Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma in Situ

Uterine Cervical Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Cervical Intraepithelial Neoplasia

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Artesunate

Antimalarials

Antiprotozoal Agents

Antiparasitic Agents

Antiviral Agents

Anthelmintics

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

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

Artesunate pessary

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.

blood draws for pharmacokinetics of the study drug

Chemtai P Mungo, MD, MPH, MSc

Katherine Sorgi

Chemtai Mungo, MD, MPH, FACOG

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

UNC Lineberger Comprehensive Cancer Center

Symptoms and General Pathology

Gland and Hormone Related Diseases

Syndrome

Polycystic Ovary Syndrome

Cysts

Ovarian Cysts

Ovarian Diseases

Adnexal Diseases

Gonadal Disorders

Endocrine System Diseases

Artenimol

The subjects take Dihydroartemisinin, 40mg tid for 12 weeks

Dihydroartemisinin 40mg three times a day for 12 consecutive weeks.

Dihydroartemisinin

Xiaoying Li, MD

Artemisinin has been widely used as a first-line antimalarial drug in routine clinical practice. In recent years, it has been reported that Artemisinin also has some significant anti-inflammatory, anti-tumor and immune-modulating effects. The investigators' previous studies discovered that Artemisinin dramatically reduced serum androgen levels and improved poly-cystic ovary syndrome(PCOS) in animals. Preliminary study by the investigators found that artemisinin derivatives are capable of reducing both androgen levels and improving insulin resistance, two clinical characteristics of PCOS. Thus artemisinin derivatives has the potential effect to alleviate PCOS symptoms. The current study aims to investigate the effect of artemisinin on improving PCOS and serum androgen levels in PCOS subjects.

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine metabolic disorder caused by a combination of genetic and environmental factors. The pathogenesis of PCOS remains unclear. Artemisinin has been widely used as a first-line antimalarial drug in routine clinical practice. In recent years, it has been reported that Artemisinin has significant anti-inflammatory, anti-tumor and immune-modulating effects. The investigator's previous studies found that artemisinin and its derivatives could significantly promote uncoupling protein 1 (UCP1) transcription and the conversion of white fat to brown fat. Artemisinin derivatives upregulated the levels of genes critical for brown fat differentiation and function, accompanied by enhanced mitochondrial biosynthesis, demonstrating their potential to promote white fat browning and improve metabolism in rodent models. The investigators also observed that androgen levels in drug-induced PCOS rats were reduced, when treated with artemether analogs for prophylactic and therapeutic purposes, respectively. It is believed that the two core mechanisms in the pathogenesis of PCOS are excessive androgen synthesis and insulin resistance. Preliminary study by the investigators found that artemisinin derivatives are capable of reducing both serum androgen levels and improving insulin resistance, two clinical characteristics of PCOS. Thus artemisinin derivatives has the potential effect to alleviate PCOS symptoms and control or even reverse the disease progression. The current study aims to investigate the effect of artemisinin on improving PCOS and serum androgen levels in PCOS subjects.

20 participants with PCOS receive dihydroartemisinin for 3 months

The Effect of Dihydroartemisinin in PCOS

The Evaluation of the Effect of Dihydroartemisinin in Patients With Polycystic Ovary Syndrome

Periodical vaginal bleeding by questionnaire

Length, width and height of bilateral ovaries measured by B type ultrasound

Total number of follicles with diameters \<10 mm measured by B type ultrasound

Shanghai Zhongshan Hospital

Director

The subjects take dihydroartemisinin, 40mg tid for 90 days

dihydroartemisinin 40mg tid po for 90 consecutive days

JINGJING JIANG, MD, PhD

The primary research hypothesis of this study is that dihydroartemisinin is effective in restoration of regular menstrual cycles of PCOS subjects who meet at least two of three Rotterdam Criteria. Secondary research hypotheses include: dihydroartemisinin is also effective in reducing androgen, total immature follicles, and anti-Mullerian hormone.

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine metabolic disorder caused by genetic and environmental factors. Artemisinin has been widely used as a first-line antimalarial drug in routine clinical practice. In recent years, artemisinin has also been reported to have significant anti-inflammatory, anti-tumor and immune-modulating effects. Our recent study revealed that artemisinin derivatives protect against PCOS development by inhibiting ovarian androgen production. Consistently in a small pilot study, dihydroartemisinin effectively reduced androgen levels, reduced immature follicles, and improved the estrous cycle in PCOS patients who strictly met all the three Rotterdam Criteria, namely hyperandrogenism, ovulation dysfunction, and polycystic ovaries on ultrasound. Nevertheless, clinical diagnosis of PCOS can be established as long as a patient fulfill two of the three Rotterdam Criteria. The present study aims to explore the therapeutic effects of dihydroartemisinin in patients with PCOS who met at least two of three (≥2) Rotterdam Criteria.

Efficacy of Dihydroartemisinin for Treating PCOS

Therapeutic Efficacy of Dihydroartemisinin in Patients With Polycystic Ovary Syndrome

Record of vaginal bleeding within 6 months after start taking dihydroartemisinin

Serum AMH before and after 90 days of medication

FAI (Total testosterone in nmol/L / SHBG in nmol/L X 100) before and after 90 days of medication

Total number of immature follicles measuring 2-9 mm in diameter on ultrasound before and after 90 days of medication

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pharmacokinetics of Intravaginal, Self-administered Artesunate Vaginal Pessaries Among Women in Kenya	NCT06263582	Cervix Cancer Cervix Intraepi... Cervix; Intraep... Cervix; Intraep...	Artesunate pess... blood draws for...	18 Years - 65 Years	UNC Lineberger Comprehensive Cancer Center
The Effect of Dihydroartemisinin in PCOS	NCT05465135	Polycystic Ovar...	Dihydroartemisi...	16 Years - 35 Years	Shanghai Zhongshan Hospital
Efficacy of Dihydroartemisinin for Treating PCOS	NCT06417099	Polycystic Ovar...	Dihydroartemisi...	18 Years - 40 Years	Shanghai Zhongshan Hospital
The Effect of Dihydroartemisinin in PCOS	NCT05465135	Polycystic Ovar...	Dihydroartemisi...	16 Years - 35 Years	Shanghai Zhongshan Hospital

Spots Global Cancer Trial Database for dihydroartemisinin