The activity of R126638, a new triazole antifungal, as assessed by corneofungimetry

The activity of R126638, a new triazole antifungal, as assessed by corneofungimetry


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TERBINAFINE HAS A BENEFICIAL IMPACT ON PATIENT TREATMENT SATISFACTION IN THE MANAGEMENT OF TOENAIL ONYCHOMYCOSIS Hany Zayed, PhD, Quintiles Strategic Research Services, San Francisco, CA, United States; James Shoffer, DPM, Arrowhead Podiatry, Monika Raut, PhD; Amir Tavakkol, PhD

THE INCREMENTAL DIAGNOSTIC YIELD OF SUCCESSIVE RE-CULTURES IN PATIENTS WITH A CLINICAL DIAGNOSIS OF ONYCHOMYCOSIS Aditya Gupta, MD, PhD, Division of Dermatology, Department of Medicine, Sunnybrook and Women’s College Health Sciences Center (Sunnybrook site) and the University of Toronto, Toronto, ON, Canada, and Mediprobe Research Inc., London, ON, Canada Onychomycosis is a common infection of the nail, affecting up to 30% of the population by age 60 years. In most cases, it is caused by dermatophytes, commonly Trichophyton rubrum and T. mentagrophytes. Accurate diagnosis of dermatophyte infection can provide guidance about the choice of antifungal agent before the initiation of therapy. A choice of techniques is available to confirm the presumptive diagnosis of onychomycosis, with potassium hydroxide (KOH) microscopy and culture being used most frequently. However, KOH microscopy and fungal culture often yield false-negative results. The purpose of this study was to determine the number of times mycology analysis was necessary before nail materials from patients with clinical suspicion of onychomycosis were found to be culture positive. Material from the nails of 1579 patients was obtained for this study and a KOH stain and fungal cultures were performed. The process was repeated up to 4 times if negative cultures resulted. The proportion of positive cultures was calculated based on the total number of cultures processed each time. Our current data showed positive results in 705 of 1579 (44.6%) of the first culture group, 189 of 613 (30.8%) of the second culture group, 91 of 226 (40.3%) of the third culture group, and, of the patients whose nail materials were cultured a fourth time, 21 of 37 (96.8%) were found to be culture positive for a dermatophyte. Overall, 1006 of 1579 (63.7%) of the sample was culture positive for dermatophytes when results of the 4 cultures were combined. These results emphasize the proportion of false-negative results initially obtained using current diagnostic methods for confirming onychomycosis. It is apparent that there is often a need for re-culture in patients clinically suspected of onychomycosis.

Objective: In the treatment of onychomycosis, a patient’s perception of drug effectiveness, ease of administration, and convenience can affect satisfaction and, thus, overall treatment benefi. This study describes and compares satisfaction and convenience of medication use among patients treated for toenail onychomycosis with terbinafine and ciclopirox. Methods: One hundred twenty-six subjects were selected by physicians from 4 private podiatry practices in the United States. Physicians reviewed patient charts to assess medical history and identify patients for inclusion who were previously treated for toenail onychomycosis with either oral continuous-dose terbinafine or topical ciclopirox. All patients in the study were adults who had started treatment from 4 to 12 months before study enrollment. Patients completed a survey questionnaire administered over the telephone by trained interviewers to assess ease and convenience of administration and satisfaction with treatment. Results: Of the126 subjects in the study, 61 had used terbinafine and 65, ciclopirox. The treatment groups differed significantly (P = .02) in both mean age and gender, with the terbinafine group being younger (53.7 vs. 60.1 years) and predominantly male (56.1% vs. 34.5%). As expected, based on package inserts, the length of time that patients used treatment differed significantly (P \.001), with a mean of 2.9 months for the terbinafine group versus 7.2 months for the ciclopirox group. Fewer patients in the terbinafine group had diabetes and poor circulation than in the ciclopirox group (diabetes: 8% vs. 27%; poor circulation: 5% vs. 21% in the terbinafine and ciclopirox groups, respectively). There were statistically significant differences between the two treatment groups with respect to overall satisfaction and convenience. Patients treated with terbinafine were more satisfied than those treated with ciclopirox (63% vs. 32%; P \ .001), and perceived more ease and convenience (56% vs. 30%; P \ .001) with the terbinafine treatment regimen. Adjusted least-square analyses, controlling for group differences in age, gender, and comorbidities, supported the unadjusted findings.

