Bilateral onychomycosis of the hallux nail (great toe) with positive mycosis culture and KOH microscopy as per central laboratory, otherwise healthy according to physical examination MedDRA version: 9.1 Level: PT Classification code 10030338 Term: Onychomycosis
Conditions
Interventions
Product Name: 067 (terbinafine in Transfersome®)
Product Code: 067
Pharmaceutical Form: Cutaneous suspension
INN or Proposed INN: terbinafine hydrochloride
CAS Number: 78628-80-5
Current Sponsor code
Sponsors
CPDS BERMUDA, LTD.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Informed consent signed and dated • Bilateral onychomycosis of the hallux nail (great toe) with positive mycosis culture and KOH microscopy as per central laboratory of at least one hallux, otherwise healthy according to physical examination • At least 2 mm of the proximal hallux nail not affected by onychomycosis • male and female patients • Aged over 18 years • Reliable method of contraception for women of childbearing potential (i.e. low failure rate less than 1% per year) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: General Exclusion Criteria •Participation in a clinical study within 30 days prior to screening •Pregnancy or lactation •Subjects who are inmates of psychiatric wards, prisons, or other state institutions •Previously allocated to this study •Directly or indirectly involved in the conduct and administration of this study (i.e., principal investigator, sub-investigator, study co-ordinators, other study staff, employees of IDEA AG, IDEA AG contractors, and the families of each). Medical History Related Exclusion Criteria •Treatment with pharmaceuticals containing terbinafine during the past 52 weeks before start of treatment •Treatment with other antimycotics during the past 8 weeks before start of treatment •History of dermal allergic reactions to pharmaceutical or cosmetic products •History of hypersensitivity or allergy to terbinafine •History of liver or kidney failure •History of Diabetes mellitus •Immunodeficienca inc. HIV infection •Mental disorders •Drug or alcohol dependency •Surgery 4 weeks prior to visit 1 •Laboratory abnormalities as described for individual discontinuation criteria Indication specific Exclusion Criteria •Treatment with other antimycotics during the study •Infections in target area Prohibited Concomitant Medication/Therapy •Any nail clipping of the nail (target area) from the start of treatment until end of study visit (week 48) •Any concomitant medication which might influence the study objectives or interfere with the CYP2D6 metabolism, e.g. b-blocker, MAO-inhibitors, antidepressants until week 14 (visit 5) •Concomitant use of pharmaceuticals containing terbinafine during the study •Concomitant use of other antimycotics during the study •The target area must not be treated with other topical dermatics (including cosmetic products) •any blood or plasma donation during treatment period up to visit 5
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •Mycological cure rate after 12 weeks of treatment with 067 (sampling at week 14);Secondary Objective: •Clinical cure rate after 24 and 48 weeks (12 weeks of treatment with 067, 3 mg terbinafine per target area and application, twice daily, 12 and 36 weeks of untreated follow-up) •Effect on clinical disease activity at week 24 and 48 •Mycological cure rate at week 48 •Pharmacokinetics after single-dose application and at steady state •Systemic and local safety of 067 (total daily dose: 12 mg terbinafine per day) ;Primary end point(s): Primary: •Mycological cure rate defined by KOH microscopy and mycological culture at week 14 (after 12 weeks of treatment) Secondary: •Clinical cure rate defined by normal growth of toe nail of at least 2 mm after 24 weeks and at least 5 mm after 48 weeks. •Clinical disease activity defined by assessing the parameters onycholysis, subungual hyperkeratosis, discoloration and thickening of the nail •Mycological cure rate defined by KOH microscopy and mycological culture at week 48 •Plasma level of active ingredient (terbinafine) prior to first and last application and 14±3 days after discontinuation in complete population •Level of active ingredient (terbinafine) in nail clippings •Determination of pharmacokinetics: plasma level of active ingredient (terbinafine) prior to and 0.5, 1, 2, 4, 8 and 12 hours after first application, and plasma level of active ingredient (terbinafine) prior to and 0.5, 1, 2, 4, 8, 12, 24, 48 hours and 14±3 days after last application in a subpopulation (see 8.2.3) Local safety assessed by •Dermatological evaluation of the target areas, i.e. irritation, redness, swelling or inflammation •Recording of local adverse events throughout the study Systemic safety assessed by •Physical examination •Recording of systemic adverse events throughout the study •Safety laboratory parameters (For local and systemic evaluation, please see section 9.1. of the clinical trial protocol.) | — |
Countries
Germany
Outcome results
None listed