Tolerability and Irritation Potential of Four Topical Acne Regimens in Healthy Subjects

June 2013 | Volume 12 | Issue 6 | Original Article | 644 | Copyright © June 2013

Gary Grove PhD,a Charles Zerweck PhD,a and Jennifer Gwazdauskas MBAb

acyberDERM Clinical Studies, Lawrence Park Industrial Park, Broomall, PA bStiefel, a GSK company, Research Triangle Park, NC

Abstract
Benzoyl peroxide (BPO) is a cornerstone of acne therapy, often used in combination with a topical antibiotic and/or a retinoid. Three independent 2-week studies were conducted in healthy subjects to compare the tolerability and irritation potential of topical treatment with Duac® Gel (BPO 5%–clindamycin phosphate 1.2%) vs Acanya® Gel (BPO 2.5%–clindamycin phosphate 1.2%), Aczone® Gel (dapsone 5%), or Epiduo® Gel (BPO 2.5%–adapalene 0.1%). For each study, subjects were randomized to apply one of the comparative products on one side of the face; the contralateral side remained untreated. Primary (erythema and dryness) and secondary tolerability assessments were performed throughout the study. Independent blinded expert grader assessments of erythema found no significant overall difference between any of the comparative groups. Treatment with Epiduo Gel resulted in a significant increase in dryness and evaporative water loss values compared with Duac Gel. Overall, subject self-assessments were equally favorable across all study groups, although the Epiduo Gel group reported a higher frequency of adverse perceptions (ie mild burning/stinging). In conclusion, the four topical acne medications tested were well tolerated throughout the study period. Treatment with Epiduo Gel resulted in a significant increase in dryness, evaporative water loss, and sensations of burning and stinging. No other significant differences in self-assessment perceptions were observed between treatments.

J Drugs Dermatol. 2013;12(6):644-649.

INTRODUCTION

Benzoyl peroxide (BPO) is a cornerstone of acne therapy that is often used in combination with a topical antibiotic and/or a retinoid. The use of varying concentrations of BPO with an antibiotic such as clindamycin (as clindamycin phosphate 1.2%) minimizes the emergence of antibacterial resistance1 while enhancing efficacy compared with the individual agents.2,3 Furthermore, topical fixed-dose combinations of BPO and clindamycin phosphate 1.2% possess very low irritation potential4,5 and are often better tolerated than either agent alone.3 Improved tolerability of a fixed-combination of BPO–clindamycin phosphate 1.2% has also been demonstrated in combination with a retinoid.6
The tolerability and efficacy of topical fixed-dose combinations of low-strength BPO (2.5%) with either clindamycin phosphate 1.2% (Acanya® Gel)7–9 or adapalene 0.1% (Epiduo® Gel) have been widely demonstrated.10–14 The antibacterial dapsone 5% gel (Aczone® Gel) used alone15,16 or in combination with BPO (4%)17 is also an effective and well tolerated acne treatment.18 Acanya Gel results in less irritation than a higher concentration of BPO (5%) in combination with clindamycin phosphate 1.2% (Duac® Gel).19 No studies have compared the safety and tolerability of Duac Gel with Epiduo Gel or Aczone Gel.
The primary objectives of the three studies described here were to evaluate the tolerability and irritation potential of Duac Gel compared with Acanya Gel, Aczone Gel, or Epiduo Gel. Secondary objectives included assessment of potential changes in the integrity of the stratum corneum barrier and skin surface hydration after each treatment, and estimation of subject tolerability through skin assessment questionnaire and Product Acceptability and Preference Questionnaire.

METHODS

Eligible Subjects

Three independent single-blind, single-center, parallel group, randomized, 2-week studies were conducted between May and September 2009 in healthy subjects to evaluate the tolerability and irritation potential of topical Duac Gel (BPO 5%– clindamycin phosphate 1.2%) compared with Acanya Gel (BPO 2.5%–clindamycin phosphate 1.2%), Aczone Gel (dapsone 5%), or Epiduo Gel (BPO 2.5%–adapalene 0.1%).
Eligible volunteers (screened 3 days prior to randomization) were males and females aged 18 to 45 years who did not have facial acne, and had a Fitzpatrick Skin Type of I, II, or III. All study procedures and protocols were reviewed and approved by the institutional review board in accordance with the International Conference on Harmonization Good Clinical Practice Guidelines, Good Laboratory Practice Guidelines, and COLIPA (European Cosmetics Trade Association) Efficacy Testing Guidelines (Study numbers NCT01015638, NCT00964366, and NCT00926367; www.clinicaltrials.gov).