Onset of action and efficacy of novel clindamycin 1%/tretinoin 0.025% formulation for acne vulgaris

P6136Natural modulation of PAR-2 and TLR2: Application to clinical acne skincare

Nadege Lachmann, Laboratoires Expanscience, Epernon, France; BernardChadoutaud, Clinreal Online, Toulouse, France; Bernard Cribier, UniversiteLouis Pasteur, Strasbourg Cedex, France; Caroline Baudouin, LaboratoiresExpanscience, Epernon, France; Franck Menu, Laboratoires Expanscience,Epernon, France; Marjorie Biassette, Laboratoires Expanscience, Epernon,France; Philippe Msika, Laboratoires Expanscience, Epernon, France

Inflammation plays a central role in acne. A global acne skin care product has beenformulated with active principles: quinoa peptides (natural PAR-2 modulator), 5-alfaavocuta, zinc gluconate, capryloyl glycine, and long lasting alfa hydroxy acidderived. In vitro studies on 5-alfa avocuta in dermal fibroblasts significantly inhibitedtype 1 5-alfa reductase activity (-49%). In keratinocytes treated with a synthetic TLR2(Toll-like receptor) ligand mimicking Propinobacterium acnes lipoprotein, itreduced the TLR2 gene overexpression (-52%), contributing to counteract the Pacneseinduced inflammatory cascade. Quantification of UV P acnesederivedporphyrines fluorescence 22 acneic patients, aged 11 to 40, applied the testedproduct twice a day for 30 days during an open study. VISIA CR coupled tocomputerized analysis demonstrated a 30% decrease of bacterial activity. A singleblind comparative randomized study performed under dermatologic control in-cluded 126 female patients (15-35 years old) with light to moderate acne (# 12retentional and 5 to 9 inflammatory lesions). Sixty-four applied tested product and62 a referenced product twice daily for 90 days. There were no statistic differencebetween both groups at D45 and D90. Tested product decreased inflammatory(respectively -50% and -70.3%) and retentional (-40.2%/-57.3%) lesions (P \ .01).Investigator Global Assessment (IGA) confirmed an improvement in 89% of patients,79.6% $ 50%. Seborrhea and postlesional erythema were reduced by 38.5% and35.1% at D45 (P\.01) and by 56.4% and 51.4% at D90 (P\.01). Tolerance wasexcellent in 98% of cases.

Conclusion: The use of a product targeting key acneic pathways (inflammationreceptors, hyperseborrhea, hyperkeratinization) with active principles from naturaltechnology leads to a significant global improvement in mild to moderate acne.

APRIL 20

cial support: None identified.

P6406Onset of action and efficacy of novel clindamycin 1%/tretinoin 0.025%formulation for acne vulgaris

Brigitte Dr�eno, MD, PhD, Nantes University, Nantes, France; Alison Layton,MBChB, Harrogate and District NHS Foundation Trust, Harrogate, UnitedKingdom

Background: Many treatments are available for acne vulgaris, including monothera-pies, such as topical retinoids and antibiotics, and combinations of these therapies.Patient adherence with medications is often poor for a variety of reasons, includingadverse effects, handling, or convenience issues, lack of efficacy, and slow onset ofaction. Poor adherence is a common cause of treatment failure. The aim of thisanalysis was to determine the onset of action and efficacy of a novel gel formulationcontaining clindamycin 1%/tretinoin 0.025% (Clin-RA) and its components in 2studies.

Methods: Inflammatory and noninflammatory lesion counts at weeks 2, 4, 8, and 12were analysed in 2 identical, randomized, double-blind, parallel group phase IIIstudies of Clin-RA, both monotherapies and vehicle (study 1 and 2). The onset ofaction of each component was defined as the first time point fromwhich there was astatistically significant difference in the % change in lesion count versus vehicle thatwas sustained for the rest of the study.

Results: Clin-RA had a rapid onset of action against inflammatory andnoninflammatory lesions (week 2; P # .0423): 6 weeks faster than tretinoinagainst inflammatory lesions, and 10 weeks faster than clindamycin againstnoninflammatory lesions. Tretinoin had a rapid onset of action againstnoninflammatory lesions in both studies (study 1: week 4 [P ¼ .0006]; study2: week 2 [P ¼ .0065]); this was 8 to 10 weeks faster than the action ofclindamycin against these lesions (week 12: both studies, P # .0232).Clindamycin had a rapid onset of action against inflammatory lesions (week2; P # .0016); this was 6 to 10 weeks faster than tretinoin’s onset ofaction against these lesions (study 1: week 8 [P ¼ .0036]; study 2: week 12[P ¼ .0146]). There were no new safety or tolerability concerns with Clin-RAwith the incidence of adverse events being comparable to its individualmonotherapies.

