P6178Efficacy and safety of once-daily brimonidine tartrate gel 0.5% for mod-erate to severe facial erythema of rosacea: Two randomized, double-blind,and vehicle-controlled phase III studies

Joseph F. Fowler, MD, University of Louisville, Louisville, KY, United States;Angela Moore, MD, Arlington Center for Dermatology, Arlington, TX, UnitedStates; Kappa Meadows, MD, The Education and Research Foundation, Inc,Lynchburg, VA, United States; Mark Jackson, MD, University of Louisville,Louisville, KY, United States; Matthew Leoni, MD, Galderma Research andDevelopment, RNC, Cranbury, NJ, United States; Michael T. Jarratt, MD,DermResearch, Inc, Austin, TX, United States; Terry Jones, MD, J&S Studies,Inc, Bryan, TX, United States

No prescription drug is currently approved in the United States for treating theerythema associated with rosacea. Two phase III studies evaluated the efficacy andsafety of brimonidine tartrate (BT), a highly selective a2-adrenergic agonist andvasoconstrictor, reduces facial erythema when applied once-daily topically. Thestudies were multicenter, randomized, double-blind, vehicle-controlled compari-sons. Subjects with moderate to severe facial erythema, according to a clinician’serythema assessment (CEA) and a patient self-assessment (PSA), were randomized ina 1:1 ratio. They received BT gel 0.5% or vehicle once-daily for 4 weeks, with a 4-week follow-up. The primary efficacy endpoint was success profile on day 29,defined as a 2-grade improvement in CEA and PSA over 12 hours. The secondaryefficacy endpoint was 1-grade improvement on CEA and PSA 30 minutes after thefirst application on day 1. Safety endpoints were also evaluated. Similar efficacy andsafety was observed in both studies. BT had a significantly superior success profilecompared to vehicle on days 29, 15, and 1. BT had a significantly superior successprofile compared to vehicle on days 1, 15, and 29. No evidence of tachyphylaxis,rebound, or aggravation of other disease signs was seen. The incidence of adverseevents (AEs) related to BTwas equivalent to or slightly higher than that observed forvehicle (study 1, 9.5% and 9.7%; study 2, 11.6% and 5.3%). Most treatment relatedAEs were transient, mild to moderate in intensity, and dermatologic in nature. Once-daily BT 0.5% was shown to provide significantly greater efficacy compared tovehicle for the treatment of moderate to severe erythema associated with rosaceawith a comparable safety and tolerability profile.

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d by Galderma Research and Development, SNC.

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P6857Evaluating clinical trial design: Systematic review of randomized vehicle-controlled trials for determining efficacy of benzoyl peroxide topicaltherapy for acne

Sonia Lamel, MD, University of California San Francisco, San Francisco, CA,United States; Howard Maibach, MD, University of California San Francisco, SanFrancisco, CA, United States; Maral Rahvar, MD, University of California SanFrancisco, San Francisco, CA, United States; Raja Sivamani, MD, University ofCalifornia Davis, Sacramento, CA, United States

Background: Determined efficacies of investigational drugsbenzoyl peroxidemay beaffected by study design, implementation, and vehicle effects. We evaluated rates ofactive treatment and vehicle responders in randomized, controlled trials assessingthe efficacy of topical benzoyl peroxide to treat acne. We evaluated for sought toelucidate areas to that may allow improvement in accuracy of determiningaccurateed treatment efficacies.

Methods:We conducted a systematic review of randomized, vehicle-controlled trialsevaluating the efficacy of topical benzoyl peroxide for the treatment of acne. Wecompared the response rates of the vehicle treatment arms versus those in the activedrug benozyl peroxide arms achieving treatment response.

Results: Twelve trials met inclusion criteria, with 2818 patients receiving benzoylperoxide monotherapy treatment and 2004 receiving vehicle treatment. Theaverage percent reduction in total number of acne lesions was 44.3 (SD ¼ 9.2)and 27.8 (SD ¼ 21.0) for the active and vehicle treatment groups, respectively. Theaverage reduction in noninflammatory lesions was 41.5% (SD ¼ 9.4) in the activetreatment group and 27.0% (SD ¼ 20.9) in the vehicle group. The average percentdecrease in inflammatory lesions was 52.1 (SD ¼ 10.4) in the benzoyl peroxidegroup and 34.7 (SD ¼ 22.7) in the vehicle group. The average percentage ofparticipants achieving success per designated study outcomes was 28.6 (SD¼ 17.3)and 15.2 (SD ¼ 9.5) in the active treatment and vehicle groups, respectively.

Limitations: Limited number of randomized vehicle controlled trials evaluatingbenzoyl peroxide.

