Clinical trial NCT06263582: Pharmacokinetics of Intravaginal, Self-administered Artesunate Vaginal Pessaries Among Women in Kenya
Official title: Pharmacokinetics of Intravaginal, Self-administered Artesunate Vaginal Pessaries Among Women in Kenya
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cervix Cancer
Cervix Intraepithelial Neoplasia Grade 3
Cervix; Intraepithelial Neoplasia, Grade I
Cervix; Intraepithelial Neoplasia, Grade II
Keywords: Artesunate
dihydroartemisinin
pharmacokinetics
Lead sponsor: UNC Lineberger Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2024-02-16
Enrollment: 12
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: To determine the area under the plasma concentration versus time curve (AUC) of dihydroartemisinin
timeFrame: Day 5
Secondary outcomes:
measure: To determine the area under the plasma concentration versus time curve (AUC) of Artesunate (AS)
timeFrame: Day 5
measure: To determine the maximum concentration of Artesunate (AS)
timeFrame: Day 5
measure: To determine the maximum concentration of dihydroartemisinin (DHA) (Cmax)
timeFrame: Day 5
measure: To determine the time to maximum concentration (Tmax) of Artesunate (AS) following five consecutive days
timeFrame: Day 5
measure: To determine the time to maximum concentration (Tmax) of dihydroartemisinin (DHA
timeFrame: Day 5
measure: To determine the half-life (t1/2) of Artesunate (AS)
timeFrame: Day 5
measure: To determine the half-life (t1/2) of dihydroartemisinin (DHA)
timeFrame: Day 5
measure: To determine the apparent clearance (CL/F) of Artesunate (AS)
timeFrame: Day 5
measure: To determine the apparent clearance (CL/F) of dihydroartemisinin (DHA)
timeFrame: Day 5
measure: To determine the volume of distribution (V/F) of Artesunate (AS)
timeFrame: Day 5
measure: To determine the volume of distribution (V/F) of dihydroartemisinin (DHA)
timeFrame: Day 5
measure: Type, frequency, severity, and duration of adverse events
timeFrame: Up to day 5
Other outcomes:
Locations:
city: Kisumu
country: Kenya
facility: Lumumba Sub-County Hospital
Study officials:
affiliation: UNC Lineberger Comprehensive Cancer Center
name: Chemtai Mungo, MD, MPH, FACOG
role: PRINCIPAL_INVESTIGATOR
References: