7 comparative study of 2% sertaconazole solution and cream formulation in patients with tinea...

Am J Clin Dermatol 2007; 8 (6): 371-378ORIGINAL RESEARCH ARTICLE 1175-0561/07/0006-0371/$44.95/0

© 2007 Adis Data Information BV. All rights reserved.

Comparative Study of 2% Sertaconazole Solutionand Cream Formulations in Patients with TineaCorporis, Tinea Pedis Interdigitalis, or aCorresponding CandidosisClaudia Borelli,1 Gunther Klovekorn,2 Thomas-Matthias Ernst,3 Rolf-Hasso Bodeker,4 Hans Christian Korting1

and Claudia Neumeister5

1 Department of Dermatology and Allergology, Ludwig-Maximilian-University, Munich, Germany2 Medical Practice for Skin and Venereal Diseases, Gilching, Germany3 Medical Practice for Skin and Venereal Diseases, Berlin, Germany4 Institute for Medical Informatics, Justus Liebig University, Gieβen, Germany5 Department of Medical Science/Clinical Research, Dr. R. Pfleger GmbH, Bamberg, Germany

Background: Based on the results of numerous preclinical and clinical studies, sertaconazole can be consideredAbstracta safe and effective drug for the treatment of fungal skin infections.Objective: The objective of the study was to compare the efficacy of a solution containing 2% sertaconazolewith the well established 2% sertaconazole cream formulation in patients with tinea corporis, tinea pedisinterdigitalis, or a corresponding candidosis.Methods: This was a prospective, open-label, randomized, controlled, parallel-group, multicenter, noninferiori-ty therapy study. Patients received either sertaconazole solution or cream twice daily for 28 days. The fullanalysis set comprised 160 patients in the solution group and 153 patients in the cream group. The primaryefficacy parameter was a combination of culture test result and total clinical score. Efficacy was defined byeradication of the pathogen and reduction of the total clinical score between pretreatment and the final visit.Results: Efficacy was documented in 90.6% of patients using the solution and 88.9% of those using the cream(full analysis set). No adverse events occurred.Conclusion: Solution and cream formulations of 2% sertaconazole applied for 28 days were associated withcomparable efficacy and safety in the treatment of fungal skin infections.

Background Sertaconazole, an imidazole derivative, is used for the topical

treatment of mycoses of the skin. This agent has demonstratedMycoses of the human skin caused by dermatophytes or yeasts

high in vitro[1-14] and in vivo[15-19] antifungal activity against aare common and widespread diseases. The therapeutic armamen-

broad range of pathogenic yeasts and dermatophytes, together withtarium for the treatment of mycotic infections of the skin compris-antibacterial activity against Gram-positive bacteria.[20] In severales various different options, both with respect to the antifungalin vitro studies sertaconazole has also been found to be equallyagent and its vehicle. With any given antifungal, use of variousactive to, and frequently more active than, other azole antifun-formulations may be necessary to achieve optimal treatment de-gals.[9,10] The fungistatic and fungicidal activities of sertaconazolepending on the skin type, localization, size and characteristics of

the lesion, and the special needs of a given patient. result from indirect effects on fungal cell membrane synthesis

372 Borelli et al.

Table I. Distribution of gender, median, and corresponding 95% CIs of age (y), height (cm), and weight (kg) in patients with tinea or candidosis treated with2% sertaconazole solution or cream (full analysis set)

Demographic variable Solution (n = 160) Cream (n = 153)

Sex (%)

men 109 (68.13) 107 (69.93)

women 51 (31.88) 46 (30.07)

Age (y) [median (95% CI)] 44.5 (42.0, 52.0) 48.0 (43.0, 54.0)

Height (cm) [median (95% CI)] 174.0 (172.0, 175.0) 175.0 (173.0, 178.0)

Weight (kg) [median (95% CI)] 77.0 (75.0, 80.0) 79.0 (76.0, 83.0)

(inhibition of ergosterol biosynthesis) and direct effects on fungal study protocol was approved by the relevant Ethics Committeesmembrane permeability/integrity.[6,7,21-23] before the start of the study. According to the study protocol, 480

patients (240 patients in each therapy group) had to be recruited inVarious clinical trials using a cream formulation of sertacon-total to obtain the required ≈160 patients in each therapy groupazole have shown excellent efficacy and safety for this agent in thewith a confirmed fungal infection. Twenty-four centers in Ger-treatment of different types of superficial mycosis.[15,18,19] Formany, all dermatologic practices, participated in the study.example, a double-blind, randomized, controlled, parallel-group,

multicenter study of 631 patients found that patients treated with After providing informed consent, eligible men and women2% sertaconazole cream were cured earlier and more likely to be aged 18–70 years with presumed tinea corporis or tinea pediscured than those treated with miconazole cream.[15] The most interdigitalis as a result of dermatophytes, or a candidosis as acommon adverse event following use of sertaconazole cream was result of Candida species on corresponding parts of the body, werelocalized erythema. No systemic adverse events or changes in randomly assigned to one of the two therapy groups. One grouplaboratory parameters were observed in the two treatment groups. received 2% sertaconazole solution provided in a pump spray and

In 1992, Agut et al.[24] demonstrated equivalent pharmacokine- the other 2% sertaconazole cream formulation (Mykosert® 1

tic behavior for cream and solution formulations of 2% sertacon- Creme, Dr. R. Pfleger GmbH, Germany under license of Ferrerazole. However, when this study was commenced, only the cream International, Barcelona, Spain). Study medication had to be ap-formulation of sertaconazole was available in Germany. Develop- plied twice daily for 28 days according to the treatment durationment of a solution formulation of sertaconazole is desirable be- specified in the summary of product characteristics for the cream.cause the availability of a solution would widen the range of There were three visits for each patient: a pretreatment visittreatment options, for example, for the treatment of large lesions or (visit 1), an intermediate visit (visit 2) after 2 weeks, and the finalin the context of application to sites that are difficult to access visit (visit 3) after 2 further weeks of treatment. At each visit abecause of limited patient mobility. specimen was obtained for culture and a clinical assessment of

The rationale of the study was to compare the efficacy and signs/symptoms was completed by the investigator. All culturetolerability of a solution containing 2% sertaconazole with those tests were performed by a central laboratory (Labor L+S AG,of the well established 2% sertaconazole cream formulation (non- D-97708 Bad Bocklet). The test conditions were two agar platesinferiority hypothesis) in the hope of identifying an alternative per sample (Sabouraud-Glucose-Agar with and without ciclohex-formulation for the treatment of the most common fungal skin imide), aerobic, 30°C ± 1°C for 28 days, and daily readings.diseases. Identification of the pathogens was carried out up to the family/

genus level (dermatophytes or Candida species).Material and Methods

The main inclusion criterion was a positive culture test at theThis clinical trial was conducted conforming to European Com- pretreatment visit. As the result of the culture test was not avail-

munity Good Clinical Practice (EC-GCP) standards as a prospec- able until 3–4 weeks after the pretreatment visit, patients weretive, open-label, randomized, controlled, parallel-group, multicen- included on the basis of clinical signs and symptoms indicative ofter noninferiority therapy study in accordance with the Revised the various target diseases with a severity reflected by a totalDeclaration of Helsinki, local laws, and regulations. The final clinical score (TCS) of ≥6, and a positive finding on direct

1 The use of trade names is for product identification purposes only and does not imply endorsement.

© 2007 Adis Data Information BV. All rights reserved. Am J Clin Dermatol 2007; 8 (6)

Solution vs Cream Formulations of 2% Sertaconazole 373

Table II. Distribution of the localization of the mycosis classified into three categories in patients with tinea or candidosis treated with 2% sertaconazolesolution or cream (full analysis set)

Therapy Localization of mycosis Total (n)

foot trunk, groin combinations thereof

n % n % n %

Solution 125 78.13 32 20.00 3 1.88 160

Cream 108 70.59 42 27.45 3 1.96 153

All patients 233 74.44 74 23.64 6 1.92 313

microscopic examination. The TCS was determined by assessment each group was required. Therefore, the following assumptionsof the following five signs and symptoms by the investigator: were made: the expected difference in proportions was 0.00, theerythema, desquamation, vesicles, pustules, and itch (the latter success rate in the group treated with cream (πcream) was 0.65, andwas determined by investigator questioning). All signs and symp- the noninferiority range was –0.15 to ∞. Because the result of thetoms were assessed using an intensity scale that was defined as: first culture test was not known until the intermediate examination,0 = absent, 1 = mild, 2 = moderate, and 3 = severe. The TCS was the assumption was made that ≈40% would meet the secondarycalculated by adding up the scores for each sign and symptom. exclusion criterion “lack of verification of dermatophytes and/or

