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Bhushan Hardas - One of the best experts on this subject based on the ideXlab platform.
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detection and relevance of Naftifine hydrochloride in the stratum corneum up to four weeks following the last application of Naftifine cream and gel 2
Journal of Drugs in Dermatology, 2013Co-Authors: Stefan Plaum, Amit Verma, Alan B Fleischer, Babajide Olayinka, Bhushan HardasAbstract: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.
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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
Journal of Drugs in Dermatology, 2013Co-Authors: Linda Stein Gold, Leon H Kircik, Stefan Plaum, Amit Verma, Alan B Fleischer, Babajide Olayinka, Lawrence Charles Parish, Tracey C Vlahovic, Bhushan HardasAbstract: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)
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an open label pilot study of Naftifine 1 gel in the treatment of seborrheic dermatitis of the scalp
Journal of Drugs in Dermatology, 2012Co-Authors: Michael H Gold, Stefan Plaum, Alan B Fleischer, Tancy M Bridges, Edward V Avakian, Bhushan HardasAbstract: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.
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a randomized double blind vehicle controlled efficacy and safety study of Naftifine 2 cream in the treatment of tinea pedis
Journal of Drugs in Dermatology, 2011Co-Authors: Lawrence Charles Parish, Stefan Plaum, Alan B Fleischer, Edward V Avakian, Jennifer L Parish, Hirak Behari Routh, Bhushan HardasAbstract: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.
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a double blind randomized vehicle controlled study evaluating the efficacy and safety of Naftifine 2 cream in tinea cruris
Journal of Drugs in Dermatology, 2011Co-Authors: Lawrence Charles Parish, Stefan Plaum, Alan B Fleischer, Babajide Olayinka, Edward V Avakian, Eric J Pappert, Jennifer L Parish, Hirak Behari Routh, Bhushan HardasAbstract: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.
Stefan Plaum - One of the best experts on this subject based on the ideXlab platform.
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in vitro antifungal activity of Naftifine hydrochloride against dermatophytes
Antimicrobial Agents and Chemotherapy, 2013Co-Authors: Mahmoud A Ghannoum, N Isham, A Verma, Stefan Plaum, A Fleischer, B HardasAbstract:The incidence of superficial dermatophytoses is high in developed countries, and there remains a need for effective topical antifungals. In this study, we evaluated the in vitro antifungal activity of Naftifine hydrochloride, the active ingredient in Naftifine hydrochloride cream and gel 1% and 2%, against dermatophytes. The MICs and minimum fungicidal concentrations (MFCs) of Naftifine hydrochloride against 350 clinical strains, including Trichophyton rubrum, T. mentagrophytes, T. tonsurans, Epidermophyton floccosum, and Microsporum canis, were determined using the CLSI methodology. Subsets from this test panel were subsequently tested in a time-kill assay at 0.125×, 0.25×, 0.5×, and 1× the MFC for each isolate. CFU counts were performed over a period of 48 h of incubation. Additionally, in order to determine the potential for resistance development, six strains were subjected to 15 serial passages in concentrations higher than the MIC for each strain. MICs were determined following each passage. The MIC range against the dermatophyte isolates tested was 0.015 to 1.0 μg/ml, with Naftifine hydrochloride being fungicidal against 85% of the Trichophyton species. The time-kill assay showed dose-dependent activity, with the greatest reduction in the numbers of CFU corresponding to the highest drug concentration. There was no increase in MIC for any strains following repeated exposure to Naftifine hydrochloride. Naftifine hydrochloride demonstrated potent activity against all dermatophytes tested, and none of the isolates within this test panel demonstrated the potential for the development of resistance. Thus, future clinical studies of Naftifine hydrochloride against dermatophytes may be warranted for the treatment of superficial dermatophytoses.
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detection and relevance of Naftifine hydrochloride in the stratum corneum up to four weeks following the last application of Naftifine cream and gel 2
Journal of Drugs in Dermatology, 2013Co-Authors: Stefan Plaum, Amit Verma, Alan B Fleischer, Babajide Olayinka, Bhushan HardasAbstract: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.
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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
Journal of Drugs in Dermatology, 2013Co-Authors: Linda Stein Gold, Leon H Kircik, Stefan Plaum, Amit Verma, Alan B Fleischer, Babajide Olayinka, Lawrence Charles Parish, Tracey C Vlahovic, Bhushan HardasAbstract: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)
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an open label pilot study of Naftifine 1 gel in the treatment of seborrheic dermatitis of the scalp
Journal of Drugs in Dermatology, 2012Co-Authors: Michael H Gold, Stefan Plaum, Alan B Fleischer, Tancy M Bridges, Edward V Avakian, Bhushan HardasAbstract: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.
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a randomized double blind vehicle controlled efficacy and safety study of Naftifine 2 cream in the treatment of tinea pedis
Journal of Drugs in Dermatology, 2011Co-Authors: Lawrence Charles Parish, Stefan Plaum, Alan B Fleischer, Edward V Avakian, Jennifer L Parish, Hirak Behari Routh, Bhushan HardasAbstract: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.
Alan B Fleischer - One of the best experts on this subject based on the ideXlab platform.
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Naftifine hydrochloride gel 2 an effective topical treatment for moccasin type tinea pedis
Journal of Drugs in Dermatology, 2015Co-Authors: Linda Stein Gold, Amit Verma, Babajide Olayinka, Tracey C Vlahovic, Alan B FleischerAbstract:BACKGROUND Naftifine hydrochloride (Naftifine) is a topical antifungal of the allylamine class, displaying fungicidal and fungistatic activity. Naftifine is generally used to treat interdigital tinea pedis; however, systemic therapy is often prescribed by healthcare providers for moccasin tinea pedis. Well-controlled clinical data on topical antifungal therapy for moccasin tinea pedis is limited. OBJECTIVE The objective of this analysis is to present data from two pooled randomized, vehicle-controlled studies that evaluated efficacy of once daily topical Naftifine gel 2% and vehicle at end of treatment (week 2) and at 4 weeks post-treatment in subjects with moccasin tinea pedis. METHODS At visit 1, subjects were randomized to Naftifine gel 2% or vehicle groups and subjects underwent baseline mycology culture, KOH, and symptom (erythema, scaling, and pruritus) severity grading. Naftifine gel 2% and vehicle treatment were applied once daily for 2 weeks and the subjects returned at weeks 2 and 6 for efficacy evaluation (mycology culture and grading of symptom severity). A total of 1174 subjects were enrolled with interdigital tinea pedis with or without moccasin infection. Of these subjects, 674 subjects had interdigital presentation while 500 subjects had moccasin infection in addition to the interdigital presentation. All 1174 subjects with interdigital presentation satisfied the inclusion criteria of a minimum of moderate erythema and scaling, and mild pruritus. Of the 500 subjects who had moccasin presentation, 380 satisfied the same inclusion criteria as mentioned above. Since data was analyzed as observed cases, between 337 and 349 subjects had data available for analysis of efficacy. Mycologic cure is defined as a negative dermatophyte culture and KOH, treatment effectiveness is defined as mycologic cure and symptom severity scores of 0 or 1, and complete cure is defined as mycologic cure and symptoms severity scores of 0. RESULTS At week 6, the cure rates in the Naftifine arm vs. the vehicle were statistically higher (P < 0.0001) for mycological cure rate (65.8% vs. 7.8%), treatment effectiveness (51.4% vs 4.4%), and complete cure rate (19.2% vs 0.9%). CONCLUSION Two weeks application of topical Naftifine gel 2% is an effective monotherapy treatment for moccasin tinea pedis.
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an open label multi center multiple application pharmacokinetic study of Naftifine hcl gel 2 in pediatric subjects with tinea pedis
Journal of Drugs in Dermatology, 2015Co-Authors: Amit Verma, Babajide Olayinka, Alan B FleischerAbstract:BACKGROUND Tinea pedis is the most common superficial fungal infection. Naftifine hydrochloride is a topical antifungal of the allylamine class, displaying fungicidal activity and clinically significant anti-bacterial and anti-inflammatory effects. Clinical data on topical antifungal therapy using Naftifine for tinea pedis in a pediatric population is limited. OBJECTIVE To assess trends in efficacy, tolerability, safety, and to quantify the pharmacokinetics (PK) of topical Naftifine hydrochloride gel 2% in pediatric subjects with tinea pedis. METHODS Twenty-eight subjects (22 pediatric and 6 adult controls) were enrolled and treated in the study. Approximately 2 grams of Naftifine hydrochloride gel 2% was applied to each foot (4 grams total) for subjects with tinea pedis. Pharmacokinetic blood and urine samples were collected at various time points throughout the study. Efficacy was assessed based on potassium hydroxide, dermatophyte culture, and signs and symptom results at days 7, 14, and 28. Adverse event information was collected routinely. RESULTS The rate and extent of systemic exposure among the pediatric and adult control subjects was low. Adverse events were minimal and were not related to treatment. Positive results were observed as early as day 7; however the proportion of subjects achieving success generally increased over time through day 28 in both treatment groups. CONCLUSIONS Naftifine hydrochloride gel 2% was found to be well tolerated and safe. Trends in clinical benefit were observed throughout the treatment period; however, continued improvement in efficacy rates were observed during the post-treatment period.
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detection and relevance of Naftifine hydrochloride in the stratum corneum up to four weeks following the last application of Naftifine cream and gel 2
Journal of Drugs in Dermatology, 2013Co-Authors: Stefan Plaum, Amit Verma, Alan B Fleischer, Babajide Olayinka, Bhushan HardasAbstract: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.
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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
Journal of Drugs in Dermatology, 2013Co-Authors: Linda Stein Gold, Leon H Kircik, Stefan Plaum, Amit Verma, Alan B Fleischer, Babajide Olayinka, Lawrence Charles Parish, Tracey C Vlahovic, Bhushan HardasAbstract: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)
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an open label pilot study of Naftifine 1 gel in the treatment of seborrheic dermatitis of the scalp
Journal of Drugs in Dermatology, 2012Co-Authors: Michael H Gold, Stefan Plaum, Alan B Fleischer, Tancy M Bridges, Edward V Avakian, Bhushan HardasAbstract: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.
R Soloeta - One of the best experts on this subject based on the ideXlab platform.
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allergic contact dermatitis from Naftifine in a child without cross reaction to terbinafine
Journal of The European Academy of Dermatology and Venereology, 1998Co-Authors: J J Goday, Magdalena Gonzalezguemes, Ignacio Yanguas, R Ilardia, R SoloetaAbstract:Allergic contact dermatitis from Naftifine has been scarcely described in the English literature, all of them in adults. We report a case of a 12-year-old girl who developed an acute eczema on her neck after application of a Naftifine cream. This fact was confirmed by a patch-test study. We did not find a cross-reaction to terbinafine, a structurally linked allylamine.
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case reportallergic contact dermatitis from Naftifine in a child without cross reaction to terbinafine
Journal of The European Academy of Dermatology and Venereology, 1998Co-Authors: J J Goday, Magdalena Gonzalezguemes, Ignacio Yanguas, R Ilardia, R SoloetaAbstract:Allergic contanct dermatitis from Naftifine has been scarcely described in the English literature, all of them in adults. We report a case of a 12-year-old girl who developed an acute eczema on her neck after application of a Naftifine cream. This fact was confirmed by a patch test study. We did not find a cross-reaction to terbinafine, a structurally linked allylamine.
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design of two alternative routes for the synthesis of Naftifine and analogues as potential antifungal agents
Molecules, 2018Co-Authors: Rodrigo Abonia, Alexander Garay, Juan C Castillo, Braulio Insuasty, Jairo Quiroga, Manuel Nogueras, Justo Cobo, Estefania Butassi, Susana ZacchinoAbstract:Two practical and efficient approaches have been implemented as alternative procedures for the synthesis of Naftifine and novel diversely substituted analogues 16 and 20 in good to excellent yields, mediated by Mannich-type reactions as the key step of the processes. In these approaches, the γ-aminoalcohols 15 and 19 were obtained as the key intermediates and their subsequent dehydration catalyzed either by Bronsted acids like H2SO4 and HCl or Lewis acid like AlCl3, respectively, led to Naftifine, along with the target allylamines 16 and 20. The antifungal assay results showed that intermediates 18 (bearing both a β-aminoketo- and N-methyl functionalities in their structures) and products 20 were the most active. Particularly, structures 18b, 18c, and the allylamine 20c showed the lowest MIC values, in the 0.5–7.8 µg/mL range, against the dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes. Interesting enough, compound 18b bearing a 4-Br as the substituent of the phenyl ring, also displayed high activity against Candida albicans and Cryptococcus neoformans with MIC80 = 7.8 µg/mL, being fungicide rather than fungistatic with a relevant MFC value = 15.6 µg/mL against C. neoformans.
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Naftifine analogues as anti trypanosoma cruzi agents
ChemInform, 2010Co-Authors: Alejandra Gerpe, Lucia Boiani, Paola Hernandez, Maximiliano Sortino, Susana Zacchino, Mercedes Gonzalez, Hugo CerecettoAbstract:The Naftifine analogues are designed as potential T.cruzi membrane sterol biosynthesis inhibitors.
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Naftifine analogues as anti trypanosoma cruzi agents
European Journal of Medicinal Chemistry, 2010Co-Authors: Alejandra Gerpe, Lucia Boiani, Paola Hernandez, Maximiliano Sortino, Susana Zacchino, Mercedes Gonzalez, Hugo CerecettoAbstract:Chagas disease represents a relevant health problem in Central and South America. The first line of treatment is Nifurtimox and Benznidazole which have a great deal of disadvantages that demands the rapid generation of therapeutic alternatives. Based in our research on aza-thiaheterocycles as anti-Trypanosoma cruzi agents we identified pharmacophores that act through oxidative stress. Here, we describe the synthesis and the activity of new containing bioactive-heterocycles analogues of Naftifine as potential T. cruzi membrane sterol biosynthesis inhibitors. Benzimidazole 1,3-dioxides (11 and 13) and quinoxaline 1,4-dioxides (22 and 23) displayed excellent parasite/mammal selectivity indexes. Analysis of the free sterols from parasite incubated with the compounds showed that any of them are able to accumulate squalene suggesting that in the anti-T. cruzi mechanism of action is not involved the inhibition of sterol biosynthesis. Some derivatives were also tested as antifungal agents. The results obtained in the present work open potential therapeutic possibilities of new compounds for these infectious diseases.