Dr. Gupta has received research grants from, and is on the advisory board and speakers bureau for, Dermik Laboratories. 100% supported by Dermik Laboratories

Conclusions: Patients who used terbinafine for treatment of toenail onychomycosis were more satisfied with their medication and experienced greater ease and convenience than patients who used ciclopirox. These results persisted even after controlling for significant differences in group characteristics. Sponsored by Novartis Pharmaceuticals Corporation

P1831 THE ACTIVITY OF R126638, A NEW TRIAZOLE ANTIFUNGAL, AS ASSESSED BY CORNEOFUNGIMETRY Jannie Ausma, PhD, Barrier Therapeutics NV, Geel, Belgium; Claudine Pie´rardFranchimont, MD, PhD, University Hospital Liege, Lie`ge, Belgium; Marcel Borgers, PhD; Barrier Therapeutics NV, Geel, Belgium Ge´rald Pie´rard, MD, PhD, University Hospital Liege, Lie`ge, Belgium Introduction: R126638 is a novel azole with potent in vitro and in vivo antifungal activity against dermatophytes and yeasts. The objective of the current study was to determine antifungal activity in skin strips of healthy volunteers after intake of R126638 in a daily dose of 100 or 200 mg for 1 week. Method: Two groups of 8 subjects were allocated to 100 or 200 mg of R126638 once daily for 1 week. Five cyanoacrylate skin surface strippings (CSSSs) were obtained from the forearms of each subject before drug intake at day 1 (D1), during treatment at D2 (before drug intake), at D4 (before drug intake), and at D7 (10 hours after drug intake). The posttreatment lingering effect was assessed at D10 (3 days posttreatment) and at D14 (7 days posttreatment). The corneofungimetry bioassay was used to assess the antifungal profile. Cells of different fungal strains (Trichophyton rubrum, Trichophyton mentagrophytes, Microsporum canis, Candida albicans, and Malassezia globosa) were deposited and cultured for 10 days on CSSSs in a sterile and controlled environment. The extent of fungal growth was determined by using computerized image analysis.

P1833 THE SAFETY AND EFFICACY OF 40% UREA GEL IN CONJUNCTION WITH 8% CICLOPIROX LACQUER FOR THE TREATMENT OF ONYCHOMYCOSIS Jenny Sobera, MD, Boni Elewski, MD, University of Alabama at Birmingham, Birmingham, AL, United States

Results: The onset of effects of R126638 was evidenced at D4 when it reached statistical significance for 3 of 5 strains. The reductions at D4 were for C. albicans ÿ31.2% (P = .003), M. globosa ÿ30.2% (P \.001), M. canis ÿ9.8% (P = .105), T. mentagrophytes ÿ26.5% (P = .034), and T. rubrum ÿ32.1% (P = .159). R126638 clearly reduced the percentage of fungi for all tested strains at D7, thereby reaching statistical significance in 4 of 5 strains. The reductions at D7 were for C. albicans ÿ39.0% (P \.001), M. globosa ÿ23.3% (P = .004), M. canis ÿ20.7% (P = .013), T. mentagrophytes ÿ32.5% (P \ .001), T. rubrum ÿ37.0% (P = .093). In the posttreatment period, R126638 exhibited a lingering effect, reaching statistical significance in 4 of 5 strains at D10 (range ÿ18.9% to ÿ36.2%) and at D14 in 2 of 5 strains (range ÿ12% to ÿ21.4%). Conclusion: Data suggest a broad-spectrum activity for R126638 expressed in the skin after oral intake.

The purpose of this investigator-initiated clinical trial is to evaluate the safety and efficacy of the combination of urea 40% gel and ciclopirox 8% nail lacquer in the treatment of onychomycosis. Topical treatment of onychomycosis with 8% ciclopirox lacquer alone has produced cures in fewer than 10% of patients. It is theorized that the application of urea before the application of ciclopirox will aid in thinning and debulking the thick, hyperkeratotic nail, therefore allowing better penetration of the antifungal agent into the nail plate and increasing its efficacy. Increased efficacy of topical therapies for onychomycosis could allow decreased reliance upon potentially toxic oral antifungals for treatment of this common infection. We will present the results of this investigator-initiated, double-blind pilot study that included 32 subjects with potassium hydroxideepositive toenail onychomycosis. The subjects were randomized into one of three treatment groups. They applied gel (vehicle or active 40% urea) to a target diseased nail every morning and lacquer (vehicle or active 8% ciclopirox) to the same nail every night. Ten participants received both active urea 40% gel and active ciclopirox 8% nail lacquer. Ten subjects received active urea gel and inactive lacquer vehicle. Ten were given inactive gel vehicle and active ciclopirox lacquer. All groups were instructed to apply the medication over the medications applied the previous day. At the end of each week, they were asked to remove the medications from the nail with 70% isopropyl alcohol. This cycle was continued for 6 months. Each participant was evaluated every 4 weeks throughout the treatment phase. A follow-up evaluation was conducted 12 weeks after completion of the treatment phase.

100% supported by Barrier Therapeutics

Supported by Bradley Pharmaceuticals (cost of poster)

MARCH 2005