Candida species by a positive culture test at the time of inclusion.”Patients with systemic mycosis or mycosis of the hands, face,or scalp were excluded from the study. Patients experiencing The secondary parameters were the result of the culture test andoropharyngeal mycosis and/or vaginal mycosis were excluded the TCS (including the clinical signs and symptoms: erythema,from the study if fungal skin infection was located on an adjacent desquamation, vesicles, pustules, and itching), which were ana-skin area. Pretreatment with antifungal drugs and immunosuppres- lyzed separately. Adverse events were documented at the inter-sive agents within 14 and 30 days, respectively, prior to study start mediate and final examinations.was not allowed. Further exclusion criteria were pregnancy, lacta-tion, or inadequate contraception in women of child-bearing po-

Statistical Analysestential; severe psychiatric illnesses; known allergies to sertacon-azole or vehicle ingredients; and participation in another studywithin 30 days prior to study commencement. Data management and analyses were performed using Access

2000 (Microsoft, Redwood, WA,USA), SAS V8 (SAS Institute,The dichotomous primary efficacy parameter was based on aCary, NC, USA), TESTIMATE 6.0 (idv, Gauting, Germany), andcombination of culture test and clinical assessment (TCS). SuccessStatXact 5.0 (Cytel, Cambridge, MA, USA). The analysis of thewas defined as eradication of the pathogen at the final visit andprimary parameter was performed in the confirmatory sense usingreduction of the TCS by at least two points between pretreatmentthe exact Rohmel-Mansmann-Test. The secondary parametersand the final visit. In order to be able to reject the null hypothesiswere analyzed exploratively. In order to check for possible centerthat the success rate associated with treatment with solution waseffects, the secondary parameter ‘result of culture test’ was ana-inferior to the success rate associated with treatment with cream inlyzed in nonstratified and stratified manners.favor of the alternative hypothesis, inclusion of 160 patients in

Table III. Distribution of pathogens detected by culture test at the pretreatment visit in patients with tinea or candidosis treated with 2% sertaconazolesolution or cream (full analysis set)

Therapy Pathogens detected by culture test at pretreatment visit Total (n)

Candida spp. dermatophytes Candida spp. and dermatophytes

n % n % n %

Solution 8 5.00 147 91.88 5 3.13 160

Cream 12 7.84 138 90.20 3 1.96 153

All patients 20 6.39 285 91.05 8 2.56 313


374 Borelli et al.

Table IV. Frequency of success on the primary endpoint with corresponding 95% CIs in patients with tinea or candidosis treated with 2% sertaconazolesolution or cream (full analysis set)

Therapy Success on primary endpoint

no yes 95% CI total (n)

n % n %

Solution 15 9.38 145 90.63 85.01, 94.66 160

Cream 17 11.11 136 88.89 82.81, 93.39 153

All patients 32 10.22 281 89.78 85.87, 92.90 313

Results gory ‘foot’ (in particular interdigital spaces), which was docu-mented in 78.1% of patients in the solution group and 70.6% ofpatients in the cream group (table II).

Analysis Sets and Baseline Demographics

A total of 535 patients were recruited and randomized. All Distribution of Pathogens

patients received at least two boxes of study medication, whichThe culture test detected the pathogens ‘Candida,’ ‘dermato-meant that the sample size of the safety population (nSafety ) was

phytes,’ and a combination of both. The results of the culture tests535. As the result of the first culture test was not known until visitat pretreatment examination indicated that the mycosis was most2 or visit 3, 39.6% of patients did not fulfil the main inclusionfrequently caused by dermatophytes alone (91.1% of all patients).criterion of ‘positive culture test at pretreatment visit’ and there-Candida alone was found in only 6.4% of all patients. The distri-fore were not included in the full analysis set (FAS). Taking intobution of pathogens detected by culture test at the pretreatmentaccount the intention-to-treat principle on the one hand and thevisit in the FAS subdivided by therapy group is shown in table III.International Conference on Harmonization E9 guideline (“cir-

cumstances that might lead to excluding randomized subjects fromPrimary Efficacy Parameter

the full analysis set”)[25] on the other, 313 patients (nFAS) wereAnalysis of the primary efficacy parameter in the FAS showed

included in the FAS, consisting of 160 treated with solutionthat success was achieved in 145 of 160 patients (90.6%) in the

