Original article

Comparative efficacy and tolerability of Ketomousse (ketoconazole

foam 1%) and ketoconazole cream 2% in the treatment of pityriasis
versicolor: results of a prospective, multicentre, randomised study

E. M. Di Fonzo,1 P. Martini,2 C. Mazzatenta,2 L. Lotti1 and S. Alvino3

1
Department of Dermatology, Florence University, Florence, Italy, 2Department of Dermatology, Campo di Marte Hospital, Lucca, Tuscany, Italy and 3R&D
Department, Mipharm S.p.A., Milan, Italy

Summary Ketomousse (K), a new thermophobic formulation (ketoconazole 1%), has proven its
efficacy in the treatment of dandruff, caused by the same agent as pityriasis versicolor
(PV). The objective of this study was to compare the efficacy and tolerability of K
thermophobic foam vs. ketoconazole cream 2% (N) in the treatment of PV. Forty-six
patients (22 in K and 24 in N group) with PV involving no more than 15% of the total
trunk surface were randomly assigned for treatment either with K or N once daily for
14 days. Three weeks after the completion of treatment, improvement rate and side-
effects were evaluated by clinical and mycological examination (WoodÕs light). Follow-
up was available for 81% of subjects. Complete resolution was observed in five patients
(29%) in K group and in nine (47%) in N group (P = 0.291). One patient in the N
group reported urticaria while no adverse events were reported for K. Both products
were cosmetically acceptable with respect to feasibility of application and formulation
with a preference for K. Ketomousse (1% ketoconazole) provides an equal efficacy and
tolerability compared to ketoconazole cream 2%. Therefore, Ketomousse could be
considered an excellent therapeutic option in the treatment of PV.

Key words: Ketoconazole 1%, ketoconazole 2%, pityriasis versicolor.

A number of topical treatment options have shown

Introduction
Pityriasis versicolor (PV) is a common superficial fungal
infection of the skin. Malassezia, a normal human
saprophyte, is considered to be its aetiological agent.
Under exogenous and endogenous conditions the fun-
gus changes from the blastospore form to the patho-
genic mycelial form. This occurs under the influence of
predisposing agents, like high temperature, high relative
humidity, greasy skin, hyperhidrosis, hereditary factors,
corticosteroids treatment and immunodeficiency.1–3
Malassezia causes scaly hypo- or hyperpigmented
lesions exclusively in the stratum corneum of the upper
trunk, scalp and face.
Correspondence: Simonetta Alvino, MD, R&D Department, Mipharm S.p.A.,
Via B. Quaranta 12, 20141 Milano, Italy.
Tel.: +39 2 5354 8007. Fax: +39 2 5354 8064.
E-mail: simonetta.alvino@mipharm.it
Accepted for publication 19 January 2008
to be effective. Currently, therapeutic interest is
focussed on synthetic Ô-azoleÕ antifungal drugs, which
interfere with the sterol metabolism of the infectious
agent.4–8
Ketomousse (Mipharm S.p.A., Milano, Italy), a
thermophobic foam formulation containing ketoconaz-
ole 1% zinc pyrithione and salicylic acid, demon-
strated a triple action in dermatologic conditions:
keratin-regulator, promoting removal of flakes from
the stratum corneum with consequent reduction of its
production; antimicrobic against the proliferation of
the fungus responsible for desquamation; grease
modulator regulating the production of sebaceous
glands.
The thermophobic foam is a new transcutaneous
delivery system: this technology uses a temperature-
activated mousse which, when applied to the skin,
rapidly melts and evaporates allowing a non-residue-
sustained penetration of the active compound. In
comparison with lotions, the mousse technology has

 2008 Mipharm S.p.A., Milan

doi:10.1111/j.1439-0507.2008.01508.x Journal compilation  2008 Blackwell Publishing Ltd • Mycoses 51, 532–535

