Randomized, Phase 2, Dose-Ranging Study in the Treatment of Rosacea With Encapsulated Benzoyl Peroxide Gel
June 2014 | Volume 13 | Issue 6 | Original Article | 685 | Copyright © June 2014
James J. Leyden MD
University of Pennsylvania, Philadelphia, PA
OBJECTIVE: Compare the safety and efficacy of 1% and 5% silica encapsulated benzoyl peroxide (E-BPO) in patients with papulopustular rosacea.
DESIGN: Multi-centered randomized, double blind, vehicle controlled parallel group, 12 week treatment in 92 patients with papulopustular rosacea. Primary endpoints were dichotomized IGA with success defined as clear/near clear and reduction in inflammatory lesions.
PATIENTS: 92 patients: 74% graded as moderate IGA, 14% severe and 12% mild. The mean inflammatory lesion count was 24.
INTERVENTION: Once daily treatment for 12 weeks with vehicle, 1% or 5% E-BPO.
RESULTS: 1% and 5% E-BPO were superior to vehicle in reducing papulopustular lesions P
=0.01 and P
=0.02. 5% E-BPO was superior to vehicle for IGA P
=0.0013. J Drugs Dermatol.
A subset of patients with rosacea developed papules and pustules (PPR),
which are currently viewed to be inflammatory follicular lesions.1,2 While recent
studies employing gene array profiles, immunohistochemical and molecular techniques have
helped define various pathways of inflammation, the stimulus or trigger for follicular
inflammation remains uncertain.3,4,5 The mite Demodex Folliculorum remains a most prominent
direct or indirect suspect.6,14 Current FDA approved therapies include topical metronidazole,
azelaic acid and systemic low dose doxycycline all of which are viewed to act as anti-inflammatory
agents.7,8,9 Two studies have shown the combination of benzoyl peroxide and clindamycin to be
effective in PPR with the combination more effective than clindamycin but not more effective
than benzoyl peroxide. In both studies there were patients who experienced difficulty tolerating
benzoyl peroxide. Despite a paucity of studies, clindamycin is widely believed to have in vivo
anti-inflammatory activity in acne and rosacea. Only one uncontrolled study was published in
which clindamycin was used as a mono therapy. As a result, the individual contribution of
benzoyl peroxide or clindamycin to the substantial
benefit reported from the combination of these two agents in PPR10,11 is not clear.
This study was conducted in compliance with Food and Drug Administration (FDA)
regulations, the ethical principles of the Declaration of Helsinki, and the current International
Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines.
Patients: 92 patients with PPR were enrolled (Table1). While a minimum
of 12 inflammatory lesions were required for entry into the study, the majority
of patients had a moderate IGA (74%) and 14% had a severe IGA The median number of
inflammatory lesions for each group was similar.
Vehicle 19.9%; 1% E-BPO, 28.6%; 5% E-BPO, 22.9%
Patients were treated once daily for 12 weeks with either vehicle, 1% or 5% E-BPO.
Patients were evaluated at base line and after 4, 8, and 12 weeks of therapy
for lesion counts and IGA. Signs of irritation were evaluated at
the latter time points and after 2 weeks cessation of treatment.
Primary efficacy endpoints were:Proportion of subjects with the primary measure of success; defined as a 2-grade improvement in
the IGA relative to baseline at week 12, with the week 12 IGA of clear or almost clear.Change in inflammatory lesion count at week 12
Secondary efficacy endpoints were:Proportion of subjects with a measure of success; defined as a 2-grade improvement in the IGA relative to baseline at week 12.IGA at week 12.Inflammatory lesion erythema assessment at week 12Rosacea erythema assessment at week 12Telangiectasia assessment at week 12
In this trial we studied the efficacy and safety of encapsulated BPO in
patients with PPR. Using a unique process, benzoyl peroxide12 is encapsulated in porous silicon dioxide (silica)