Adapalene 0.1% Lotion in the Treatment of Acne Vulgaris: Results From Two Placebo-controlled, Multicenter, Randomized Double-blind, Clinical Studies

June 2010 | Volume 9 | Issue 6 | Original Article | 639 | Copyright © June 2010

Lawrence F. Eichenfield MD,a Michael Jarratt MD,b Joel Schlessinger MD,c Steven Kempers MDd, Vasant Manna MDe, Joyce Hwa RN BSNe, Yin Liu PhDe, Michael Graeber MDe, on Behalf of the Adapalene Lotion Study Group

aUniversity of California, San Diego and Rady Children’s Hospital, San Diego, CA bDermResearch Incorporated, Austin, TX cAdvance Skin Research Center, Omaha, NE dMinnesota Clinical Study Center, Fridley, MN eGalderma Research and Development, Cranbury, NJ

Abstract
Background: Acne vulgaris is a common chronic skin disease affecting roughly 15 percent of the general population and up to 85 percent of adolescents and young adults. Adapalene, a synthetic naphthoic acid derivative with retinoid activity, has demonstrated good clinical efficacy in the treatment of acne if used with full compliance.
Objectives: To evaluate the efficacy and assess safety of a new adapalene formulation, adapalene 0.1% lotion, versus the lotion vehicle in subjects with acne vulgaris.
Methods: Subjects were randomized to receive either adapalene 0.1% lotion or its vehicle once daily for 12 weeks in two multicenter, randomized, vehicle-controlled, double-blind, parallel group studies. Efficacy was evaluated using two co-primary endpoints: Investigator Global Assessment (IGA) of success rate (defined as the proportion of subjects who achieved at least a two point reduction, on a 5-point scale, from baseline to week 12 in IGA score); and the absolute change from baseline to week 12 in total, inflammatory and non-inflammatory lesions. Signs of local skin irritation and routine clinical safety parameters were evaluated throughout both studies.
Results: In total, 2,141 subjects were included in the two studies: 1,068 patients received adapalene 0.1 percent lotion and 1073 received the vehicle. In both studies, adapalene 0.1% lotion was shown to be significantly more effective than its vehicle in improvement in the IGA success rate. Adapalene 0.1% lotion was also significantly superior to its vehicle in all three lesion reduction measures: total, inflammatory and non-inflammatory. Reports of application site skin irritation in the adapalene 0.1% lotion treatment group were transient and mild or moderate in severity, with only a few being severe. Additionally, according to patient surveys, the lotion formulation was found to be easily spreadable, easily absorbed and pleasant to use.
Conclusion: Adapalene 0.1% lotion used once a day for 12 weeks is effective and well tolerated in the treatment of acne vulgaris.

INTRODUCTION

Acne vulgaris is a common skin disorder, affecting up to 85 percent of adolescents.1 The disorder is chronic, usually beginning with the onset of puberty, and is characterized by episodes of recurrence. Acne also appears frequently in adults, with estimates of prevalence ranging from 12–17 percent in adult females and one to 12 percent in adult males.2 Recently updated consensus guidelines for the treatment of acne emphasize the potential for physical scarring such as persistent hyperpigmentation and pitted or nodular hypertrophic scars. Once present, these cosmetic disfigurements are difficult and expensive to treat. Additionally, severe acne can cause emotional and psychological scarring. Potential psychological sequelae can include anxiety, social withdrawal and depression.3,4 Because of this potential for physical and psychological scarring, experts recommend early and aggressive treatment of acne.4
Acne is caused by the interaction of several pathogenic factors. Androgen-stimulated increase in sebum production combined with increased cohesion and hyperproliferation of keratinocytes leads to the formation of the microcomedo, the precursor to all acne lesions.4 Clinically obvious open or closed comedones form with continued hyperproliferation of follicular keratinocytes. Propionibacterium acnes (P. acnes) proliferates in the lipid-rich anerobic environment of the blocked follicle and produces several inflammatory modulators capable of activating the skin’s innate immune response.5 Recognition of bacte-