a significantly shorter evaporation time. Experimental
studies have shown that the thermophobic mousse
allows a sixfold transcutaneous penetration of the
active compound in comparison to lotions. This
improved pharmacokinetics induces a significantly
higher clinical efficacy when compared with lotion
formulations.
Ketomousse is a white, soft foam. This compound
has proven to be significantly more effective than
ketoconazole 2% scalp fluid (a medicated antifungal
shampoo) in a randomised, single-blind study in the
treatment of moderate-to-severe dandruff, caused by the
same aetiological agent responsible for PV.9
In addition, in a pilot study of 15 patients affected by
PV, Ketomousse when applied once daily for 7 days
caused complete resolution in 60% of the patients while
for the others a second therapeutic cycle of 7 days had
to be repeated to obtain the same optimal result (A.
Bigardi, personal communication).
Therefore, the aim of the present study was to
evaluate whether Ketomousse is as effective and safe
as the standard treatment (ketoconazole 2% cream) in
patients affected by PV.
Patients and methods
The present study was prospective, multicentre, rando-
mised 1 : 1, parallel group over a 5-week period to
assess efficacy, tolerability and cosmetic acceptability of
Ketomousse, compared with ketoconazole 2% cream.
Patients were eligible for randomisation if aged
between 18 and 70, affected by PV confirmed by
microscopic and WoodÕs light examinations and involv-
ing no more than 15% of the total surface of trunk
(thorax and dorsum). Exclusion criteria were the
following: hypersensitivity to trial medications, preg-
nancy or breastfeeding, presence of other active cuta-
neous inflammatory or infective pathologies in the same
target area, utilisation of other topical or systemic drugs
which could interfere with patient or experimental drug
evaluation in the investigatorÕs opinion, treatment with
topical or systemic antifungal therapy in the previous
4 weeks prior to enrolment.
Treatment allocation was randomly assigned by a
computer generated randomisation list (Arcus Quick-
stat, Cambridge, UK) to one of the two treatment arms:
Ketomousse (Mipharm) or ketoconazole 2% cream
(Nizoral; Janssen-Cilag, Latina, Italy), single daily
application in the evening for 14 days. Every morning
the residual drug needed to be washed away. Clinical
evaluation was done at baseline, 1, 2, 5 weeks and
finally 3 months since the beginning of the treatment.
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Ketomousse in pityriasis versicolor
The clinical evaluation of the disease severity was
performed by a global assessment of clinical severity
(GACS score).
A patient was considered to have obtained complete
resolution if all visual evidence ⁄ symptoms of fungal
disease have disappeared by a global clinical score (GAS
score) = 0 and negative WoodÕs light and mycological
examination.
The GAS score ranged as follows: 0 = complete
resolution; 1 = resolution with residual hypo-pigmen-
tation and negative mycological examination; 2 = stea-
dy lesions (still scaling); 3 = worsening.
Patients were asked to report any adverse event and
cosmetically evaluate the study medications through a
questionnaire using a graded quantitative score.
Patients who interrupted the treatment for reasons
not related to study medications were considered as
drop-outs.
The protocol was approved by the Ethics Committee
of each participating centre and all patients gave their
written informed consent.
A statistical analysis between the two groups was
performed using Mann–Whitney non-parametric test
for continuous variables and v2 test for nominal
variables. All patients were evaluated for efficacy
analysis on an intention-to-treat basis. Statistical sig-
nificance was set at P < 0.05.
Analysis have been performed using the statistical
software STATA (StataCorp., 2006 Stata Statistical Soft-
ware: release 9.0, College station, TX, USA).
Results
Between October 2005 and February 2007, 46 consec-
utive patients were enrolled in two Italian sites, 22
assigned to K and 24 to N treatment.
Table 1 shows patients demographics and duration of
the PV disease in the two study groups. There were no
significant clinical differences at baseline between the
two groups regarding the diagnostic and clinical eval-
uation, as shown in Table 2. Also signs and symptoms
Table 1 Demographics and duration of disease in both groups at
baseline
K (n = 22) N (n = 24) P
Sex (female ⁄ male) 14 ⁄ 8 15 ⁄ 9 0.936
Age (median and quartile) 35 (29–45) 31.5 (25.5–41) 0.2477
Duration (median and quartile) 2 (0.25–8) 0.5 (0.25–6) 0.4324
Previous therapies(N ⁄ Y) 8 ⁄ 14 14 ⁄ 10 0.136
Comparison done by v2 test for nominal parameters or Mann–
Whitney for continuous variables.
533
E. M. Di Fonzo et al.

