Study Comparing SUBA™-Itraconazole With SPORANOX® (Itraconazole) in the Treatment of Onychomycosis

A Randomized, Double Blind, Multiple-site, Placebo-Controlled Study, Comparing the Efficacy and Safety of SUBA™-Itraconazole Capsules Compared to SPORANOX® (Itraconazole) Capsules in the Treatment of Onychomycosis of the Toenail

The objective of this study is to compare the relative efficacy and safety of SUBA™-Itraconazole Capsules (HalcyGen Ltd) to an already marketed oral formulation of itraconazole SPORANOX® (itraconazole) capsules (Janssen Pharma) in the treatment of onychomycosis of the toenail. Both the test and the reference formulations will also be compared to a placebo formulation to test for superiority.

Randomized, Double-Blind, Multiple-Site, Placebo-Controlled, Parallel designed study comparing a dosing regimen of 100 mg approximately 30 minutes prior to breakfast for 12 weeks of SUBA™-Itraconazole 50 mg capsules (HalcyGen Ltd) to the approved dosing regimen of 200 mg taken with breakfast of SPORANOX® (itraconazole) 100 mg capsules (Janssen Pharma). Patients will be randomly assigned in a 3:3:1 ratio to the test product 100 mg once-a-day: reference product 200 mg once-a-day: placebo once-a-day. respectively. The patients will complete 5 visits: baseline/screening (within 28 days of randomization), Day 1 (randomization), Week 6, Week 12 and Week 24.

Inclusion Criteria:

1. Male or non-pregnant, non lactating females 18 years of age or older.
2. Signed informed consent form, which meets all criteria of current FDA regulations.
3. If female and of child bearing potential, have a negative urine pregnancy test at the baseline and randomization visits and prepared to abstain from sexual intercourse or use a reliable method of contraception during the study (e.g., condom with spermicide, inter-uterine device, oral, injected, transdermal or implanted hormonal contraceptives).
4. Clinical diagnosis of onychomycosis of at least one great toenail
5. Clinical signs and symptoms of onychomycosis of the most severely affected great toenail of at least moderate severity as defined by at least 25% but no more than 75% of the most infected toenail and a combined severity score of at least 4 using the Nail Infection Rating Scale (see Appendix A).
6. At least 2mm of clear nail on the most affected toe between the proximal nail fold and the deepest extend of the onychomycosis.
7. Positive potassium hydroxide (KOH) stain for confirmation of fungal nail infection
8. Positive mycological culture for known fungal dermatophyte consistent with onychomycosis infection of at least one of the great toenails.

Exclusion Criteria:

1. Females who are pregnant, lactating or likely to become pregnant during the study.
2. Negative KOH stain
3. Negative mycological culture for fungal dermatophytes consistent with onychomycosis infection.
4. Combined score of less than 4 on the Nail Infection Rating Scale for the most severely affected great toenail.
5. Patient has superficial onychomycosis or significant dystrophy of the target toenail that in the Investigators opinion would impair the evaluation of onychomycosis.
6. Patient has total dystrophic or proximal subungual onychomycosis of the target toenail.
7. Presence of mycotic spikes or patient has exclusively lateral groove involvement of the target toenail.
8. Less than 25% or more than 75% of the most severely infected great toenail affected.
9. Target toenail thickness is greater than 3mm.
10. No new nail growth in the target nail over the previous 6 months.
11. Onychomycosis not caused by a dermatophyte (e.g. mold infection, Candida spp or bacterial infection).
12. Previous treatment for onychomycosis of the toenail within the last 12 months that was unresponsive to treatment.
13. Previous treatment within the previous 2 months with any systemic antifungal therapy or within the previous 2 weeks with any topical antifungal therapy.
14. Significant history or current evidence of chronic infectious disease, system disorder, organ disorder or other medical condition that in the Investigator's opinion would place the study patient at undue risk by participation or could jeopardize the integrity of the study evaluations.
15. Immunocompromised either because of concomitant disease (e.g. HIV), or ongoing treatment (e.g. chemotherapy).
16. Current or history of psoriasis within the previous 12 months.
17. Evidence of ventricular dysfunction such as congestive heart failure (CHF) or a history of CHF.
18. History of diabetes.
19. Previous hypersensitivity to imidazole or azole compounds.
20. Liver Function Test results at screening more than twice the upper limit of normal range or other hematology or clinical chemistry test results that would contraindicate dosing with itraconazole.
21. Use within the previous 3 months or anticipated use during the study of any drugs that are known to affect the bioavailability of oral itraconazole or are otherwise contraindicated to be taken with itraconazole as detailed in the product labeling for SPORANOX® (Appendix B).
22. Receipt of any drug as part of a research study within 30 days prior to dosing.
23. Previous dosing in this study.