A Phase III, randomized, open label, non-inferiority study comparing the efficacy and safety of furazidin vaginal tablets and clindamycin vaginal cream in the local treatment of bacterial vaginosis

The primary objective is to demonstrate non-inferiority of furazidin 5 mg vaginal tablets compared to clindamycin 2% vaginal cream in the treatment efficacy of bacterial vaginosis. This comparison is clinically relevant as it evaluates whether furazidin, a nitrofuran derivative with bacteriostatic activity, provides therapeutic outcomes comparable to clindamycin, a lincosamide antibiotic, which is an established treatment option for bacterial vaginosis.

The secondary objectives include:

• To demonstrate non-inferiority of furazidin 5 mg vaginal tablets compared to clindamycin cream 2% in achieving microbiological cure.

• To demonstrate that the safety profile of furazidin 5 mg vaginal tablets, based on the incidence of adverse events, serious adverse events, and bacterial vaginosis recurrences, is not worse than clindamycin cream 2%.

• To demonstrate that participants' quality of life during and after treatment with furazidin 5 mg vaginal tablets is not worse than with clindamycin cream 2%.

The sponsor did not provide information regarding the total number of participants enrolled in this clinical trial. The study population consisted exclusively of **female participants** aged **18 to 65 years** diagnosed with **bacterial vaginosis** based on Amsel's criteria and confirmed by a positive BV blue test result. Participants were required to have a negative **pregnancy test** prior to enrollment and could not be lactating or planning pregnancy during the study period. Women of childbearing potential were required to use highly effective contraceptive methods or abstain from heterosexual intercourse throughout the study duration. Regarding lifestyle considerations, participants were required to refrain from using intravaginal products, including spermicides, condoms, and tampons, during the treatment period. Additionally, participants needed to have a negative test result for **low-grade squamous intraepithelial lesion (LSIL)**, **high-grade squamous intraepithelial lesion (HSIL)**, or malignancy within the past 12 months, or undergo **PAP smear** testing during screening according to the Bethesda classification. The trial population represented adult and elderly female patients with confirmed bacterial vaginosis who met specific reproductive health and diagnostic criteria.

This is a **Phase III**, **randomized**, **open-label**, **non-inferiority** clinical trial evaluating the efficacy and safety of **furazidin** vaginal tablets compared to **clindamycin** vaginal cream in the local treatment of **bacterial vaginosis**. The study employs a controlled design with two treatment arms: the test product consisting of furazidin 5 mg vaginal tablets and the comparator product consisting of clindamycin 2% vaginal cream. Both investigational medicinal products are administered via **vaginal use** for a treatment period of 7 days, with a maximum daily dose of 5 g for clindamycin cream and 5 mg for furazidin tablets. The primary objective is to demonstrate that treatment with furazidin vaginal tablets is not less effective than treatment with clindamycin vaginal cream. The estimated recruitment start date is December 2025, with an estimated study completion date of December 2027.

Eligible participants include female patients aged 18 to 65 years with bacterial vaginosis diagnosed based on **Amsel's criteria**. Key inclusion criteria require a written informed consent, a positive BV blue test result, negative **PAP smear** results for intraepithelial lesions or malignancy within the past 12 months, and negative pregnancy test for women of childbearing potential. Participants must agree to use highly effective contraception methods or abstain from heterosexual intercourse throughout the study period and must refrain from using intravaginal products during treatment, including spermicides, condoms, and tampons. Postmenopausal status is confirmed by absence of menses for 12 months or elevated **follicle stimulating hormone** levels in the postmenopausal range.

The study consists of multiple scheduled visits to assess treatment outcomes and safety. The screening visit (baseline) includes eligibility assessment, diagnostic testing using Amsel's criteria, **Nugent score** evaluation, PAP smear if required, pregnancy testing, and quality of life assessment using a **VAS scale**. Following randomization, participants receive the assigned treatment for 7 days. Visit 3, designated as the test of cure visit, occurs on Day 8-10 after treatment initiation and serves as the primary endpoint assessment. At this visit, **clinical cure** is evaluated based on resolution of abnormal vaginal discharge, negative **whiff test**, and presence of clue cells at less than 20% of total epithelial cells on microscopic examination of saline wet mount. Visit 4 takes place on Day 21-30 to assess Nugent score and determine the percentage of participants achieving scores ranging from 0 to 3. Long-term follow-up visits extend to at least 13 or 14 weeks after treatment completion to evaluate bacterial vaginosis recurrence rates within 12 weeks of follow-up and changes in quality of life from baseline.

The **primary endpoint** is the clinical cure rate at Visit 3 based on Amsel criteria. **Secondary endpoints** include the percentage of participants with Nugent scores ranging from 0 to 3 at Visit 4, the percentage achieving both clinical cure at Visit 3 and Nugent scores of 0 to 3 at Visit 4, incidence of **adverse events** and **serious adverse events** related and unrelated to the investigational medicinal product, percentage of bacterial vaginosis recurrences within 12 weeks among participants who achieved clinical cure, and assessment of quality of life changes from baseline to end of observation using VAS scale. The total participant involvement spans approximately 13 to 14 weeks from treatment initiation through the final follow-up visit. Conditions that may lead to early termination from the study include withdrawal of informed consent, pregnancy during the study period, development of serious adverse events requiring discontinuation, protocol violations, or investigator decision based on safety concerns.

The experimental treatment in this clinical trial consists of **furazidin** vaginal tablets containing 5 mg of the active substance. Furazidin is a **nitrofuran derivative** that acts as an **antimicrobial drug** with **bacteriostatic activity**. The pharmaceutical form is a **vaginal tablet** administered via **vaginal use**. The maximum daily dose is 5 mg, with a maximum total dose of 5 mg per administration. The treatment period extends for a maximum of 7 days. The product is manufactured by ADAMED SP. Z O.O. and the active substance is of chemical origin.

The comparator treatment utilized in this study is **clindamycin phosphate** vaginal cream, marketed as Dalacin 20 mg/g. Clindamycin is a **lincosamide antibiotic** and is also known as **clindamycin-2-dihydrogen phosphate**. The pharmaceutical form is a **vaginal cream** administered via **vaginal use**. The maximum daily dose is 5 grams, with a maximum total dose of 5 grams per administration. The treatment duration is 7 days, consistent with the experimental treatment regimen. The product is manufactured by PFIZER KFT. and holds marketing authorization number OGYI-T-958/10 in Hungary. The active substance is of chemical origin.

Efficacy will be assessed using clinical and microbiological parameters to evaluate treatment response in patients with **bacterial vaginosis**. The primary endpoint is the clinical cure rate at Visit 3 (test of cure, Day 8-10), based on Amsel criteria. Clinical cure is defined as the resolution of abnormal vaginal discharge, a negative whiff test, and the presence of clue cells at less than 20% of the total epithelial cells on microscopic examination of the saline wet mount.

Secondary efficacy endpoints include the percentage of participants with a Nugent score ranging from 0 to 3 at Visit 4 (Day 21-30), and the percentage of participants who achieved clinical cure at Visit 3 (Day 8-10) and had a Nugent score ranging from 0 to 3 at Visit 4 (Day 21-30). The percentage of bacterial vaginosis recurrences within 12 weeks of follow-up will be assessed using Amsel criteria in participants who achieved clinical cure status at Visit 3 (Day 8-10). Additionally, participants' quality of life will be assessed based on a VAS scale from the baseline visit to the end of the observation at Visit 5 (at least in week 13 or 14 after end of treatment). The positive result of the BV blue test is utilized as part of the diagnostic assessment.