Randomized, Double-Blind, Split-Face Study to Compare the Irritation Potential of Two Topical Acne Formulations Over a 21-Day Treatment Period

February 2016 | Volume 15 | Issue 2 | Original Article | 178 | Copyright © February 2016

Leon H. Kircik MD,a Varsha Bhatt PhD,b Gina Martin MOT,b and Radhakrishnan Pillai PhDb

aIcahn School of Medicine at Mount Sinai, New York, NY; Indiana University School of Medicine, Indianapolis, IN; Physicians Skin Care, PLLC, Louisville, KY
bDow Pharmaceutical Sciences, a Division of Valeant Pharmaceuticals North America LLC, Petaluma, CA

Abstract
The use of fixed combinations in acne vulgaris (acne) is very common, however comparative clinical trial data are limited. Cutaneous tolerability can influence patient compliance, and concerns about skin irritation with topical acne treatments have lead to a number of comparative split-face studies.
Recently, a new fixed combination product was introduced (clin 1.0%-BP 3.75% gel) that was shown to be effective in reducing both inflammatory and noninflammatory lesions in moderate to severe acne. Here, we assess the tolerability of clin 1.0%-BP 3.75% gel compared with adap 0.1%-BP 2.5% gel in healthy volunteers with no apparent facial redness or dryness over 21-days, using a split-face methodology.
Especially over the first two weeks of treatment, clin 1.0%-BP 3.75% gel was more tolerable than adap 0.1%-BP 2.5% gel, with statistically significant differences in cumulative change from baseline starting as early as day 8 (dryness) and day 9 (erythema), and composite index on days 8-12 and 16. Transepidermal water loss was less with clin 1.0%-BP 3.75% gel, although the difference was not statistically significant.

J Drugs Dermatol. 2016;15(2):178-182.

INTRODUCTION

The use of fixed combinations with benzoyl peroxide (BP) and either a retinoid such as adapalene (adap), or antibacterial such as clindamycin (clin), are commonplace in the management of acne vulgaris (acne). Comparative efficacy data are limited, although in a study of 337 patients with mild-to-moderate acne clin 1.0%-BP 5% (with hydrating excipients) demonstrated a barely statistically significant superiority (P=.046) and more rapid treatment success (P=.035) when compared with adap 0.1%-BP 2.5%.1 In addition, clin 1.0%-BP 5% demonstrated a better tolerability profile, with fewer treatment-related adverse events (AEs).1
Cutaneous safety and tolerability of topical medications has been suggested as a key determinant in patient compliance. A 3-week randomized split-face study in 60 healthy participants to determine the optimal combination of adap and BP regarding irritation potential reported better cutaneous tolerability for adap 0.1%-BP 2.5% than adap 0.1%-BP 5%, and similar profile to BP 2.5% (P=.088) or BP 5% (P=.061) monotherapy. Adap 0.1%-BP 5% induced significantly more irritation than BP 5% monotherapy (P<.001).2
A number of split-face and cumulative irritation studies have demonstrated inferior cutaneous tolerability of adap 0.1%-BP 2.5% to other therapy options in acne patients.3-8 A 2-week single-blind split-face study in 48 patients with mild-to-severe facial acne showed clin 1.0%-BP 5% to have a better tolerability profile to adap 0.1%-BP 2.5% following daily treatment; with irritation, dryness and erythema all significantly less common (P≤.001), and 63% - 64% of patients expressing a preference for the clindamycin combination at week 1 and week 2 respectively.3 Treatment related AEs were significantly less common with clin 1.0%-BP 5%. Pooled results of two single-blind split-face studies enrolling 76 patients with mild-to-moderate acne found clin 1.0%-BP 2.5% to have statistically better tolerability (P<.03) during the first two weeks of treatment when compared with adap 0.1%-2.5%.4
A 2-week randomized, observer-blind, split-face study in acne patients assessed the irritation potential and likelihood of continued use of adap 0.1%-BP 2.5% and clin 1.0%-BP 2.5%. Irritation potential was more pronounced and severe with adap 0.1%-BP 2.5% (P<.05 from day 6). Patients reported clin 1.0%-BP 2.5% was better absorbed, dried more quickly, moisturized/hydrated better, was less likely to sting or burn and left the face smoother/softer.5 A three-week single-blind study assessed the irritation potential of adap 0.1%-BP 2.5% and tretinoin gel microsphere 0.04% in a panel of 170 subjects.8 Tretinoin gel microsphere 0.04% was associated with better facial tolerance with significantly less cumulative erythema, dryness, burning/stinging and itching (all P<.0001).8
Clindamycin 1.0%-benzoyl peroxide 3.75% gel (clin 1.0%-BP 3.75%) has been shown to be effective in moderate to severe acne, with a very low irritation potential.9 The objective of our