(nsolution) and 153 treated with cream (ncream). Excluding patientssolution group, and 136 of 153 patients (88.9%) in the cream

with relevant protocol violations (n = 68) or premature studygroup (table IV). The observed success rates were comparable in

termination (n = 11), the per-protocol set (PP) encompassed 234both treatment groups (difference between success rates: solution

patients (nPP), of which nsolution = 124 and ncream = 110. Theminus cream ∆p = 0.017). Similar results were obtained when

demographic data of patients in the FAS are shown in table I.analysing the PP set. Success when using the solution could beobserved in 114 of 124 patients (91.9%), and when using cream inLocalization of Mycosis100 of 110 patients (90.9%) with ∆p = 0.010. The one-sided 97.5%

The localization of the mycosis was recorded at the pretreat- CI was a subset of the noninferiority region in both analyses.ment visit. For analysis, the localizations were combined into three Sertaconazole solution was proven to be equally efficacious tocategories. The main localization of the mycosis was in the cate- sertaconazole cream in both analysis sets.

Table V. Frequency of a negative culture test result at visit 3 with corresponding 95% CIs in patients with tinea or candidosis treated with 2% sertaconazolesolution or cream (full analysis set)a

Therapy Result of culture test at final examination

negative positive total (n)

n % 95% CI n %

Solution 145 90.63 85.01, 94.66 15 9.38 160

Cream 137 89.54 83.57, 93.90 16 10.46 153

All patients 282 90.10 86.24, 93.17 31 9.90 313

a Under the hypothesis that the probability of success was the same in both therapy groups, the computed p-value in the stratified analysis waspCochran-Mantel-Haenszel = 0.631. The p-value for the non-stratified analysis was pFisher’s exact = 0.850.



group, and from 95.4% to 9.9% in the cream group. The propor-tion of patients with ‘moderate’ or ‘severe’ itch was reduced from81.9% at the pretreatment visit to 1.3% at the final visit in thesolution group, and from 84.3% to 3.3% in the cream group.Vesicles and pustules were comparatively less frequent at thepretreatment visit (‘moderate’ or ‘severe’ frequencies were ≈23%and 10%, respectively) and data for these signs/symptoms aretherefore not shown.

Safety

At the intermediate and final visits, patients were asked if any

33 23

99 94

22 11

100 102

52 47

108108

21 2430 33

0

40

80

120

160

Solution Cream Solution Cream Solution Cream

Visit 1 Visit 2 Visit 3

Pat

ient

s

SevereModerateMildAbsent

Fig. 1. Severity of erythema at the pretreatment (visit 1), intermediate(visit 2), and final visit (visit 3) in patients with tinea or candidosis treatedwith 2% sertaconazole solution or cream (full analysis set). Exact patientnumbers <10 are not shown in the figure.

adverse event had occurred since the previous visit. No patientsSecondary Efficacy Parameters reported a serious adverse event. 16 (6.1%) of patients applying

the solution and 20 (7.4%) of those applying cream reported atEach component of the primary parameter (result of the cultureleast one adverse event occurring during the study (table VI). Oftest at the final visit and the difference in the TCS betweenthe 18 adverse events reported by 16 patients in the solution group,pretreatment and the final visit) was analyzed separately.only three events (eczema in two patients, itch in one patient) were

In the FAS, 145 patients (90.6%) in the solution group, and 137 considered to be possibly related to use of sertaconazole solution.patients (89.5%) in the cream group showed a negative culture test Of the 21 adverse events reported by 20 patients in the creamresult at the final visit (table V). Monitoring for possible center group, again only three events (itch in two patients, mild burningeffects revealed no evidence of a difference between the cream and in one patient) were considered to be possibly related to use ofthe solution group by either nonstratified (pFisher’s exact = 0.850) or sertaconazole cream. Thus, in both treatment groups, adversestratified (pCochrane-Mantel-Haenszel = 0.631) analysis, i.e. there is no events that were considered possibly related to study medicationcenter effect. occurred in only 1.1% of patients.

