Optimizing the Treatment of Toenail Onychomycosis Using a New Transdermal Patch Combined With Terbinafine/Ketoconazole

This study is currently recruiting participants.
Verified June 2012 by Taiwan Biotech Co., Ltd.
Sponsor:
Information provided by (Responsible Party):
Taiwan Biotech Co., Ltd.
ClinicalTrials.gov Identifier:
NCT01615913
First received: June 4, 2012
Last updated: June 6, 2012
Last verified: June 2012
  Purpose

This study is to explore the optimization of anti‐onychomycosis patch with various formulation contents (three patch groups: 3%, 6% and 8% of terbinafine (contains 3‐mg, 6‐mg and 8‐mg/patch terbinafine, respectively) combined with fixed 2% ketoconazole (contains 2‐mg ketoconazole/patch) and its safety profile.


Condition Intervention Phase
Onychomycosis
Drug: 3 mg terbinafine and 2 mg ketoconazole containing patch
Drug: 6 mg terbinafine and 2 mg ketoconazole containing patch
Drug: 8 mg terbinafine and 2 mg ketoconazole containing patch
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Optimizing the Treatment of Toenail Onychomycosis Using a New Transdermal Patch Combined With Terbinafine and Ketoconazole Formulation

Resource links provided by NLM:


Further study details as provided by Taiwan Biotech Co., Ltd.:

Primary Outcome Measures:
  • Presented by pharmacokinetic data (drug plasma concentrations vs. time) or drug deposit amounts in feet nails. [ Time Frame: baseline, 8-week, 16-week and 24-week ] [ Designated as safety issue: Yes ]
    Both terbinafine and ketoconazole plasma concentration, and their residual contents in toenails will be measured with a validated LC/MS‐MS method.


Secondary Outcome Measures:
  • (1) Efficacy is evaluated 24 weeks after the start of treatment and will be recorded at baseline, 8-week, 16-week and 24-week. [ Time Frame: baseline, 8-week, 16-week and 24-week ] [ Designated as safety issue: Yes ]

    The degrees of improvement are assessed based on each toenail as follows:

    1. Complete cure is defined as regeneration of a healthy nail plate to replace the diseased nail.
    2. Marked improvement is defined as regeneration of a healthy nail plate in at least 70% of the affected nail.
    3. Improvement is defined as regeneration in 40-70% of the affected nail.
    4. Slight improvement is defined as regeneration in less than 40%.
    5. No change is defined as the absence of change or exacerbation of the disease condition or the side effect.

  • (2) Safety Monitoring [ Time Frame: baseline, 8-week, 16-week and 24-week ] [ Designated as safety issue: Yes ]
    Adverse events, both local and systemic, will be recorded and their relation to the trial drugs is judged.


Estimated Enrollment: 18
Study Start Date: April 2012
Estimated Study Completion Date: June 2013
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 3% terbinafine patch
A 10‐cm2 patch containing 3 mg terbinafine and 2 mg ketoconazole
Drug: 3 mg terbinafine and 2 mg ketoconazole containing patch
A novel transdermal patch that is to be used to treat toenail onychomycosis with minimal body exposure to the antifungal drugs. The active substances in the patch are 3% terbinafine (contains 3-mg terbinafine/patch) and 2% ketoconazole (contains 2‐mg ketoconazole/patch). The average daily released drug amount estimated from in‐vitro skin permeation test were about 3.99 mcg for terbinafine and 1.70 mcg for ketoconazole, respectively.
Experimental: 6% terbinafine patch
A 10‐cm2 patch containing 6 mg terbinafine and 2 mg ketoconazole
Drug: 6 mg terbinafine and 2 mg ketoconazole containing patch
A novel transdermal patch that is to be used to treat toenail onychomycosis with minimal body exposure to the antifungal drugs. The active substances in the patch are 6% terbinafine (contains 6-mg terbinafine/patch) and 2% ketoconazole (contains 2‐mg ketoconazole/patch). The average daily released drug amount estimated from in‐vitro skin permeation test were about 8.52 mcg for terbinafine and 2.03 mcg for ketoconazole, respectively.
Experimental: 8% terbinafine patch
A 10‐cm2 patch containing 8 mg terbinafine and 2 mg ketoconazole
Drug: 8 mg terbinafine and 2 mg ketoconazole containing patch
A novel transdermal patch that is to be used to treat toenail onychomycosis with minimal body exposure to the antifungal drugs. The active substances in the patch are 8% terbinafine (contains 8-mg terbinafine/patch) and 2% ketoconazole (contains 2‐mg ketoconazole/patch). The average daily released drug amount estimated from in‐vitro skin permeation test were about 10.7 mcg for terbinafine and 2.17 mcg for ketoconazole, respectively.

