Pivotal Trial of the Efficacy and Safety of Oxymetazoline Cream 1.0% for the Treatment of Persistent Facial Erythema Associated With Rosacea: Findings from the First REVEAL Trial
January 2018 | Volume 17 | Issue 1 | Original Article | 97 | Copyright © January 2018
Leon H. Kircik MD,a Janet DuBois MD,b Zoe Diana Draelos MD,c Philip Werschler MD FAAD FAACS,d Kimberly Grande MD,e Fran E. Cook-Bolden MD,f Emily Weng ScD MBA,g David R. Berk MD,g and Gurpreet Ahluwalia PhDg
aDermResearch, PLLC, Louisville, KY bDermResearch, Inc., Austin, TX cDermatology Consulting Services, High Point, NC dPremier Clinical Research, Spokane, WA eThe Skin Wellness Center, Knoxville, TN fSkin Specialty Dermatology, New York, NY gAllergan plc, Irvine, CA
Abstract
An unmet need exists for a safe, tolerable, effective treatment for moderate to severe persistent facial erythema in patients with rosacea. This pivotal phase 3, multicenter, double-blind study evaluated the efficacy and safety of topical oxymetazoline in patients with facial erythema associated with moderate to severe rosacea. Patients were randomly assigned to treatment with oxymetazoline hydrochloride cream 1.0% or vehicle applied once daily for 29 days, and were followed for 28 days posttreatment. The primary efficacy outcome was having at least a 2-grade decrease from baseline on both the Clinician Erythema Assessment (CEA) and the Subject Self-Assessment for rosacea facial redness (SSA) scales (composite success) at 3, 6, 9, and 12 hours postdose on day 29. Safety assessments included treatment-emergent adverse events (TEAEs) and posttreatment worsening of erythema (composite CEA/SSA increase of 1-grade severity from baseline; rebound effect). A total of 440 patients (mean age, 49.5 years; 78.9% females) were randomized (oxymetazoline, n=222; vehicle, n=218); most had moderate erythema. On day 29, significantly greater proportions of oxymetazoline recipients achieved the primary efficacy outcome at each time point (P less than 0.02) and overall (P less than 0.001) compared with vehicle recipients. The incidence of discontinuation due to TEAEs was low in both groups (oxymetazoline group, 1.8%; vehicle group, 0.5%). The most common TEAEs reported during the entire study period were application-site dermatitis, application-site erythema, and headache in the oxymetazoline group (1.4% each), and headache (0.9%) in the vehicle group. Following cessation of treatment, low proportions of patients experienced rebound effect (oxymetazoline group, 2.2%; vehicle group, 1.1%). Oxymetazoline applied to the face once daily for 29 days was effective, safe, and well tolerated in patients with moderate to severe persistent facial erythema of rosacea.
J Drugs Dermatol. 2018;17(1):97-105.
INTRODUCTION
Rosacea is a chronic dermatologic condition affecting approximately 16 million individuals in the United States.1-3 The most common clinical feature of rosacea is persistent erythema present on the central face; other common features include flushing, papules or pustules, and telangiectasia.2 Symptoms may include burning, stinging, dry patches, edema, and ocular manifestations. Rosacea is associated with a substantial psychosocial burden and negative effect on quality of life.4 Pharmacologic treatments approved by the US Food and Drug Administration (FDA) for papules and pustules of rosacea have no therapeutic effect on persistent erythema that remains after inflammatory lesions have cleared; thus, limited treatment options are available Persistent erythema associated with rosacea is thought to occur because of dysregulation in the cutaneous vasomotor response resulting in chronic abnormal dilation of the facial blood vessels.6 Activation of α1- and α2-adrenoceptors on smooth muscle of blood vessels results in vasoconstriction that may improve persistent erythema associated with rosacea.5 Clinical trials have evaluated α1- and α2-adrenoceptor agonists for the treatment of this condition.7,8 Two products are approved by the FDA for the treatment of adults with persistent facial erythema of rosacea, oxymetazoline hydrochloride cream, 1.0% (Rhofade™, Allergan plc, Dublin, Ireland), an α1A-adrenoceptor agonist that causes vasoconstriction of the cutaneous microvasculature,6,9,10 and brimonidine topical gel, 0.33% (Mirvaso®, Galderma Laboratories, Fort Worth, TX), a selective α2-adrenoceptor