Table 2 Clinical evaluations at baseline in both groups Table 4 Clinical evaluations at 5 weeks follow-up in both groups
comparison on intention-to-treat basis
K (n = 22) N (n = 24) P
K (n = 17) N (n = 22) P
GACS Score 1 9 (41) 12 (50) 0.536
Score 2 13 (59) 12 (50) WoodÕs light 0 18 (100) 19 (100)
WoodÕs light 0 3 (14) 0 (0) 0.061 Mycological examination 0 18 (100) 19 (100)
1 19 (86) 24 (100) Complete resolution1 5 (29) 9 (47) 0.291
Mycological examination 0 2 (9) 1 (4) 0.499 Partial resolution1 12 (71) 9 (47)
1 20 (91) 23 (96) No change1 0 1 (6)
1
GACS: score 0 = normal skin, 1 = PV involvement <7% of total Data for one patient in K group is missing.
trunk area, 2 = PV involvement between 8 and 15% of total trunk Comparison done by v2 test.
area. Values in parentheses are percentages.
WoodÕs light: 0 = negative; 1 = positive. WoodÕs light: 0 = negative; 1 = positive.
Mycological examination 0 = negative; 1 = positive. Mycological examination 0 = negative; 1 = positive.
Comparison done by v2 test. Complete resolution: GAS score 0, negative WoodÕs light and
Values in parentheses are percentages. mycological examination.
Partial resolution: GAS score 1, negative WoodÕs light and myco-
logical examination.
in the two groups were similar in respect to scaling
(P = 0.651), itching (P = 0.287), hypo-pigmentation
(P = 0.488) and hyper-pigmentation (P = 0.204).
Table 5 Clinical evaluations at 3 months follow-up in both groups
Five weeks after the initiation of the treatment 18
patients (81%) in K group and 19 (80%) in N group K (n = 11) N (n = 13) P
returned for the follow-up visit. The total drop-out rate Complete resolution 9 (82) 12 (92) 0.439
was 19% (nine of 46: four in K group and five in N Partial resolution 2 (18) 1 (8)
group). No change 0 0
Complete resolution was observed in 29% of the
Complete resolution: GAS score 0, negative WoodÕs light and
patients in K group vs. 47% in N group (P = 0.291) as mycological examination.
reported in Tables 3 and 4. In addition 71% of patients Partial resolution: GAS score 1, negative WoodÕs light and myco-
in K group and 47% in N group had partial resolution, logical examination.
while 6% in the N group showed no change.
Signs of scale were absent in both groups, itching was
observed in 1 ⁄ 19 (6%) in N group, absence or light Ninety-one percent (20 ⁄ 22 patients in K group and
hypo-pigmentation in 10 ⁄ 18 (55%) in K vs. 14 ⁄ 19 21 ⁄ 23 in N group respectively) found the study
(73%) in N and light hyper-pigmentation in 1 ⁄ 18 (5%) medications extremely easy to use, in particular 9 ⁄ 15
in N. patients (60%) in K group vs. 6 ⁄ 12 (50%) in N group
In the N group an adverse event (urticaria) has been reported a higher acceptability compared to other drug
reported at the end of treatment, while no adverse formulations previously used, while 8 ⁄ 15 (53%) in K
events were reported for K group. group vs. 6 ⁄ 12 (50%) in N group found it more effective
(P = 0.863).
As reported in Table 5, at follow-up visit (3 months
Table 3 Clinical evaluations at 5 weeks follow-up in both groups
after treatment initiation), 9 ⁄ 11 patients (82%) in K
comparison on intention-to-treat basis, assigning to drop-outs
patients a GACS score 2 = worsening of disease and 12 ⁄ 13 patients (92%) in N showed persistent
complete resolution while two in K (18%) and one in N
K (n = 22) N (n = 24) P (8%) had a partial resolution (P = 0.439).
GACS Score 0 3 (14) 4 (17) 0.940
Score 1 7 (32) 8 (33)
Score 2 12 (54) 12 (50)
Discussion

GACS: score 0 = normal skin, 1 = PV involvement <7% of total

This study demonstrates that Ketomousse treatment is
trunk area, 2 = PV involvement between 8 and 15% of total trunk effective and safe as a standard and similar treatment for
area. PV, which contains a double ketoconazole concentra-
Comparison done by v2 test. tion. In addition the new drug is extremely well
Values in parentheses are percentages. tolerated with no adverse effects.

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534 Journal compilation  2008 Blackwell Publishing Ltd • Mycoses 51, 532–535

Different therapeutic options, both topical and sys-
temic, are available for the treatment of PV.
Ketomousse is a new thermophobic foam containing
ketoconazole 1%, an inhibitor of ergosterol biosynthesis
in the cell membrane of fungi and yeasts; 0.5% zinc
pyrithione, an antiproliferative ⁄ antifungal agent and
2% salicylic acid, an effective keratolytic agent.
A previous randomised study has shown Keto-
mousse with ketoconazole 1% to be significantly more
effective than ketoconazole 2% scalp fluid in the
treatment of moderate-to-severe dandruff, caused by
the same pathogenic agent as in the case of PV.
This is the first randomised study conducted to
evaluate Ketomousse efficacy in the treatment of PV,
after preliminary positive results were obtained in a pilot
study on 15 patients.
The results of this study suggest that excellent results
could be achieved even in this indication.
While the comparable clinical efficacy could be
ascribed to the potential synergistic effects of the three
components of Ketomousse credit must also be given
for the innovativeness of the formulation which, after
application, immediately releases the solvents allowing
a better delivery and penetration through the skin. The
technology of the foam preparation results in an easy
application, that could promote good patient compli-
ance and a rapid absorption of active molecules.
The cosmetic profile of Ketomousse (easy applica-
tion, formulation) was considered by patients equal or
slightly superior to other topical formulations, including
the ketoconazole 2% counterpart.
Only one patient in ketoconazole 2% group reported
an adverse event. This confirms the excellent safety
profile of Ketomousse formulation.
In conclusion, Ketomousse (ketoconazole 1%) dem-
onstrated to be equally effective and tolerated compared
with ketoconazole 2% with a slightly superior cosmetic
profile. Therefore Ketomousse could be considered an
excellent therapeutic option in the treatment of PV.
 2008 Mipharm S.p.A., Milan
Journal compilation  2008 Blackwell Publishing Ltd • Mycoses 51, 532–535
Ketomousse in pityriasis versicolor
Acknowledgments
The authors thank Tiziana Villa (from Mipharm S.p.A.)
because of whose great support, the present study has
been feasible. This work was supported by Mipharm
S.p.A. (Milan, Italy). S. Alvino, MD, an employee of
Mipharm S.p.A., was not involved in analysing the
study data prior to the drafting of the manuscript.
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