The maximum change in TCS was an improvement of 13 pointsin both treatment groups between pretreatment and the final visit. SummaryThe median change in the TCS between pretreatment and the final The confirmatory analysis showed evidence of a noninferiorvisit was an improvement of six points in the solution group antifungal effect of sertaconazole solution versus the well estab-compared with seven points in the cream group. lished reference drug sertaconazole cream. Thus, sertaconazole

In the PP set, 114 patients (91.9%) in the solution group and solution was proven to be at least therapeutically equivalent to the101 patients (91.8%) in the cream group showed a negative culture cream. The incidence of active investigational medicinal product-test result at the final visit. The median change in TCS was an related adverse events was low and no serious adverse events wereimprovement of six points in the solution group and six and one- reported.half points in the cream group.

For these two secondary parameters, there was no evidence ofany difference between the cream and the solution concerningeither the occurrence of a negative culture test result or in changeof TCS.

Changes in erythema, desquamation and itch during the studyin the FAS are shown in figures 1, 2, and 3, respectively. Theproportion of patients with ‘moderate’ or ‘severe’ erythema wasreduced from 86.3% at the pretreatment visit to 2.6% at the finalvisit in the solution group, and from 92.2% to 6.6% in the creamgroup. The proportion of patients with ‘moderate’ or ‘severe’desquamation was reduced from 96.3% to 16.8% in the solution

0

40

80

120

160



Pat

ient

s

51 6795

10178

69

85 90

41 27 2569 56

17

1215


Fig. 2. Severity of desquamation at the pretreatment (visit 1), intermediate(visit 2), and final visit (visit 3) in patients with tinea or candidosis treatedwith 2% sertaconazole solution or cream (full analysis set). Exact patientnumbers <10 are not shown in the figure.


376 Borelli et al.

‘acuity and type of the disease,’ ‘skin type, skin status,’ ‘localiza-tion of the disease,’ ‘environmental factors’, and ‘cosmetic consid-erations.’

Considering this information as a whole, current recommenda-tions on selection of dermatologic vehicles should not only becalled ‘eminence-based,’ but also ‘evidence-based’ – at least up toa point. However, the best evidence available in this contextappears to be only partially illuminating. Nevertheless, even inrecent times, pharmaceutical companies have tended to meetclinicians’ expectations in terms of providing a variety of formula-tions when a new topical antifungal agent is introduced. This is

0

40

80

120

160



Pat

ient

s

74 61

131 132

20 19

66 77

22 14

73 72

18 1158 57


Fig. 3. Severity of itching at the pretreatment (visit 1), intermediate (visit 2),and final visit (visit 3) in patients with tinea or candidosis treated with 2%sertaconazole solution or cream (full analysis set). Exact patient numbers<10 are not shown in the figure.

particularly the case with the frequently used allylamine terbina-fine.[29] Indeed, a variety of terbinafine formulations incorporating

Discussioncream and solution were evaluated in the systematic review byKorting et al.[29] However, while the superiority of various formu-The current German guideline on tinea of glabrous skinlations including the active pharmaceutical ingredient over vehi-(Arbeitsgemeinschaft der Wissenschaftlichen Medizinischencles has been demonstrated, no comparative trials have beenFachgesellschaften-Leitlinie Nr. 013/002) states, in agreementpublished that provide an indication of the relative efficacy andwith other guidelines,[26] that this type of fungal disease should, assafety of the terbinafine formulations. The comparatively newa rule, be treated topically using representatives of accepted clas-agent sertaconazole has also been formulated in different versions,ses of active pharmaceutical ingredients. Azoles are named as theincluding gel, cream, powder, and solution.[20] However, a recentfirst class of drugs of choice followed by hydroxypyridones,review also did not provide any information on the relative effi-allylamines, and morpholines. Sertaconazole is one of six individ-cacy and safety of the various formulations.[20]ual topical azoles specifically referred to in the German guidelines.

The aim of the present trial was to address the relative efficacyThe guideline also states that the appropriate formulation shouldand safety of two frequently used formulations of a topical anti-be selected for treatment of any individual case. In addition, thefungal, i.e. cream and solution. As with other topical antifungalguideline states that, depending on the localization and type ofagents, sertaconazole cream was introduced first and has thusmanifestation of the infection, several different formulationsattained the role of standard therapy. The data obtained within themight be of use. The formulation types named, in order, are cream,trial were obtained in a clinical study that addressed the subject ofsolution, (liposome) gel, paste, and powder. The statement, how-noninferiority in a confirmatory manner.ever, was based on the opinion of a panel of experts, as reflected

by its classification as a so-called level 1 guideline. On the subject Use of ‘rigorous methods’ is clearly important when con-of the relative relevance of various topical formulations for use in ducting clinical trials to assess equivalence.[30] No placebo groupskin disease, it is peculiar that even recent comprehensive reviews was included in this study for two reasons. First, the superiority ofof various aspects of ‘dermatologic vehicles’ have stated that sertaconazole[31] and of azole antifungals in general comparedselection of the type of vehicle should be based on a ‘a few simple with placebo has already been proven.[29] Second, there was nofactors’, as described by the authors of leading German textbooks reason to believe before the trial that one of the formulation typespublished as early as 1982.[27,28] The factors named comprise would be proven to be definitely superior and it was not the aim of

