Urogenital Neoplasms Uterine Cervical Diseases Uterine Cervical Dysplasia Uterine Cervical Neoplasms Uterine Diseases Uterine Neoplasms

Age range

18 year–65 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 1

Primary location

Lumumba Sub-County Hospital

Kisumu, Kenya

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age 18 years or older
  • Negative pregnancy test at screening
  • Willingness to use contraception (hormonal or barrier) during the 5-day study dosing phase if of childbearing age (less than 50 years of age)
  • Ability and willingness to provide informed consent.

Exclusion criteria

  • Current pregnancy or breastfeeding status
  • History of total hysterectomy
  • Known allergy to Artesunate.
  • Have a medical comorbidity that in the opinion of the investigator would interfere with study participation.
  • Currently receiving artemisinin-based agents for malaria treatment or completed artemisinin-based treatment within the previous 3 days.

Treatment and study plan

Artesunate pessary

Drug

Subjects will use the study pessaries, placed in the vagina every day for 5 consecutive days.

blood draws for pharmacokinetics of the study drug

Diagnostic Test

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.

Primary outcomes

  1. To Determine the Area Under the Plasma Concentration Versus Time Curve (AUC) of Dihydroartemisinin

    Time frame: 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 outcomes

  1. To Determine the Area Under the Plasma Concentration Versus Time Curve (AUC) of Artesunate (AS)

    Time frame: 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.

  2. To Determine the Maximum Concentration of Artesunate (AS)

    Time frame: 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.

  3. To Determine the Maximum Concentration of Dihydroartemisinin (DHA) (Cmax)

    Time frame: 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.

  4. To Determine the Time to Maximum Concentration (Tmax) of Artesunate (AS) Following Five Consecutive Days

    Time frame: 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 (hours) value will be submitted.

  5. To Determine the Time to Maximum Concentration (Tmax) of Dihydroartemisinin (DHA

    Time frame: 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.

  6. To Determine the Half-life (t1/2) of Artesunate (AS)

    Time frame: 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.

  7. To Determine the Half-life (t1/2) of Dihydroartemisinin (DHA)

    Time frame: 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.

  8. To Determine the Apparent Clearance (CL/F) of Artesunate (AS)

    Time frame: 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.

  9. To Determine the Apparent Clearance (CL/F) of Dihydroartemisinin (DHA)

    Time frame: 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.

  10. To Determine the Volume of Distribution (V/F) of Artesunate (AS)

    Time frame: 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.

  11. To Determine the Volume of Distribution (V/F) of Dihydroartemisinin (DHA)

    Time frame: 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.

  12. Type, Frequency, Severity, and Duration of Adverse Events

    Time frame: Up to day 10 days

    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.

Sponsors and collaborators

Lead sponsor

UNC Lineberger Comprehensive Cancer Center

Other

Collaborators

  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Registry information

Important dates

Study start
2024
Primary completion
2024
Study completion
2024
First posted
Feb 16, 2024
Registry last updated
Aug 19, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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