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| ID | Type | Description | Link |
|---|---|---|---|
| K12HD103085 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Artesunate vaginal inserts/ pessaries | Experimental | Artesunate vaginal inserts/pessaries are used as a treatment for cervical precancerous lesions. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Artesunate pessary | Drug | Subjects will use the study pessaries, placed in the vagina every day for 5 consecutive days. |
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| 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 |
| 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 |
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Inclusion Criteria
Exclusion Criteria
Women are eligible
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| Name | Affiliation | Role |
|---|---|---|
| Chemtai Mungo, MD, MPH, FACOG | UNC Lineberger Comprehensive Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Lumumba Sub-County Hospital | Kisumu | Kenya |
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| Label | URL |
|---|---|
| University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials | View source |
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Twelve participants consented and found eligible.
Participants were recruited in one center in Kenya.
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| ID | Title | Description |
|---|---|---|
| FG000 | Artesunate Vaginal Inserts/ Pessaries | Artesunate vaginal inserts/pessaries are used as a treatment for cervical precancerous lesions. Artesunate pessary: Subjects will use the study pessaries, placed in the vagina every day for 5 consecutive days. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 14, 2023 |
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| 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. |
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| 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 |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Artesunate Vaginal Inserts/ Pessaries | Artesunate vaginal inserts/pessaries are used as a treatment for cervical precancerous lesions. Artesunate pessary: Subjects will use the study pessaries, placed in the vagina every day for 5 consecutive days. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Level of education | Count of Participants | Participants |
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| Occupation | Count of Participants | Participants |
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| Marital Status | Count of Participants | Participants |
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| Electricity available | Count of Participants | Participants |
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| Tap water available | Count of Participants | Participants |
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| Current or prior tobacco use | Count of Participants | Participants |
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| Current or prior alcohol use | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Mean | Standard Deviation | ng/mL-h | Day 5 |
|
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| ||||||||||||||||||||||||||
| 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. | Posted | Mean | Standard Deviation | ng/mL-h | Day 5 |
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| 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. | Posted | Mean | Standard Deviation | ng/mL | Day 5 |
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| 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. | Posted | Mean | Standard Deviation | ng/mL | Day 5 |
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| 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 (hours) value will be submitted. | Posted | Mean | Standard Deviation | hours | Day 5 |
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| 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. | Posted | Mean | Standard Deviation | hours | Day 5 |
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| 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. | The plasma half-life of Artesunate could not be estimated because the concentration versus time profiles did not reach an elimination phase (i.e., the concentration versus time profile did not decrease) from 0 to 8h post administration of intravaginal artesunate. | Posted | Day 5 |
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| 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. | The plasma half-life of dihydroartemisinin (DHA) could not be estimated because the concentration versus time profiles did not reach an elimination phase (i.e., the concentration versus time profile did not decrease) from 0 to 8h post administration. | Posted | Day 5 |
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| 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. | The plasma apparent clearance (CL/F) of Artesunate could not be estimated because the concentration versus time profiles of both forms did not reach an elimination phase (i.e., the concentration versus time profile did not decrease) from 0 to 8h post administration of intravaginal artesunate. | Posted | Day 5 |
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| 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. | The plasma apparent clearance (CL/F) of dihydroartemisinin (DHA) could not be estimated because the concentration versus time profiles of both forms did not reach an elimination phase (i.e., the concentration versus time profile did not decrease) from 0 to 8h post administration. | Posted | Day 5 |
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| 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. | The plasma volume of distribution (V/F) of Artesunate (AS) could not be estimated because the concentration versus time profiles of both forms did not reach an elimination phase (i.e., the concentration versus time profile did not decrease) from 0 to 8h post administration of intravaginal artesunate. | Posted | Day 5 |
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| 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. | The plasma volume of distribution (V/F) of dihydroartemisinin (DHA) could not be estimated because the concentration versus time profiles of both forms did not reach an elimination phase (i.e., the concentration versus time profile did not decrease) from 0 to 8h post administration. | Posted | Day 5 |
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| 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. | Posted | Count of Participants | Participants | Up to day 10 days |
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Up to ten days after the study intervention (vaginal insertion of Artesunate pessaries).
AEs were collected according to National Cancer Institute Common Terminology Criteria for Adverse Events, v5.0 (CTCAE 5.0)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Artesunate Vaginal Inserts/ Pessaries | Artesunate vaginal inserts/pessaries are used as a treatment for cervical precancerous lesions. Artesunate pessary: Subjects will use the study pessaries, placed in the vagina every day for 5 consecutive days. | 0 | 12 | 0 | 12 | 8 | 12 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal Pain | Gastrointestinal disorders | CTCAE 5.0 | Non-systematic Assessment |
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| Vaginal discharge | Reproductive system and breast disorders | CTCAE 5.0 | Non-systematic Assessment |
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| Toothache | Gastrointestinal disorders | CTCAE 5.0 | Non-systematic Assessment |
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| Vaginal fistula | Reproductive system and breast disorders | CTCAE 5.0 | Non-systematic Assessment |
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| Pain in the extremity | Musculoskeletal and connective tissue disorders | CTCAE 5.0 | Non-systematic Assessment |
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| Vaginal pruritis | Reproductive system and breast disorders | CTCAE 5.0 | Non-systematic Assessment |
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Pharmacokinetic (PK) sampling from 0 to 8 hours after intravaginal administration of artesunate was not sufficient to capture the elimination phase of the drug and its metabolite. As a result, key plasma pharmacokinetic parameters including apparent clearance (CL/F), apparent volume of distribution (Vd/F), elimination half-life (t½), and area under the concentration-time curve from time zero to infinity (AUC₀-∞) could not be estimated.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Sorgi Kate | UNC Lineberger Comprehensive Cancer Center | 919-966-5280 | kasorgi@email.unc.edu |
| Jul 22, 2025 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D002583 | Uterine Cervical Neoplasms |
| D002578 | Uterine Cervical Dysplasia |
| D002278 | Carcinoma in Situ |
| D008224 | Lymphoma, Follicular |
| ID | Term |
|---|---|
| D014594 | Uterine Neoplasms |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D002577 | Uterine Cervical Diseases |
| D014591 | Uterine Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
| D011230 | Precancerous Conditions |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| student |
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