Table VI. Frequency of adverse events during the study in patients with tinea or candidosis treated with 2% sertaconazole solution or cream (safety set)

Therapy Any adverse event during study Total (n)

not knowna no yes

n % n % n %

Solution 11 4.18 236 89.73 16 6.08 263

Cream 4 1.47 248 91.18 20 7.35 272

All patients 15 2.80 484 90.47 36 6.73 535

a Information regarding the possible occurrence of an adverse event is missing.



The authors would like to thank Anna Wolf for proofreading and Christinethe study to show superiority against placebo but rather equalScheibelhut for valuable assistance in data management and data analysis.efficacy of two different formulations of the same active sub-

stance. It is important to note that a certain degree of spontaneousReferencesrecovery (e.g. in one study, the cure rate was 24% in the placebo

1. Carrillo-Munoz AJ, Torres-Rodriguez JM. In-vitro antifungal activity of sertacon-group compared with 60% in the miconazole group[32]) was notazole, econazole, and bifonazole against Candida spp. J Antimicrob Chemother

taken into account in this study. Nevertheless, the high cure rates 1995; 36: 713-62. Carillo-Munoz AJ, Tur-Tur C. Comparative study of antifungal activity of serta-in this study suggest an excellent efficacy for sertaconazole, and

conazole, terbinafine, and bifonazole against clinical isolates of Candida spp.,we believe that this type of evaluation has become widely accept- Cryptococcus neoformans and dermatophytes. Chemotherapy 1997; 43: 387-92

3. Carrillo-Munoz AJ, Tur-Tur C, Bornay-Llinares FJ, et al. Comparative study of theed, as evidenced by the increasing number of clinical trials com-in vitro antifungal activity of bifonazole, naftifine and sertaconazole againstparing a particular drug to an active control.[33]yeasts. J Chemother 1999; 11: 187-90

Proving the noninferiority of sertaconazole solution compared 4. Drouhet E, Dupont B. In vitro antifungal activity of sertaconazole. Arzneimittelfor-schung 1992; 42: 705-10with sertaconazole cream in a clinical context primarily means that

5. Martin-Mazuelos E, Aller AI, Morilla D, et al. Antifungal activity of sertaconazoledoctors treating patients with tinea of glabrous skin can feel free to in vitro against clinical isolates of Candida spp. Chemotherapy 1996; 42: 112-7

6. Palacin C, Sacristan A, Ortiz JA. In vitro activity of sertaconazole. Arzneimittelfor-select the type of formulation to be used according to currentschung 1992; 42: 699-705recommendations. However, the design of this trial means that it

7. Palacin C, Sacristan A, Ortiz JA. In vitro comparative study of the fungistatic andcannot answer the question of whether subgroups of patients with fungicidal activity of sertaconazole and other antifungals against Candida

albicans. Arzneimittelforschung 1992; 42: 711-4tinea of glabrous skin might benefit more from a topical antifungal8. Pfaller MA, Sutton DA. Review of in vitro activity of sertaconazole nitrate in the

cream or a solution, and in particular sertaconazole cream or treatment of superficial fungal infections. Diagn Microbiol Infect Dis 2006; 56:147-52solution. Answers to such questions can only be obtained from

9. Carrillo-Munoz AJ, Tur C, Estivill D, et al. In vitro antifungal activity of sertacon-specialized trials. In the context of sertaconazole solution it mightazole and bifonazole against dermatophytes. J Mycol Med 1995; 5: 235-8

be particularly rewarding to perform another trial comparing the 10. Carrillo-Munoz AJ, Tur C, Torres J. In vitro antifungal activity of sertaconazole,bifonazole, ketoconazole and miconazole against yeasts of the Candida genus.solution with the cream in patients with a particularly exudativeJ Antimicrob Chemother 1996; 37: 815-9

type of tinea, for example, in the toe-webs. 11. Carrillo-Munoz AJ, Brio S, Quindos G, et al. Sertaconazole: in vitro antifungalactivity against vaginal and other superficial yeast isolates. J Chemother 2001;13: 555-62Conclusion