Conclusion: Patient responses in randomized, controlled trials evaluating topicalacne therapies may be affected by clinical trial design, implementation, the biologiceffects of vehicles, and natural disease progression. ‘‘No treatment’’ groups arenecessary to determine accurate treatment efficacies.

cial support: None identified.

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P6599Ex vivo demonstration of a synergistic effect of adapalene and benzoylperoxide on inflammatory acne lesions

Amir Khammari, PhD, Nantes University Hospital, Nantes Cedex 1, France; Anne-Chantal Knol, PhD, Nantes University Hospital, Cedex, France; Brigitte Dr�eno,MD, PhD, Nantes University Hospital, Cedex, France

The success of a retinoid applied with benzoyl peroxide (BPO) in treating acne hasbeen well documented but with no understanding of what contributes to the effectsseen clinically. This ex vivo study investigated the mechanisms associated with thiseffect when adapalene and BPO are incubated in combination or alone onkeratinocyte proliferation/differentiation markers and inflammatory markers histo-chemically in skin biopsy specimens of patients with acne. These markers wereassessed in 7 men and women, over the age of 18, with acne vulgaris on their backs.Subjects underwent 5 skin punch biopsies, including 1 in an area clinically free ofacne. Subjects returned 9 days later for wound assessment. Immunohistochemistryshowed that proliferation and differentiation markers (Ki-67, integrin a2, a3, anda6) and innate immunity markers (TLR-2, b-defensin 4, and IL-8) were overex-pressed in inflammatory acne skin compared to uninvolved acne skin. Whenadapalene was incubated with BPO the combination inhibited epidermal prolifer-ation of a2 and a6 integrins to levels close to uninvolved skin. Adapalene with BPOalso down-regulated expression of TLR-2, hBD-4, and IL-8. When skin biopsies wereincubated alone with adapalene, adapalene decreased TLR-2, but had no effect onhBD-4 and IL-8. BPO alone had no effect on TLR-2. The study revealed that ex vivoincubation of adapalene and BPO in skin biopsies of acne patients has a synergisticeffect on certain abnormal epidermal proliferation/differentiation and inflammationmarkers in acne lesions versus adapalene or BPO alone.

d by Galderma Research and Development, SNC.

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P6635Gene expression data provides evidence that decylene glycol can benefi-cially affect acne and normalize responses of keratinocytes to bacteria

Robert L. Binder, PhD, Procter and Gamble Beauty, Cincinnati, OH, United States;Jun Xu, PhD, Procter and Gamble Beauty, Cincinnati, OH, United States; RaghuKainkaryam, PhD, Procter and Gamble Beauty, Cincinnati, OH, United States;Scott M. Hartman, MS, Procter and Gamble Beauty, Cincinnati, OH, United States

Background: Global gene expression profiles can serve as surrogates or indicators ofphenotypes, and through patternmatching it is possible to use gene expression datato link biologic states. Two of the authors (R.K. and J.X.) have developed a new geneexpression pattern matching algorithm called FaceMap that is based on analyticapproaches used for facial recognition. We have applied FaceMap to link geneexpression profiles induced by chemicals in cultured cells to clinical acne data andresponses induced in keratinocytes by bacteria.

Objective: To use gene expression profiling and FaceMap to investigate the activitiesat the gene expression level of decylene glycol (1, 2-decanediol). This work wasmotivated by evidence that decylene glycol (DG) has broad spectrum antimicrobialactivity, including against Propinobacterium acnes, and antiirritant properties inskin.

Methods: Human telomerized keratinocytes and BJ fibroblasts were treated with aproprietary preparation of DG for 6 hours. RNA was isolated, and gene expressionprofiling was conducted by standard methods using Affymetrix GeneChips. The DGdata were added to a large set of expression profiles induced by other chemicals insimilar experiments and compared using FaceMap analysis to published clinicalgenomics data on acne obtained from the Gene Expression Omnibus (GEO)database, which is a public repository of genomics data. Comparisons were alsomade to a series of experiments obtained from GEO in which oral keratinocyteswere treated with either pathogenic or commensal bacteria.

Results: FaceMap analysis yields a distance measure for each of the materials testedcompared to the respective conditions. Materials that tend to mimic the conditionwill have positive scores and materials that tend to reverse the pattern of geneexpression in the condition (predicted to be beneficial) will have negative scores.DG linked negatively to acne in a dose-dependent manner. A reference material,cantharidin, which is an extremely potent irritant, linked strongly positively to thiscondition, supporting the validity of the DG results. DG also linked negatively to theexpression profiles induced in oral keratinocytes by pathogenic bacteria, andpositively to the profiles induced by commensal species. These results provideevidence that DG will beneficially affect acne skin and tend to normalize theresponses of keratinocytes to bacteria.

nsored by Procter and Gamble.

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