E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Symptomatic Vaginitis due to Bacterial Vaginosis, Candidiasis or Trichomoniasis |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10062167 |
E.1.2 | Term | Vaginitis bacterial |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10046950 |
E.1.2 | Term | Vaginitis |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10046958 |
E.1.2 | Term | Vaginitis trichomonal |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10048238 |
E.1.2 | Term | Yeast vaginitis |
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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 efficacy on • bacteriological, mycological (candida) and protozoal (Trichomoniasis) infection outcome by culture of vaginal secretion and on • clinical outcome (symptoms)
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E.2.2 | Secondary objectives of the trial |
To assess safety and tolerability |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Female at least 18 yrs old •With a negative urinary pregnancy test before inclusion in the study, •Practicing a reliable contraception method •Patients who are able to understand protocol and have given informed consent •Patients with symptomatic vaginitis e.g: discharge (leucorrhea), itching, burning, irritation, edema, erythema and/or excoriation of the vagina/vulva, painful sexual intercourse (dyspareunia). (Rating: absent = 0; mild = 1; moderate = 2; severe = 3). •Diagnosis of Bacterial vaginosis, candidiasis, or trichomoniasis will be assessed using saline wet mount and potassium hydroxide (KOH) test.
Saline wet mount: Vaginal discharge is placed on a slide with 1-2 drops of 0.9% isotonic sodium chloride solution and examined under high power microscope (x 40). ►Bacterial vaginosis: Saline wet mount is 60% sensitive and 98% specific. Clue cells are vaginal epithelial cells covered with many vaginal rods and cocci bacteria, creating a stippled or granular appearance. A decreased number of lactobacilli are observed, and WBCs are absent. ►Vaginal candidiasis: Hyphae and budding yeast forms are noted. ►T vaginalis infection: Saline wet mount is 80-90% sensitive in symptomatic women. T vaginalis is an oval- or fusiform-shaped protozoan that is 15 mm long (size of a leukocyte), with erratic, twitching motility. A large number of WBCs and epithelial cells are observed.
Potassium hydroxide (KOH) preparation: Vaginal discharge is placed on a slide with 10% KOH solution. Known as the whiff test, a positive finding is the release of a fishy intense amine odor after addition of 10% KOH to discharge. The odor is due to the release of amines such as putrescine, cadaverine, histamine, and trimethylamine.
NB: •Product application during menses should be avoided. •It is recommended that patient should avoid sexual intercourse during the entire study period. •Treatment of the male partner with an appropriate drug is at the discretion of the investigator •Male partners should use condoms during the entire treatment period in order to: (i) Protect the male partner from the effects of the product until the level of female and male epithelial disruption is better known; and (ii) Prevent pregnancy and cross-contamination, although it is expected that women will be relying for contraception
Mixed infections (e.g.: bacteria and candida) confirmed by culture after randomization, and patients with a negative culture at inclusion will remain in the study for safety assessment and sub-group analysis. However, these results will not be used to support the efficacy of any of the three indications.
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E.4 | Principal exclusion criteria |
•Patients who are pregnant. A urinary pregnancy test must be performed before inclusion in the study, •Patients with mixed infections upon clinical and/or microscopic diagnosis, •Patients who are lactating •Patients with liver or renal dysfunction defined as - AST, ALT > 3xULN - serum creatinine >250mol/l •Patients who have other acute gynecological symptoms except for vaginitis (e.g., salpingitis, endometriosis) at the time of screening or admission, •Patients who are unwilling to suspend the use during the study period of other vaginal products such as douches, tampons, spermicides, or herbal preparations, •Patients who have received any other investigational drug within 1 month prior to screening, •Serious medical condition which makes the patients unsuitable for study, •Patients with a concomitant infection that needs an additional antimicrobial agent, •Medical, sociological, or psychological condition which would make the subject unlikely to follow the study protocol, •Inability to undergo repeat treatment, clinical evaluations, and other diagnostic procedures required by the protocol. A patient log and list of all patients screened who were enrolled and who were excluded will be maintained. The reasons for exclusion will be noted.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint: Overall therapeutic cure rate. Therapeutic Cure: A patient who is judged to be both a clinical cure and either a normal bacteriology (+ score) or fungal/ protozoal eradication at Visit 3 (day 21 to 30 of the study)
This composite endpoint is made up of •the clinical cure rate and •the score of cells and bacteria on Gram's stain for BV. •the mycological / protozoal outcome (eradication or persistence) for candidiasis / trichomoniasis
Overall therapeutic cure rate at Visit 3 will be analyzed using a one-sided Chi-Square –test (χ2) for at least one dose group (e.g. the 10 mg dose group).
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | 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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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 | 19 |
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 | Information not present in EudraCT |
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 |
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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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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 | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
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 |