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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10030338 |
E.1.2 | Term | Onychomycosis |
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 efficacy of RJ-0265, in terms of complete cure, compared to placebo, for the treatment of toenail onychomycosis due to dermatophyte fungi. |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the efficacy of RJ-0265, in terms of clinical success, responder and improvement, in comparison with placebo at week 52. - To evaluate the efficacy of RJ-0265, in terms of complete cure, in comparison with the marketed reference ciclopirox nail lacquer at week 52. -To evaluate the efficacy of RJ-0265, in terms of clinical success, responder and improvement, compared to marketed reference ciclopirox nail lacquer at week 52. -To assess the growth rate of healthy nail, at week 52. -To assess the time (months) to complete cure or clinical success, at week 52. -To assess all efficacy endpoints at week 48 (end of treatment). -To evaluate the efficacy of RJ-0265, in terms of complete cure, Clinical success and Responders in comparison with placebo at week 52 depending on the baseline degree of involvement
Overall safety of 48 weeks of treatment and follow-up |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent before starting any study related procedures. 2. Adult men and women aged 18 to 75 years with distal mild to moderate onychomycosis due to dermatophyte fungi (i.e. involving > or = 20% to < or = 60% of the distal bed adherent nail plate, without involvement of the lunula) affecting at least one big toenail. 3. Disease proven by culture at screening (positivity confirmed before randomization). 4. Positive Dermatophyte Test Strip (DTS) at screening (positivity confirmed before randomization). In case of negative DTS result, the test can be repeated within 2 weeks. Only when there is a positive result of DTS, the sample will be sent to the central lab for culture. |
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E.4 | Principal exclusion criteria |
1. Allergy to ciclopirox or to any component of the study medication. 2. Life expectancy less than 2 years at screening. 3. Regular use of cosmetic lacquer on the toenails, unwilling to interrupt. 4. Pregnancy or breast-feeding. 5. Woman of child bearing potential who does not use any reliable contraception. 6. Systemic antifungal drugs in the 6 months prior to screening, or need for same. 7. Topical antifungal drugs in the four weeks prior to screening visit. 8. Chemotherapy in the 12 weeks prior to screening or need for same. 9. Immunosuppressive therapy in the 12 weeks prior to screening or need for same. 10. Systemic glucocorticosteroids in the 4 weeks prior to screening or need for same. 11. Systemic antimetabolites in the 4 weeks prior to screening or need for same. 12. Systemic immunostimulants in the 4 weeks prior to screening or need for same. 13. Evidence of psoriasis. 14. Uncontrolled diabetes mellitus (irrespective IDDM, NIDDM). 15. Suspicion or evidence of severe liver or kidney disease. 16. Alcohol or substance abuse. 17. AIDS or any other immunodeficiency. 18. Onychomycosis caused by yeasts or non-dermatophytes moulds. 19. Mucocutaneous candidiasis. 20. White superficial onychomycosis. 21. Proximal subungual involvement (marker of immunosuppressed patient). 22. “Yellow spikes” on nail (extension of fungal infection from distal to proximal part of nail). 23. Patients with recurrent erysipela at the screening (if erysipela infection occur during the study, the patient will be allowed to continue the study and to be treated with antibiotic (penicillin)). 24. Any other medical condition which, in the investigator’s opinion, contraindicates the subject’s participation in the trial. 25. Forecast of little cooperation, non-compliance of medical treatment or little credibility. 26. Has participated in any clinical investigation with medicine within the last 6 months prior to screening visit. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Rate of complete cure, assessed by an independent evaluator, at week 52 (comparison between RJ-0265 and placebo). |
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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) |
- Rate of clinical success as assessed by the independent evaluator at week 52 (comparison between RJ-0265 and placebo) - Rate of responders as assessed by the independent evaluator at week 52 (comparison between RJ-0265 and placebo). - Rate of improvement, as assessed by the independent evaluator, at the end of treatment versus baseline and conversion to negative DTS and culture (comparison between RJ-0265 and placebo). - Decrease of diseased nail area to ≤10% of total, as assessed by the independent evaluator at week 52 (comparison between RJ-0265 and placebo). - Conversion to negative of culture at week 52 (comparison between RJ-0265 and placebo). - Conversion to negative of microscopy findings on DTS examination at week 52 (comparison between RJ-0265 and placebo). - Preliminary assessment of clinical cure, clinical success and responder rate by investigators at week 52. - Growth rate of healthy nail, at week 52. - Diseased nail area by computer planimetry evaluation, after confirmation of independent evaluator (comparison between RJ-0265 and placebo). - Time (months) to complete cure or clinical success as assessed by the independent evaluator and by the investigator. - Rate of complete cure, clinical success and Responders as assessed by the independent evaluator at week 52 (comparison between RJ-0265 and placebo) depending on the baseline degree of involvement (e.g. <30%, <50%, etc.) |
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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 | 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 | No |
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 | No |
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 | Yes |
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 | 5 |
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 | 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 |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |