E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
acute vulvovaginal candidiasis |
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E.1.1.1 | Medical condition in easily understood language |
acute vaginal candida infection |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
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 |
The primary objectives of this study are to evaluate the efficacy of vaginal miconazole nitrate 2% + domiphen bromide cream in the treatment of VVC compared to miconazole nitrate 2% based on the cure rate of VVC at Day 15, and to determine the most optimal dose of domiphen bromide (0.14% or 0.29%) for the treatment of VVC through Week 12.
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to: • Evaluate the safety and tolerability of the two formulations of vaginal miconazole nitrate + domiphen bromide cream through Week 12. • Evaluate the efficacy of vaginal miconazole nitrate + domiphen bromide cream in the treatment of VVC compared to miconazole nitrate 2% based on the cure rate of VVC at Day 29, Day 57 and Day 85. • Evaluate the efficacy of the two formulations of vaginal miconazole nitrate + domiphen bromide treatment on patient reported outcomes through Week 12.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
No separate protocol. 5 eligible patients for the study will enrolled in the PK part of the study. This PK sub-study is not randomized, all 5 patients will receive the miconazole nitrate 2% + domiphen bromide 0.29% treatment for 7 days. They will return on day 7 and 8 for PK blood sampling (just before the last dose as well as 1, 4, 8 and 24h after the last dose), as well as efficacy and safety assessments. On day 85, an additional safety follow-up is performed by telephone. The (exploratory) objective of this PK sub-study is : To assess pharmacokinetics (PK) (ie, area under the concentration-time curve [AUC], clearance [CL], maximum plasma concentration [Cmax], terminal elimination half-life [t½], and time to maximum plasma concentration [Tmax]) of miconazole nitrate and domiphen bromide at Day 7 before and after last application at different time points. |
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E.3 | Principal inclusion criteria |
Subjects must be generally healthy, non-pregnant females 18-50 years of age at Screening Visit. Subjects must have an acute VVC episode at Screening Visit, defined as a total signs and symptoms score of ≥3 and a positive KOH wet mount preparation or Gram stain from a vaginal smear revealing filamentous hyphae/pseudohyphae and/or budding yeast cells. Subjects 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. Subjects of childbearing potential must agree to use highly effective methods of contraception or to abstain from sexual intercourse. |
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E.4 | Principal exclusion criteria |
Subjects with the presence of concomitant vulvovaginitis caused by other pathogens (e.g., bacterial vaginosis, Trichomonas vaginalis, Chlamydia trachomatis, or Neisseria gonorrhoeae) at Screening Visit, or any other infection that requires antibiotic treatment. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy endpoints : • The proportion of subjects with clinical cure at the first follow-up visit (Day 15) • The proportion of subjects with mycological eradication at the first follow-up visit (Day 15) • The proportion of subjects with overall therapeutic success at the first follow-up visit (Day 15)
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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) |
Secondary efficacy endpoints : • The proportion of subjects with clinical cure at the first follow-up visit through Week 12. • The proportion of subjects with mycological eradication at the first follow-up visit through Week 12. • The proportion of subjects with overall therapeutic success (defined as clinical cure and mycological eradication) through Week 12. • Change from Baseline through Week 12 in vulvovaginitis symptom questionnaire total score. • Change from Baseline through Week 12 in the EQ-5D questionnaire total score. Secondary safety endpoints : • Change from Baseline in clinical laboratory parameters on Follow-Up Visits (Serum chemistry, hematology and urinalysis through Week 12) • Frequency and severity of Adverse Events during treatment period as well as post-treatment (AEs) • Change from Baseline in vital signs on Follow-Up Visits through Week 12 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
through Week 12, including follow-up visits on Day 15, Day 29, Day 57 and Day 85 |
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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 | Yes |
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) | 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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | No |
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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The overall End of Study is defined as the LPLV (last patient last visit). |
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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 | |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |