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

Official Title: “A Phase III Randomized, Evaluator-Blind, Parallel Group Study of the Safety and Efficacy of Itraconazole Tablets, Itraconazole Capsules and Placebo in the Treatment of Onychomycosis of the Toenail.”

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.

Intervention(s) in this Clinical Trial

• 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.
• 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.
• 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.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Itraconazole tablets
  • Itraconazole 200 mg tablets
• Active Comparator: Itraconazole capsules
  • Two Itraconazole 100 mg capsules were taken daily.
• 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.

Primary Measures

• Complete Cure - Itraconazole Tablets Compared to Itraconazole Capsules
  • Time Frame: 12 months
    Safety Issue?: No
• Clinical and Mycological Cure of Target Toenail
  • Time Frame: 12 months
    Safety Issue?: No

Secondary Measures

• Clinical Improvement of the Target Toenail
  • Time Frame: 12 months
    Safety Issue?: No
• Clinical Improvement Compared to Placebo
  • Time Frame: 12 months
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 16 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Stiefel, a GSK Company Industry

Overall Clinical Trial Officials and Contacts

GSK Clinical Trials Study Director GlaxoSmithKline  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00356915

Study ID Number: BT0300-302-INT

ClinicalTrials.gov Identifier: NCT00356915

Health Authority: Canada: Health Canada