E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Uncomplicated vulvovaginal candidosis (VVC) |
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E.1.1.1 | Medical condition in easily understood language |
Diseases and disorders affecting the female sex organs; infectious disease of female breeding organs |
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E.1.1.2 | Therapeutic area | Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10047783 |
E.1.2 | Term | Vulvovaginal candida |
E.1.2 | System Organ Class | 100000054373 |
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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 assess the microbiological and clinical efficacy, the safety and acceptability of the benzydamine HCl 6 mg and econazole nitrate 150 mg vaginal pessary, in comparison to Pevaryl® 150 mg vaginal pessary, in the treatment of uncomplicated VVC. |
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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. Females between 18 and 65 years of age (limits included), with no limitation of race. 2. Patients clinically diagnosed with uncomplicated VVC, as confirmed by a positive vaginal wet mount test. 3. Patients presenting at baseline a total score ≥ 3 in the subjective symptoms and a total score ≥ 1 in the objective signs. 4. Female of childbearing potential and women in a postmenopausal state. Females of childbearing potential and women with no menses for a period < 12 months must have a negative pregnancy test at Visit 0 and have to agree not to start a pregnancy from the signature of the informed consent up to Visit 4, using an appropriate birth control method such as combined estrogen-progestin containing hormonal contraceptives (e.g. oral, transdermal), progestin-only hormonal contraceptives (e.g. oral, injectable, implantable), intrauterine device (IUD) or intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomised partner, sexual abstinence. The following definitions will be considered: • Woman of childbearing potential (WOCBP): i.e., fertile, following menarche and until becoming post-menopausal, unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. • A postmenopausal state is defined as no menses for 12 months without an alternative medical cause 5. Patients legally capable of giving their consent to participate in the study and available to sign and date the written informed consent. |
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E.4 | Principal exclusion criteria |
1. Known hypersensitivity or allergy to the active ingredients and/or to any component of the study medications. 2. Lactating and pregnant women. 3. Patients suffering from vaginitis of different etiology, bacterial vaginosis, Trichomonas vaginalis, Chlamydia trachomatis, Neisseria gonorrhoeae, Herpes simplex, or human papilloma virus, according to the medical history, physical and gynecological examination 4. Treatment with systemic antifungal drugs within 4 weeks or with topical antifungal drugs within 1 week before Visit 0. 5. Use of any topical drugs on the application area and systemic drugs, including over the counter, oral anticoagulants (i.e. warfarin or acenocoumarol), anti-inflammatory and/or analgesic drugs, antibiotics or antibacterials, within 2 weeks before Visit 0. Intravaginal hormonal contraceptives and male condom are not allowed. . 6. Patients with actual menstruation at Visit 0 or expected menstruation within 11 days after Visit 0. 7. Clinically significant abnormalities at physical examination, vital signs, ECG, laboratory tests at Visit 0. 8. Patients suffering from gynecological diseases (genital tract abnormalities, lichen sclerosus, post-operative alterations of the genital tract, genital tract neoplasm) that may interfere with the study end-points and/or procedures. 9. Immunocompromised patients or patients affected by non-controlled diabetes, or patients being treated with drugs (e.g. immunosuppressants, corticosteroids, anti-infectives), which may predispose to mycological infections. 10. Signs or symptoms or clinical documentation for concurrent infections (including but not limited to sexually transmitted infections) and/or neoplasm. 11. Patients suffering from chronic/recurrent vulvovaginal mycosis, defined as four or more mycological proven symptomatic episodes during the last 12 months. 12. Inability to comply with the protocol requirements, instructions or study-related restrictions (i.e. uncooperative attitude, inability to return for study visits, unlikelihood of completing the clinical study). 13. Vulnerable patients (i.e. persons kept in detention). 14. Subjects involved in the conduct of the study (i.e. Investigator or his/her deputy, first grade relatives, pharmacist, assistant or other personnel). 15. Participation to an interventional clinical trial within 3 months prior to Visit 0. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Co-primary end-points: microbiological and clinical efficacy of the benzydamine HCl 6 mg and econazole nitrate 150 mg vaginal pessary vs Pevaryl® 150 mg vaginal pessary. · First co-primary end-point: the microbiological response, defined as the absence of Candida or other yeasts at microscopy (mycological cure) at Visit 3, or at Visit 4. · Second co-primary end-point: the clinical response, in terms of the time to first relief of symptoms, defined as the earliest time when the sum of the scores for all symptoms declines by 1 point or more with respect to the sum of the scores at baseline. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The first co-primary endpoint will be evaluated at Visit 3, or at Visit 4. The second co-primary endpoint will be evaluated up to Visit 4. |
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E.5.2 | Secondary end point(s) |
Secondary end-points will be the comparison between the two treatment groups about: · the time to total symptoms relief, defined as the time when the sum of the scores for all symptoms becomes 0; · the clinical response, in terms of percent change of the sum of the scores for all symptoms from baseline at each time point up to Visit 1 (at 24h after the first drug administration), or at ETTV/ETV; · the clinical efficacy, in terms of clinical cure, defined as resolution of all signs and symptoms (total score=0), assessed at Visit 3, or at ETTV/ETV; · the clinical efficacy, in terms of clinical improvement, defined as decrease from baseline of the total score of signs and symptoms ≥50%), assessed at Visit 3, or at ETTV/ETV; · the clinical efficacy in terms of clinical failure, defined as neither resolution nor improvement of all signs and symptoms (total score equal, or <50%, or higher than baseline), assessed at Visit 3, or at ETTV/ETV; · the clinical efficacy, assessed as the sum of the differences of the scores at each time point and baseline for each sign and symptom, estimated as the area under the differences, up to Visit 1 (at 24h after the first drug administration), or up to ETTV/ETV; · the therapeutic cure, assessed as combined mycological and clinical cure at Visit 4 (TOC), or at ETTV/ETV; · the acceptability assessment at Visit 2, or at ETTV; · the recurrent episode of uncomplicated VVC, assessed at the Follow-up Visit; · the safety evaluation. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- the time to total symptoms relief will be evaluated up to Visit 4; - the clinical response will be evaluated up to Visit 1 or at ETTV/ETV; - the clinical efficacy, in terms of clinical cure, clinical improvement and clinical failure will be evaluated at Visit 3, or at ETTV/ETV; - the clinical efficacy, assessed as the sum of the differences of the scores at each time point and baseline for each sign and symptom estimated as the area under the differences, will be evaluated up to Visit 1, or up ETTV/ETV; -the therapeutic cure will be evaluated at Visit 4 or at ETTV/ETV; - the acceptability will be evaluated at Visit 2, or at ETTV; - the safety will be assessed up to Day 23; - the recurrent episode of uncomplicated VVC, assessed at the Follow-up Visit. |
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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 | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | 2 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Bulgaria |
Hungary |
Italy |
Poland |
Russian Federation |
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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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LVLS, including the telephonic follow-up |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 2 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |