Detection and relevance of naftifine hydrochloride in the stratum corneum up to four weeks following the last application of naftifine cream and gel, 2%.

BACKGROUND: Two-week treatment using naftifine cream or gel, 2% has been shown to be efficacious in subjects with Tinea pedis and/or Tinea cruris, and in most cases, continued improvement has been observed following cessation of treatment for up to four weeks. One possible explanation for continuous post-treatment improvement is drug-levels remaining in the stratum corneum (SC) as a function of time. OBJECTIVE: The objective is to use tape stripping methodology to assess the amount of drug available in the SC over a 28 day period following the last dose. METHODS: This was an open-label, single-exposure study on subjects comparing the amount of drug that was absorbed into the SC following topical application for 2-weeks. Twelve subjects were dosed daily (6 with naftifine cream, 2% and 6 with naftifine gel, 2%). Subjects had twelve 8 cm2 test application sites demarcated on the upper back. Twenty-five individual sequential strips were obtained from each test site. Of these, 11 sites were dosed once daily with the drug (5.0µL/cm2) for days 1 to 14 and the final site served as the control. On days 15, 29, and 43, a site was stripped to collect the SC in order to process the amount of drug present. RESULTS: Naftifine was present on all tape strip samples collected over the 28 day period following two weeks of application. Furthermore, the most relevant, deeper tape strip sets reflecting the SC, showed potentially clinically relevant presence of naftifine in the skin for 28-days post-treatment. CONCLUSIONS: Naftifine was present in the tape strips on all sample collection days up to and including four weeks following the last drug application. These findings help explain the progressive improvement in clinical and mycological response rates during the treatment period and for up to four weeks post-treatment in the clinical trials using naftifine.

Efficacy and safety of naftifine HCl Gel 2% in the treatment of interdigital and moccasin type tinea pedis: pooled results from two multicenter, randomized, double-blind, vehicle-controlled trials.

BACKGROUND: Tinea pedis is the most common chronic fungal infection. Naftifine hydrochloride is a topical antifungal of the allylamine class, displaying fungicidal activity and clinically significant anti-bacterial and anti-inflammatory effects. OBJECTIVE: To evaluate the efficacy and safety of two-weeks once daily application of naftifine gel 2% in the treatment of tinea pedis. METHODS: At baseline, 1715 subjects were randomly assigned 2:1 to naftifine gel 2% (n=1144) and vehicle (n=571). Efficacy consisting of mycologic determination (KOH and dermatophyte cultures) and scoring of clinical symptom severity was evaluated at baseline and weeks 2, 4, and 6. Efficacy was analyzed in 1174 subjects (n=782, naftifine; n=392, vehicle) with a positive baseline dermatophyte culture and KOH for whom week 6 assessments were available. Safety was evaluated by adverse events (AE) and laboratory values in 1714 subjects (n=1143, naftifine; n=571, vehicle). RESULTS: Subjects treated with naftifine gel 2% for interdigital-type tinea pedis demonstrated greater improvement from baseline for complete cure (P=0.001), mycological cure (P<0.0001), and treatment effectiveness (P<0.0001) as early as 2 weeks when compared to vehicle; however the highest response rates were seen 4-weeks post treatment (P<0.0001, for all endpoints). Statistically significant results for complete cure, mycological cure, and treatment effectiveness (P<0.0001, for all endpoints) were also seen at week 6 among subjects with moccasin-type tinea pedis. Treatment related adverse events were minimal. CONCLUSIONS: Treatment with naftifine gel 2% applied once daily for two weeks is well-tolerated and is effective in treating both interdigital-type and moccasin-type tinea pedis. Continuous improvement is observed from the end of treatment to four-weeks after treatment cessation among key outcome measures (complete cure, mycological cure, and treatment effectiveness) as well as clinical signs and symptoms (erythema, scaling, and pruritus)

A new proprietary onion extract gel improves the appearance of new scars: a randomized, controlled, blinded-investigator study.

OBJECTIVE: This randomized, controlled, single-blind study evaluated the appearance of new dermal scars after eight weeks of once-daily application of a nonprescription proprietary onion extract gel formulation compared to control (no application scars) in a dermatological surgical setting. METHODS: At Visit 1, 44 healthy male and female subjects aged 18 to 70 years gave informed consent, were screened, and enrolled in the study. Two bilateral, 8mm seborrheic keratoses, one on the right and one on the left chest, were surgically removed from each subject. The wounds were photographed at all visits. Two weeks later (Visit 2), each subject was randomly assigned to apply onion extract gel to either the right or left side wound site once daily for eight weeks and no treatment on the opposite wound. The investigator was blinded to which wound was treated. At two, four, and eight weeks after gel application, right and left scars were graded by the investigator and subjects for improvement from baseline in overall appearance, texture, redness, and softness using 4-point ordinal scales (0=no improvement, 1=mild improvement; 2= moderate improvement; 3=significant improvement). Safety was evaluated by adverse events. RESULTS: Six subjects (13.6%) experienced mild stinging that resolved spontaneously. At two weeks, the subjects rated gel-applied scars to be significantly softer than control scars (p=0.014). After four and eight weeks of application, the investigator and subjects rated all appearance variables of the gel-applied scars to be significantly more improved from baseline than control scars (p=0.017 to p<0.01). CONCLUSION: The new proprietary onion extract gel is safe and significantly improves scar appearance after four weeks of once-daily application.

An open-label pilot study of naftifine 1% gel in the treatment of seborrheic dermatitis of the scalp.

Topical antifungal treatment is a mainstay of therapy for Seborrehic Dermatitis (SD). Although the amidazole and ciclopyridine antifungals have been extensively studied, few clinical efficacy data are available for topical allylamine therapy in SD. The objective of this open-label exploratory study was to evaluate the efficacy and safety of natifine HCl 1% gel applied twice daily for 4 weeks, as topical treatment of moderate SD of the scalp. Nine subjects (5 men, 4 women) with a mean age of 56 (33-81) years with SD of the scalp were enrolled and made 4 visits to the site. At Visit 1 (Week 0), subjects were screened, enrolled, baseline efficacy data were obtained, and treatment was initiated. Subjects returned at Week 2, Week 4 (end of treatment), and Week 6 for efficacy and safety assessments. Efficacy was evaluated by changes from baseline in investigator-rated scores on 0-5-grade scales: (1) SD Global Evaluation Scale (SDGES), (2) Erythema Severity Scale, (3) Scaling Severity Scale, (4) % Scalp Involvement Scale, and subject-rated scores on the (4) Itching Severity Scale, and (5) Global Improvement Scale, where 0=none and 5=most severe. Mean severity scores for the SDGES and % Scalp Involvement scales progressively declined (improved) 66% and 54% from respective baseline levels at Week 6. Mean erythema rating decreased 38% from baseline and scaling decreased 50% from baseline by Weeks 4 and 6. Itching improved in 5 of 9 (56%) subjects by the end of treatment. A total of 8 of 9 (89%) subjects rated their symptoms as improved from baseline at the end of treatment and Week 6. There were no treatment-related adverse events during the study. These results suggest that naftifine 1% gel applied twice daily for 4 weeks is effective and safe topical treatment for moderate SD of the scalp.

An open-label study of naftifine hydrochloride 1% gel in the treatment of tinea versicolor.

Tinea versicolor (TV) is a superficial cutaneous fungal infection characterized by cutaneous pigment changes, pruritus, scaling, and erythema. This open-label, single-center pilot study evaluated the efficacy and safety of naftifine 1% gel applied twice daily for 2 weeks in 10 men and women (median age 38 years) with TV. Baseline mycology status was determined by potassium hydroxide (KOH) and microscopy and clinical symptom severity (CSS) scored by the investigator using a 0 to 9 scale (0=absent, 9=worst). Patients applied naftifine HCI 1% gel to the affected area twice daily for 14 days. They returned for follow-up efficacy and safety assessments at the end of treatment (week 2), 2 weeks after treatment (week 4), and 6 weeks after treatment (week 8). All patients had a positive mycology at baseline; one was KOH negative at week 2, two were negative at week 4, and five (50%) were negative at week 8. Mean investigator total CSS score decreased from a baseline value of 4.7 to 3.2 at week 2 (32% improvement), 2.6 at week 4 (45% improvement), and 2.7 at week 8 (43% improvement). The patients rated their symptoms to be improved at all follow-up visits. There were no treatment-related adverse events during the study. These results suggest that naftifine 1% gel is a safe and efficacious topical treatment for TV.

A randomized, double-blind, vehicle-controlled efficacy and safety study of naftifine 2% cream in the treatment of tinea pedis.

OBJECTIVE: Naftifine HCl 2% cream (NAFT-2) is a topical allylamine antifungal agent under development in the United States. This randomized, double-blind, vehicle-controlled, phase 3 trial evaluated the efficacy and safety of two weeks of NAFT-2 treatment in subjects with tinea pedis. Naftifine 1% cream (NAFT-1) treatment for four weeks and vehicle were also evaluated as a positive control. METHODS: 709 subjects were randomly assigned 2:1:2:1 to one of four treatment groups: (i) NAFT-2 (n= 235), (ii) two-week vehicle (n=118), (iii) NAFT-1 (n=237), or (iv) four-week vehicle (n=119). Efficacy was evaluated at baseline, week 2, week 4, and week 6 and consisted of mycology determination (KOH and dermatophyte culture) and scoring of clinical symptom severity (erythema, scaling, and pruritus). Efficacy was only analyzed in 425 subjects with positive baseline dermatophyte culture. Safety was evaluated by adverse events (AE) and laboratory values in 707 subjects. RESULTS: At week 6, NAFT-2 subjects achieved 18 percent complete cure rate, 67 percent mycological cure rate, 57 percent treatment effectiveness, 22 percent clinical cure rate, and 78 percent clinical success rate compared to respective vehicle rates of seven percent (one-sided, P<0.01), 21 percent (P<0.001), 20 percent (P<0.001), 11 percent (P=0.04) and 49 percent (P<0.001). Week 6 efficacy responses in NAFT-1-treated subjects were significantly higher than vehicle subjects and almost identical to NAFT-2 subjects. Mycological cure and clinical response rates in both NAFT-2 and NAFT-1 increased from week 2 to week 6. Treatment-related AEs occurred in five percent of NAFT-2 subjects, seven percent of vehicle subjects, four percent of NAFT-1 subjects and eight percent of vehicle subjects. The most common AEs for all groups were application site pruritus and skin irritation. CONCLUSION: Topical NAFT-2 for two weeks is safe and provides significantly superior antifungal treatment than vehicle in tinea pedis subjects. NAFT-2 produces equivalent efficacy responses to four weeks of NAFT-1 treatment. The fungicidal activity of naftifine continues to increase for at least one month after treatment is completed. (Clinical Trials Identification Numbe=NCT00750139). J Drugs Dermatol. 2011;10(11):1282-1288.

A double-blind, randomized, vehicle-controlled study evaluating the efficacy and safety of naftifine 2% cream in tinea cruris.

OBJECTIVE: Naftifine HCl 2% cream (NAFT-2%) is a topical allylamine antifungal preparation under development in the U.S. The objective of this randomized, double-blind, vehicle-controlled study was to evaluate the efficacy and safety of a two-week course of once-daily NAFT-2% vs. vehicle in the treatment of Tinea cruris ("jock itch"). METHODS: A total of 334 subjects with T. cruris were enrolled and randomly assigned to NAFT-2% (n=166) or vehicle (n=168), which was applied once daily for 14 days. Efficacy and safety were evaluated at week 2 (end of treatment) and week 4. Efficacy measures included complete cure, treatment effectiveness, mycological cure, clinical cure, and clinical success and were analyzed only in subjects with a positive potassium hydroxide (KOH) and dermatophyte culture at baseline (n=75, naftifine; n=71, vehicle). Safety was assessed by adverse events and changes from baseline in clinical status and laboratory studies. RESULTS: At week 4, 25 percent of naftifine-treated subjects achieved complete cure vs. three percent of vehicle subjects and 72 percent achieved mycological cure vs. 16 percent of vehicle treated subjects (one-sided, P<0.001). Treatment effectiveness was achieved in 60 percent of NAFT-2% subjects vs. 10 percent of vehicle subjects (one-sided, P<0.001). Clinical cure rate and clinical success rate were 33 percent and 84 percent in NAFT-2% subjects, respectively vs. 10 percent and 46 percent in vehicle subjects (both P is less than 0.001, 2-sided). Week 2 efficacy response rates in NAFT-2% subjects were all lower than at week 4 but were significantly higher than week 2 vehicle-treated counterparts (P<0.025). Treatment-related AE occurred in 11 subjects (7 NAFT-2%, 4 vehicle) during the study. The most common AE in both groups were contact dermatitis (2 NAFT-2%), pruritus (2 vehicle), and application site reaction (1 per group). CONCLUSION: NAFT-2% applied once daily for two weeks (one-half the treatment duration for naftifine 1% cream) is efficacious and safe for the treatment of T. cruris.