Itraconazole Tablets Vs. Itraconazole Capsules vs. Placebo in Onychomycosis of the Toenail.

• Complete Cure - Itraconazole Tablets Compared to Itraconazole Capsules [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  The primary efficacy endpoint was Compete Cure (consisting of a Clinical Cure and a Mycological Cure) at Month 12. In this study, Clinical Cure was defined as an Investigator's Global Assessment (IGA) score of 0 for the target toenail. Mycological Cure was defined as a negative potassium hydroxide (KOH) examination and a negative culture outcome for dermatophytes of the target toenail. The efficacy analyses were conducted to demonstrate the non-inferiority of 1 itraconazole 200-mg tablet to 2 itraconazole 100-mg capsule.
• Clinical and Mycological Cure of Target Toenail [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  This study was designed to evaluate the superiority of itraconazole tablets to placebo tablets. Clinical Cure was defined as an IGA score of 0 for the target toenail. Mycological Cure was defined as a negative potassium hydroxide (KOH) exam and a negative culture for dermatophytes of the target toenail.

• Investigator’s Global Assessment (IGA) score of the target toenail
• Mycology assessments by KOH and culture for dermatophytes of the target toenail

• Clinical Improvement of the Target Toenail [ Time Frame: 12 months ] [ Designated as safety issue: No ]

  Clinical Improvement consisted of a mycological cure and an Investigator's Global Assessment (IGA) score less than or equal to 1 at Month 12. The Investigator's Global Assessment (IGA) assesses the overall severity of onychomycosis on the target toenail and takes into consideration onycholysis, hyperkeratosis, and percent nail involvement. 0 = Clinical Cure: No evidence of onychomycosis.

  1 = Clinical Improvement: Minimal evidence of onychomycosis. 2 = Mild: ≤25% dystrophy and/or onycholysis. 3 = Moderate: ≤50% dystrophy with onycholysis. 4 = Severe: >50% dystrophy with onycholysis.

• Clinical Improvement Compared to Placebo [ Time Frame: 12 months ] [ Designated as safety issue: No ]

  Clinical Improvement consisted of a mycological cure and an Investigator's Global Assessment (IGA) score less than or equal to 1 at Month 12. The Investigator's Global Assessment(IGA)assesses the overall severity of onychomycosis on the target toenail and takes into consideration onycholysis, hyperkeratosis, and percent nail involvement. 0 = Clinical Cure: No evidence of onychomycosis.

  1 = Clinical Improvement: Minimal evidence of onychomycosis. 2 = Mild: ≤25% dystrophy and/or onycholysis. 3 = Moderate: ≤50% dystrophy with onycholysis. 4 = Severe: >50% dystrophy with onycholysis.

• Number of toenails and fingernails affected with onychomycosis
• Safety and tolerability

Onychomycosis is a common condition accounting for approximately half of all nail disorders. It is most commonly caused by dermatophytes. Itraconazole has been approved for the treatment of onychomycosis in the United States with an approved dosage regimen for the treatment of onychomycosis of the toenail of once daily (QD) treatment with 200mg of itraconazole (two 100 mg capsules) for 12 weeks. Barrier Therapeutics has developed a 200 mg tablet which could be used in a more convenient one-tablet-per-day dosing regimen. This clinical trial will compare the efficacy and safety of this new tablet formulation with itraconazole capsules and placebo.

Onychomycosis is common and accounts for about half of all nail disorders. Usually the cause is due to dermatophytes, either Trichophyton rubrum (71%) or Trichophyton mentagrophytes (20%) but may also be due to yeast infection, usually Candida albicans.

The prevalence of onychomycosis in the United States population as a whole is 13% and is more prevalent in the elderly (60%). Onychomycosis of the toenail recurs and is thought to have a genetic component.

Onychomycosis can result in permanent nail deformity. This disease has a significant impact on the patient's quality of life (e.g., concern with the appearance of the toenails and fingernails, interference with wearing shoes, walking and sports activities).

Itraconazole has been approved for the treatment of onychomycosis in the United States since the mid-nineteen-nineties. The approved dosage regimen for treatment of onychomycosis of the toenail is once daily (QD) treatment with 200 mg of itraconazole (Sporanox®, Janssen Pharmaceutical Products, L.P., Titusville, NJ, USA) for 12 weeks. The approved dosage form is a 100mg capsule. Barrier Therapeutics has developed a 200mg tablet which could be used in a more convenient one-tablet-per-day dosing regimen.

This clinical trial will compare the efficacy and safety of this new tablet formulation with itraconazole capsules and placebo.

• Drug: Itraconazole 100mg capsules
  Subjects took two 100mg capsules once per day after a full meal. The dose dose was taken the day before the Week 12 visit.
  Other Name: Sporanox®
• Drug: Itraconazole 200mg tablets
  Subjects took one 200mg tablet once per day after a full meal. The last dose was taken the day before the Week 12 visit.
  Other Name: Onmel
• Drug: Placebo tablets
  Placebo tablets are the same as the Itraconazole tablets but without the active drug included. Subjects took one tablet once per day after a full meal. The last tablet was taken the day before the Week 12 visit.
  Other Name: placebo

• Experimental: Itraconazole tablets
  Itraconazole 200 mg tablets
  Intervention: Drug: Itraconazole 200mg tablets
• Active Comparator: Itraconazole capsules
  Two Itraconazole 100 mg capsules were taken daily.
  Intervention: Drug: Itraconazole 100mg capsules
• Placebo Comparator: Placebo tablets
  The itraconazole 200-mg tablets and placebo tablets exactly matched one another and were white to slightly grey in color, were oblong and biconvex in shape, and were melt-extrusion, film-coated.
  Intervention: Drug: Placebo tablets

Inclusion Criteria:

• Clinical diagnosis of onychomycosis of at least one great toenail
• Percent Nail Involvement Score of the more severely affected great toenail (the Target Toenail) must be between 2 and 3 (25-75% of the nail unit).
• Length of Unaffected Part of the Target Toenail ≥2mm
• Direct microscopic examination with KOH that is positive for the hyphae associated with dermatophytes on the target toenail
• Subjects must have signed informed consent
• If the subject is woman of childbearing potential, she must have a negative urine pregnancy test and agree to use an effective form of birth control until the first menses after 60 days following the last dose of study medication.

Exclusion Criteria:

• Onychomycosis caused by Candida spp. without the presence of a dermatophyte
• Participation in a clinical trial for the systemic treatment of onychomycosis of the toenail within 24 weeks prior to Visit 1
• Use of systemic antifungals within 12 weeks prior to Visit 1
• Use of topical antifungal nail lacquer within 30 days prior to Visit 1
• Use of any other topical onychomycosis treatment on any toenail within 7 days prior to Visit 1
• Evidence of ventricular dysfunction such as congestive heart failure (CHF) or a history of CHF
• Known liver disease or a history of liver toxicity with other drugs
• Use of systemic immunosuppressants