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

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.

Study Overview

• Status: Completed
• Conditions: Onychomycosis
• Intervention / Treatment: Drug: Itraconazole 200mg tablets; Drug: Itraconazole 100mg capsules; Drug: Placebo tablets

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 1381
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2S3B3
      • Dr. Kirk Barber
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z3Y1
      • Dr. Richard Thomas
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C8X3
      • Dr. Marc Bourcier
  • Ontario
    • London, Ontario, Canada, N5X2P1
      • Dr. Aditja Gupta
    • Markham, Ontario, Canada, L3P7N8
      • Dr. Chuck Lynde
    • Oakville, Ontario, Canada, L6K1E1
      • Entralogix
    • Windsor, Ontario, Canada, N8W5L7
      • Dr. Jerry Tan
  • Quebec
    • Montreal, Quebec, Canada, H2K4L5
      • Dr. Robert Bissonnette
• Dominican Republic
  • Santo Domingo, Dominican Republic
    • Edifico Professional Guarionex Lopez
• Ecuador
  • Guayaquil, Ecuador
    • Dr. Manuel Briones
• Honduras
  • Sula
    • San Pedro, Sula, Honduras
      • Centro Orquidea Blanca
• Panama
  • Panama City, Panama
    • Clinica Metropolis II
• South Africa
  • Cape Town, South Africa
    • University of Cape Town
  • Cape Town, South Africa
    • Langeberg Medical Centre
  • Durban, South Africa
    • Dr. Z. F. Ahmed Vawda
  • Krugerson, South Africa
    • DJW Navorsing
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Radiant Research -Birmingham
    • Birmingham, Alabama, United States, 35233
      • University of Alabama School of Medicine
  • Arizona
    • Tuscon, Arizona, United States, 85710
      • Radiant Research - Tucson
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • Burke Pharmaceutical Research
  • California
    • Fremont, California, United States, 94538
      • East Bay Dermatology Medical Group Inc.
    • San Diego, California, United States, 92123
      • Therapeutics Clinical Research
    • San Diego, California, United States, 92117
      • Skin Surgey Medical Group
    • San Francisco, California, United States, 94143-0517
      • University of California
    • Santa Rosa, California, United States, 95405
      • Radiant Research - Santa Rosa
  • Colorado
    • Englewood, Colorado, United States, 80112
      • Meridian Skincare
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • The Savin Center
  • Florida
    • Aventure, Florida, United States, 33180
      • Dr. Stephen Horwitz
    • Miami, Florida, United States, 33144
      • International Dermatology Research Inc.
    • Miami, Florida, United States, 33175
      • FMX Research Corporation
    • Ormond Beach, Florida, United States, 32174
      • Advanced Dermatology and Cosmetic Surgery
    • St. Petersburg, Florida, United States, 33781
      • Radiant Research - St. Petersburg
    • West Palm Beach, Florida, United States, 33407
      • Radiant Research - West Palm Beach
  • Georgia
    • Austell, Georgia, United States, 30106
      • Radiant Research - Atlanta West
    • Snellville, Georgia, United States, 30078
      • Gwinnett Clinical Research Center Inc.
  • Idaho
    • Boise, Idaho, United States, 83704
      • Northwest Clinical Trials
  • Illinois
    • Chicago, Illinois, United States, 60610
      • Radiant Research - Chicago
  • Kansas
    • Overland Park, Kansas, United States, 66215
      • Radiant Research - Kansas City
  • Michigan
    • Ann Arbour, Michigan, United States, 48103
      • Dr. David Fivenson
    • Troy, Michigan, United States, 48083
      • Skin and Vein Center
  • Minnesota
    • Fridley, Minnesota, United States, 55432
      • Minnesota Clinical Study Center
    • Minneapolis, Minnesota, United States, 55417
      • VA Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • Dr. Eduardo Tschen
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10021
      • Skin Specialty Group
  • North Carolina
    • High Point, North Carolina, United States, 27262
      • Dermatology Consulting Services
  • Ohio
    • Cincinnati, Ohio, United States, 45249
      • Radiant Research - Cincinnati
    • Cincinnati, Ohio, United States, 45219