Conclusion: These results show that Clin-RA is 6 to 10 weeks faster than itscomponents at reducing inflammatory and noninflammatory lesions. Its compo-nents have complementary actions with clindamycin having a rapid onset againstinflammatory and tretinoin against noninflammatory lesions. This quick responsecould be of interest for increasing the adherence of acne patients, specificallyteenagers.

ported by Meda Pharma GmbH and Co KG.

13

P6356Patient satisfaction with a fixed dose combination of adapalene-benzoylperoxide gel as part of a regimen and used alone as maintenance therapy

Robert T. Brodell, MD, Northeastern Ohio Medical University, Rootstown, OH,United States; Albert Wertheimer, PhD, Temple University, Philadelphia, PA,United States; Darryl Toth, MD, XLR8 Medical Research, Inc, Windsor, Ontario,Canada; Delphine Bucher, Galderma International, La D�efense, France; ElyseRafal, MD, Derm Research Center of New York, Inc, Stony Brook, NY, UnitedStates; Nabil Kerrouche, PhD, Galderma Research and Development, SNC, Biot,France; Stephen Tyring, MD, Center for Clinical Studies, Webster, TX, UnitedStates

Acne vulgaris is a common inflammatory disease of the skin. Traditional clinicaloutcomes in studies of patientswith acne vulgaris, such as lesion counts, may or maynot correlate with patient satisfaction with treatment. Patient satisfaction wasassessed in 2 clinical trials investigating a combination product of adapalene-benzoylperoxide 0.1%/2.5% (A-BPO) gel as initial treatment as part of a regimen and then asmaintenance therapy. The first study enrolled patients for 12 weeks who wererandomized to receive doxycycline 100 mg once daily and either A-BPO or vehicle.Patients with at least good improvement in either arm were eligible for a secondstudy. Patients were subsequently rerandomized to either A-BPO or vehicle as a 24-week maintenance therapy. At the end of the first study, patients responded tosurvey questions and indicated they were significantly satisfied with the A-BPOtreatment in 5 of 6 questions (P \ .001). Patients surveyed at the end of thesecond related study were also significantly satisfied with A-BPO in 4 of 5 questions(P \.001). There was no significant difference in being bothered by side effectsbetween treatment groups in either study (P [ .05). The high levels of patientsatisfaction with A-BPO treatment suggest that it is likely to be well accepted bypatients as topical therapy usedwith an oral antibiotic and as amaintenance therapy.

d by Galderma Research and Development, SNC.

P6035Photodynamic therapy with methylaminolevulinate 80 mg/g and red lightdemonstrates significant efficacy in acne

David Pariser, MD, Eastern Virginia Medical School, Norfolk, VA, United States

Aim: To investigate efficacy and safety of methylaminolevulinate (MAL) at 80mg/g vsvehicle cream followed by red light illumination in severe acne patients.

Methods: Multicenter, randomized, double-blind, vehicle-controlled study. A total of153 male and female patients aged 12 to 35 years were enrolled at 15 sites in the UShaving Fitzpatrick skin types I through VI, 25 to 75 inflammatory and 20 to 100noninflammatory acne lesions, no more than 3 nodules on the face and anInvestigator’s Global Assessment (IGA) score of 4. MAL or vehicle cream wasapplied on the skin and left to incubate under occlusion for 1.5 hours beforeillumination with a light dose of 37 J/cm2 (red light with average wavelength of 632nm) using a lamp with a total of 512 light emitting diodes (LEDs) covering an area ofapproximately 32 cm3 18 cm. All patients received 4 treatments 2 weeks apart (atweeks 0, 2, 4, and 6). The primary endpoint was reduction of inflammatory lesions 6weeks after the last treatment (week 12). Secondary endpoints were proportion ofpatients with success according to IGA (success defined as an improvement of atleast 2 grades from baseline), reduction in noninflammatory lesions, pain duringillumination using a Visual Analogue Scale (VAS) from 0 to 10 and erythema score.

Results: Patients treated with MAL had a statistically significant reduction ininflammatory lesions of 43.8% as compared to 26.6% in the vehicle group (P ¼.003). MAL showed a statistically significant improved IGA treatment success ratecompared to vehicle, 44.0% versus 26.4% (P ¼ .013). A comparable reduction innoninflammatory lesions was achieved in both groups (P ¼ .853). Posttreatmenterythema was reported more frequently in the MAL group (89% vs 70%), whichgenerally subsided by the following day. Twelve patients withdrew from the studybecause of adverse events. Six (6%) patients in the MAL group withdrew because ofpain-related adverse events (pain, burning, or stinging). No serious adverse eventswere reported in the study.

Conclusion: MAL significantly decreased the number of inflammatory lesions andsignificantly improved IGA success rate. Comparable efficacy was demonstrated inreducing noninflammatory lesions and the treatment was well tolerated.

d by a grant from Photocure ASA, Olso, Norway.

J AM ACAD DERMATOL AB17