| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| E.1.1.1 | Medical condition in easily understood language |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10004055 |
| E.1.2 | Term | Bacterial vaginosis |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
To evaluate the safety and efficacy of Furazidin vaginal tablets in patients with Bacterial Vaginosis.
To perform a proof of concept study to establish the most appropriate dosage (dosage regimen and treatment duration) to take forth into a phase III trial. Four different doses of study drugs as well as the comparator (Clindamycin cream 2%) will be applied vaginally to adult women with clinical signs and symptoms of vaginal infections caused by Bacteria spp.
In addition, the safety and local tolerability of four tested doses of the study drug will be assessed.
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| E.2.2 | Secondary objectives of the trial |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. A written informed consent signed before any study-specific evaluation is performed.
2. Female patients with age ≥ 18 and ≤ 50 years.
3. Patients requiring treatment for bacterial vaginosis.
4. PAP smear/tests in accordance with the Bethesda classification will be performed for subjects who do not have a negative test for intraepithelial lesion or malignancy or atypical squamous cells of undetermined significance in the past 24 months; in circumstances where the results of the PAP smear are pending at the time of randomization, eligible subjects may be randomized..
5. Women of childbearing potential must have a negative pregnancy test before randomization and may not be lactating or planning to become pregnant during the study period (up to Follow Up Visit 4 – Day 21-30).
6. Agreement of female subject of childbearing potential to use highly effective methods of contraception (progestin intrauterine device, all oral contraceptives, transdermal hormonal contraceptives) or to abstain from sexual intercourse during the treatment.
7. Willing to refrain from the use of intravaginal products during the treatment period (including spermicides, condoms, tampons etc.).
8. The positive result of BV blue test. |
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| E.4 | Principal exclusion criteria |
1. Patients with clinical symptoms of other infectious causes of vulvovaginitis (e.g., vulvovaginal candidiasis, Trichomonas vaginalis, Chlamydia trachomatis, Neisseria gonorrhoeae, Herpes simplex, or human papillomavirus).
2. Patients with another vaginal or vulvar condition, which would confound the interpretation of the clinical response.
3. Patients who are currently receiving antibacterial therapy unrelated to BV
4. Known hypersensitivity/allergy to active ingredients of the study medications.
5. Vaginismus, dyspareunia.
6. Urinary tract infection within the 2 weeks prior to the study start or during it. Uncomplicated UTI patients usually presence of at least two of the following clinical symptoms: dysuria, urinary frequency, urinary urgency, suprapubic pain.
7. Clinically significant liver or kidney function impairment (eGFR<60 ml/min/1.73m2).
8. History of recurrent bacterial vaginosis (≥3 episodes per year).
9. Clinically significant cardiovascular function impairment.
10. Severe hypertension and non-controlled diabetes.
11. Presence of known risk or of venous or arterial thromboembolism.
12. Undiagnosed abnormal vaginal bleeding, bleeding disorders, genital tumors which in opinion of investigator are clinically significant.
13. Pregnancy and/or breastfeeding.
14. Participation in any other trial 30 days before initiation of the study.
15. Postmenopausal women.
16. Abuse of alcohol.
17. Any gynecological condition contraindicating the use of vaginal ovule or cream.
18. Use of any other local or systemic bactericidal, anti-protozoa or antifungal agent within the 2 weeks prior to the study start or during it.
19. Use spermicides, or diaphragms, intravaginal contraception delivery system, probiotics, hygiene products containing probiotics.
20. Presence of a sexually transmitted disease such as syphilis, gonorrhea, human papilloma virus, herpes zoster virus etc.(excluding Ureaplasma, Mycoplasma).
21. Previously diagnosed human immunodeficiency virus seropositivity or clinically diagnosed acquired immunodeficiency syndrome or its related complex.
22. Immunosuppressive condition (eg, end-stage renal disease) or is currently taking immunosuppressants, (eg, steroids, cyclosporine).
23. Malignancy of any type.
24. Any other condition the Investigator believes would interfere with the subject’s ability to provide informed consent, comply with study instructions, or puts the subject at undue risk.
25. The positive result of SARS-CoV-2 test.
26. Presence of test for intraepithelial lesion or malignancy or atypical squamous cells of undetermined significance (in case of ASCUS the test should be repeated) .
27. Women currently menstruating or expecting menstruation within 1 week.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
1. Safety and local tolerability – incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) related and unrelated to IMP.
Safety and local tolerability assessment based on Likert scale of the signs/symptoms:
• Assessed by physician:
Verbal evaluation of local symptoms and naked eye inspection of visible epithelial surface will be performed. Patients will be questioned and clinician will verify the following symptomps according to the Likert like scale (NO, MILD, MODERATE, MODERATE TO SEVERE, SEVERE):
o Discharge (normal/abnormal)
o Dysuria
o Irritation
o Puffiness
o Hyperemia of the mucosa
• Reported by patient
Self-reporting evaluations will be performed by patients according to the Likert like scale (NO, MILD, MODERATE, MODERATE TO SEVERE, SEVERE):
o Burning
o Discharge (normal/abnormal)
o Dysuria
o Discomfort
o Irritation
o Itching
o Pain
2. Clinical endpoint – the Day 8/9 assessment of clinical cure rate based on the Amsel criteria (vaginal pH > 4.5, presence of clue cells, KOH test as well as greyish white, malodorous discharge), where clinical cure is defined as: the resolution of the 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. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
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| E.5.2 | Secondary end point(s) |
1. Day 5 /6 assessment of clinical cure rate based on the Amsel criteria (vaginal pH > 4.5, presence of clue cells, KOH test as well as greyish white, malodorous discharge), where clinical cure is defined as: the resolution of the 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.
2. Percentage of subjects with Nugent score ranging from 0 to 3 (Visit 4, Day 21-30)
3. Percentage of responders with outcome defined as a clinical cure plus Nugent score ranging from 0 to 3 (Visit 4, Day 21-30)
4. Assessment of patient quality of life with 5 treatments modalities (from the baseline visit to the end of the treatment)
5. Assessment of the patients’ compliance
6. The percentage of Bacterial Vaginosis recurrences within 12 weeks of follow-up
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 5 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 15 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| LONG-TERM FOLLOW UP visit/END OF STUDY |
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 11 |
| E.8.9.1 | In the Member State concerned days | 29 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 11 |
| E.8.9.2 | In all countries concerned by the trial days | 29 |
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