12. Carrillo-Munoz AJ, Fernandez-Torres B, Cardenes DC, et al. In vitro activity ofsertaconazole against dermatophyte isolates with reduced fluconazole suscepti-The results of this study show that sertaconazole solution is atbility. Chemotherapy 2003; 49: 248-51

least therapeutically equivalent to the cream formulation. Serta- 13. Carrillo-Munoz AJ, Fernandez-Torres B, Guarro J. In vitro antifungal activity ofsertaconazole against 309 dermatophyte clinical isolates. J Chemother 2003;conazole solution is a new and safe therapeutic option for the15: 555-7

treatment of tinea corporis, tinea interdigitalis pedis, and cutane-14. Carrillo-Munoz AJ, Guglietta J, et al. In vitro antifungal activity of sertaconazole

ous candidosis. compared with nine other drugs against 250 clinical isolates of dermatophytesand Scopulariopsis brevicaulis. Chemotherapy 2004; 50: 308-13

15. Alomar C, Bassas S, Casas M, et al. Multi-centre double-blind trial on the efficacyAcknowledgmentsand safety of sertaconazole 2% cream in comparison with miconazole 2%cream on patients suffering from cutaneous mycoses. ArzneimittelforschungThe trial was funded by Dr. R. Pfleger GmbH, Bamberg, Germany and1992; 42: 767-73

Ferrer International, Barcelona, Spain. 16. Palacin C, Sacristan A, Ortiz JA. In vivo activity of sertaconazole in experimentalDr Neumeister is an employee of Dr. R. Pfleger GmbH, Bamberg, Ger- candidiasis in the mouse. Drugs Exp Clin Res 1990; 16: 469-73

many. Some of the authors and study group members received compensation 17. Palacin C, Sacristan A, Ortiz JA. In vivo activity of sertaconazole in experimentaldermatophytosis in guinea pigs. Arzneimittelforschung 1992; 42: 714-8for their contribution to the trial.

18. Pedragosa R, Gonzalez B, Martin M, et al. Therapeutic efficacy and safety of theThe authors are grateful to the additional members of the P183-Sertacona-new antimycotic sertaconazole in the treatment of cutaneous dermatophytosis.

zole Study Group encompassing Dr S. Baeblich (Berlin), Dr N. FischerArzneimittelforschung 1992; 42: 760-3

(Munchen), Dr H. Gorlich (Berlin), Dr R. Gollhausen (Dachau), 19. Umbert P, Nasarre J, Bello A, et al. Phase II study of the therapeutic efficacy andDr K. Winkelspecht/Dr D. Hiller (Bamberg), Dr K.G. Meyer (Berlin), safety of the new antimycotic sertaconazole in the treatment of superficial

mycoses caused by Candida albicans. Arzneimittelforschung 1992; 42: 757-60Dr M. Miehe (Berlin), Dr P. Schnabel (Munchen), Dr K. Stojanow (Berlin),20. Carrillo-Munoz AJ, Giusiano G, Ezkurra PA, et al. Sertaconazole: updated reviewDr V. von Liebe (Munchen), Dr G. von Hake (Frankfurt), Dr D. Greiner

of a topical antifungal agent. Expert Rev Anti Infect Ther 2005; 3: 333-42(Oberursel), Dr U. Wichmann-Henricks (Grunberg), Dr W. Brinkmann21. Agut J, Palacin C, Sacristan A, et al. Inhibition of ergosterol synthesis by sertacon-

(Herborn), Dr E. Klaubert (Offenbach), Dr S. Heilmann (Marburg),azole in Candida albicans. Arzneimittelforschung 1992; 42: 718-20

Dr E. Thomas (Marburg), Dr M. Groβ (Bamberg), Dr B. Wunscher (Amberg), 22. Agut J, Palacin C, Salgado J, et al. Direct membrane-damaging effect of sertacon-Dr D. Konietzko (Bamberg), Dr G. Falker (Frankenberg), and Dr R. Bartelt azole on Candida albicans as a mechanism of its fungicidal activity. Arzneimit-

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7 comparative study of 2% sertaconazole solution and cream formulation in patients with tinea...

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