Detailed Description:

This study is to explore the optimization of anti‐onychomycosis patch with various formulation contents (three patch groups: 3%, 6% and 8% of terbinafine (contains 3‐mg, 6‐mg and 8‐mg/patch terbinafine, respectively) combined with fixed 2% ketoconazole (contains 2‐mg ketoconazole/patch) and its safety profile. At least 18 patients (age: 20 to 75 years old) with one or two feet toenails infected simultaneously need to complete the whole study. Patients will be assigned to one of patch groups. The patients with only one infected toenail will also apply one patch on other foot with uninfected toenail. The patch will be applied on the foot on the dorsal site and leave it there for two consecutive days. Totally six patches will be used for each week. The duration of therapy will be 24 weeks. The patients' blood sample and toenail clippings will be collected every 8 weeks and will be analyzed as well as the safety profiles. The most appropriate patch formulation will be selected on the drug content residues in toenail. The safety profile will be also presented and discussed with various anti‐onychomycosis patch formulations.

  Eligibility

Ages Eligible for Study:   25 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and females 20‐75 years of age
  • Fungal infection of one or both toenails will be confirmed using the method of histopathological examination with periodic acid‐Schiff (PAS) staining (Yang JH, et al., 2007)
  • The toenail infection can be due to a dermatophyte, yeast or mixed infections (dermatophyte and non‐dermatophyte)
  • The target toenail area must have at least 25% to no more than 75% disease involvement without spikes
  • Patients agree to sign the informed consent form

Exclusion Criteria:

  • Using any kind of systemic or topical nail lacquer solution antifungal drugs within 6 months before at screening visit; or using any other topical antifungal agents, such as ointment, cream, gel, solution, suspension, oil or lotion forms, within two weeks before at screening visits
  • Patients with the target toenail involving the matrix (lunula) or having less than 2 mm clear (unaffected) nail plate length beyond the proximal fold
  • Presence of dermatophytoma on the target nail
  • Using professional pedicures or application of any nail polish product or nail cosmetic to the toenails after the screening visit
  • Patients who are unwilling to provide nail clippings
  • Patients who have been previously reported to be allergic to topical or systemic terbinafine or ketoconazole therapy or both
  • Known pregnancy or plan to get pregnant within study duration or lactation at time of enrollment
  • Unconsciousness or inability to understand this form or this study project.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01615913

Contacts
Contact: Mei-Fang Wen 886-2-2737-2181 ext 3925 985146@h.tmu.edu.tw

Locations
Taiwan
Taipei Medical University Hospital Recruiting
Taipei, Taiwan, 110
Principal Investigator: Woan‐Ruoh Lee, MD         
Sub-Investigator: Hsiou‐Hsin Tsai, MD         
Sponsors and Collaborators
Taiwan Biotech Co., Ltd.
  More Information

No publications provided

Responsible Party: Taiwan Biotech Co., Ltd.
ClinicalTrials.gov Identifier: NCT01615913     History of Changes
Other Study ID Numbers: TE9512
Study First Received: June 4, 2012
Last Updated: June 6, 2012
Health Authority: Taiwan : Food and Drug Administration

Keywords provided by Taiwan Biotech Co., Ltd.:
onychomycosis
terbinafine
ketoconazole
transdermal topical therapy

Additional relevant MeSH terms:
Tinea
Onychomycosis
Dermatomycoses
Skin Diseases, Infectious
Infection
Mycoses
Nail Diseases
Skin Diseases
Ketoconazole
Terbinafine
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014