      • Dermatology Clinical Research Center
  • Oregon
    • Portland, Oregon, United States, 97223
      • Oregon Medical Research Center
    • Portland, Oregon, United States, 97210
      • Northwest Cutaneous Research
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Radiant Research - Anderson
    • Greenville, South Carolina, United States, 29617
      • Radiant Research - Greenville
    • Greer, South Carolina, United States, 29651
      • Dr. J. M. Humeniuk
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Dermatology East
    • Knoxville, Tennessee, United States, 37917
      • Dermatology Associates of Knoxville
    • Nashville, Tennessee, United States, 37215
      • Tennessee Clinical Research Center
  • Texas
    • Austin, Texas, United States, 78759
      • DermResearch Inc.
    • Bryan, Texas, United States, 77802
      • Dr. Terry Jones
    • Dallas, Texas, United States, 75231
      • Radiant Research - Dallas North
    • San Antoinio, Texas, United States, 78229
      • Dr. Stephen Miller
    • San Antonio, Texas, United States, 78229
      • Endeavor Clinical Trials
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • Dermatology Research Center
    • West Jordan, Utah, United States, 84088
      • South Valley Dermatology Center
  • Virginia
    • Norfolk, Virginia, United States, 235507
      • Pariser Dermatology Specialists Ltd.
  • Washington
    • Tacoma, Washington, United States, 98499
      • Radiant Research - Tacoma
  • Wisconsin
    • Madison, Wisconsin, United States, 53719
      • Madison Skin and Research Inc.
    • Milwaukee, Wisconsin, United States, 53209
      • Advanced Healthcare S. C.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 73 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Itraconazole tablets; Itraconazole 200 mg tablets	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 Names: Onmel
Active Comparator: Itraconazole capsules; Two Itraconazole 100 mg capsules were taken daily.	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 Names: Sporanox®
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.	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 Names: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical and Mycological Cure of Target Toenail	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.	1 year
Complete Cure - Itraconazole Tablets Compared to Itraconazole Capsules	The primary efficacy endpoint was Compete Cure (consisting of a Clinical Cure and a Mycological Cure) at week 52. 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.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Improvement of the Target Toenail	Clinical Improvement consisted of a mycological cure and an Investigator's Global Assessment (IGA) score less than or equal to 1 at week 52. 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.	12 months
Clinical Improvement Compared to Placebo	Clinical Improvement consisted of a mycological cure and an Investigator's Global Assessment (IGA) score less than or equal to 1 at week 52. 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.	12 months

Collaborators and Investigators

• Sponsor: Stiefel, a GSK Company
• Collaborators: GlaxoSmithKline

Publications and helpful links

General Publications

• Maddin S, Quiring J, Bulger L. Randomized, placebo-controlled, phase 3 study of itraconazole for the treatment of onychomycosis. J Drugs Dermatol. 2013 Jul 1;12(7):758-63.

Study record dates

Study Major Dates

• Study Start: July 1, 2006
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: July 25, 2006
• First Submitted That Met QC Criteria: July 25, 2006
• First Posted (Estimate): July 27, 2006

Study Record Updates

• Last Update Posted (Estimate): February 9, 2017
• Last Update Submitted That Met QC Criteria: December 16, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: Onychomycosis; Itraconazole; Nail fungus; Toenail
• Additional Relevant MeSH Terms: Skin Diseases; Infections; Bacterial Infections and Mycoses; Skin Diseases, Infectious; Mycoses; Tinea; Dermatomycoses; Nail Diseases; Onychomycosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Itraconazole; Hydroxyitraconazole
• Other Study ID Numbers: BT0300-302-INT