Efficacy Safety, and Tolerability of Topical Terbinafine in Patients With Mild to Moderate Toenail Fungus of the Big Toenail

A Randomized, Double-blind, Vehicle-controlled, Multicenter, Parallel Group Study to Assess the Efficacy, Safety, and Tolerability of Topical Terbinafine Hydrogen Chloride (HCl) Formulation for 24 or 48 Weeks of Treatment in Patients With Mild to Moderate Toenail Onychomycosis

This study is designed to assess the efficacy, safety and tolerability of a topical formulation of terbinafine solution applied daily in patients with toenail fungus. This trial will study patients with mild to moderate toenail fungus disease of the big toenail and their responses to two treatment durations, 24 or 48 weeks.

Study Overview

• Status: Completed
• Conditions: Onychomycosis
• Intervention / Treatment: Drug: terbinafine; Drug: terbinafine; Drug: Placebo; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 526
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Various Cities, France
    • Novartis Investigative Site
• Germany
  • Investigative Site, Germany
    • Novartis
  • Various cities, Germany
    • Novartis Investigative Site
• United States
  • California
    • Novato, California, United States, 94945
      • Dr. Fred D. Youngswick
  • Colorado
    • Northglenn, Colorado, United States, 80234
      • Dr. Larry Doehring
  • Florida
    • Melbourne, Florida, United States, 32935
      • Dr. Robert P. Dunne
  • Georgia
    • Newnan, Georgia, United States, 30263
      • Dr. Mark Ling
  • Illinois
    • Chicago, Illinois, United States, 60632
      • Dr. Jesse Plasencia
  • Kansas
    • Overland Park, Kansas, United States, 66215
      • Dr. John Mallory
    • Topeka, Kansas, United States, 66606
      • Dr. Jeffrey Conrow
  • Louisiana
    • Covington, Louisiana, United States, 70433
      • Dr.Michael Kaye
  • Maryland
    • Baltimore, Maryland, United States, 21214
      • Dr. Max Weisfeld
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Dr. Linda Stein-Gold
  • Missouri
    • St. Louis, Missouri, United States, 63104
      • Dr. Anna Glaser
  • New York
    • New York, New York, United States, 10032
      • Dr. Richard Scher
  • North Carolina
    • Winston Salem, North Carolina, United States, 27157
      • Dr. Joseph Jorrizo
  • Ohio
    • Cincinnati, Ohio, United States, 45230
      • Dr. Anne Lucky
  • Oregon
    • Portland, Oregon, United States, 97210
      • Dr. Rich Phoebe
  • South Carolina
    • Simpsonville, South Carolina, United States, 29681
      • Dr. Patricia Westmorland
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Dr. David Horowitz
  • Texas
    • Irving,, Texas, United States, 75061
      • Dr. Jay Lifshen
    • San Antonio, Texas, United States, 78229
      • Dr. Richard Pollak
  • Virginia
    • Virginia Beach, Virginia, United States, 23464
      • Dr. Patrick Agnew

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and females 12 - 75 years of age
• Fungal toenail infection of one or both of the large (great) toenails
• The nail infection must be due to a dermatophyte, (mixed infections dermatophyte and non-dermatophyte] are not allowed)

Exclusion Criteria:

• Target foot must not have severe plantar (moccasin) tinea pedis that would require systemic therapy. Mild to moderate tinea pedis (athlete's foot) infection should be treated with terbinafine prior to baseline or at any time during the trial. Other topical treatments for athlete's foot may be recommended at the discretion of the investigator.
• Subjects must not have abnormalities of the nail that could prevent a normal appearing nail if clearing of infection is achieved
• No administration of systemic antifungal medications within 6 months prior to screening visit
• No application of prescription topical antifungal medications for toenail fungus within 3 months or other commercially available topical medications for toenail fungus applied directly to the toenails within 1 month prior to screening visit
• No professional pedicures or application of any nail polish product or nail cosmetic to the toenails after the screening visit
• Known pregnancy or lactation at time of enrollment

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) for 48 weeks	Drug: terbinafine; Terbinafine hydrochloride (HCl) 10 % nail solution for onychomycosis (NSO) once daily for 48 weeks; Other Names: Lamisil; Drug: terbinafine; Terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis once daily for 24 weeks; Other Names: Lamisil
Placebo Comparator: 2; Vehicle (placebo) for 48 weeks	Drug: Placebo; Vehicle (placebo) once daily for 48 weeks; Drug: Placebo; Vehicle (placebo) once daily for 24 weeks
Experimental: 3; Terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis (NSO) for 24 weeks	Drug: terbinafine; Terbinafine hydrochloride (HCl) 10 % nail solution for onychomycosis (NSO) once daily for 48 weeks; Other Names: Lamisil; Drug: terbinafine; Terbinafine hydrochloride (HCl) 10 % Nail Solution for Onychomycosis once daily for 24 weeks; Other Names: Lamisil
Placebo Comparator: 4; Vehicle (placebo) for 24 weeks	Drug: Placebo; Vehicle (placebo) once daily for 48 weeks; Drug: Placebo; Vehicle (placebo) once daily for 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy Assessed by the Percentage of Participants With Complete Cure at the End of Study (Week 52) After Treating for 24 or 48 Weeks	Complete cure is defined as negative KOH microscopy and negative culture for dermatophytes and no residual involvement of the target toenail.	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy Assessed by the Percentage of Participants With Mycological Cure at the End of Study After Treating Participants for 24 or 48 Weeks	Mycological cure is defined as negative KOH microscopy and negative culture for dermatophytes.	52 weeks
Efficacy Assessed by the Percentage of Participants With Clinical Effectiveness at the End of Study After Treating Participants for 24 or 48 Weeks	Clinical effectiveness is defined as negative KOH microscopy and negative culture for dermatophytes and <= 10% residual involvement of the target toenail. Clinical effectiveness was a composite binary variable defined as "Yes" if: If mycological cure (negative KOH and negative culture for dermatophytes) and; = 10% residual involvement of the target toenail "No" if otherwise	52 weeks
Safety and Tolerability Assessed by the Number of Participants With Adverse Events	Safety and tolerability data as assessed by the number of participants with Adverse Events (AE), Serious Adverse Events, Drug discontinuation due to an AE and death. Additional details can be found in the Adverse Event Section.	52 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): June 1, 2008
• Study Completion (Actual): June 1, 2008

Study Registration Dates

• First Submitted: March 2, 2007
• First Submitted That Met QC Criteria: March 5, 2007
• First Posted (Estimate): March 6, 2007

Study Record Updates

• Last Update Posted (Estimate): April 19, 2011
• Last Update Submitted That Met QC Criteria: March 22, 2011
• Last Verified: March 1, 2011

More Information

Terms related to this study

• Keywords: Onychomycosis; Dermatophytes; Toenail fungus; Nail fungus; Toenail fungal infection; Tinea unguium; Foot dermatoses
• Additional Relevant MeSH Terms: Skin Diseases; Infections; Bacterial Infections and Mycoses; Skin Diseases, Infectious; Mycoses; Tinea; Dermatomycoses; Nail Diseases; Onychomycosis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antifungal Agents; Terbinafine
• Other Study ID Numbers: CSFO327N2302