Phase 2 Randomized, Dose-Ranging Study of Oxymetazoline Cream for Treatment of Persistent Facial Erythema Associated With Rosacea

March 2018 | Volume 17 | Issue 3 | Original Article | 308 | Copyright © March 2018


Janet DuBois MD,a Jeffrey S. Dover MD FRCPC,b Terry M. Jones MD,c Robert A. Weiss MD FAAD FACPh,d David R. Berk MD,e and Gurpreet Ahluwalia PhDe

aDermResearch, Inc., Austin, TX bSkinCare Physicians, Chestnut Hill, MA cDermataloge, Bryan, TX dMD Laser Skin & Vein Institute, Hunt Valley, MD eAllergan plc, Irvine, CA

Abstract
Background: Rosacea is a chronic dermatologic condition with limited treatment options. Objective: This phase 2 study evaluated the optimal oxymetazoline dosing regimen in patients with moderate to severe persistent facial erythema of rosacea. Methods: Patients were randomly assigned to oxymetazoline cream, 0.5%, 1.0%, or 1.5%, or vehicle, administered once daily (QD) or twice daily (BID) for 28 consecutive days. The primary efficacy endpoint was the proportion of patients with ≥2-grade improvement from baseline on the Clinician Erythema Assessment (CEA) and the Subject Self-Assessment of erythema (SSA-1) on day 28. Safety assessments included treatment-emergent adverse events and dermal tolerability. Results: A total of 356 patients were treated (mean age, 50.0 years; 80.1% female). The proportions of patients achieving the primary endpoint were significantly higher with oxymetazoline 0.5% QD (P=0.049), 1.0% QD (P=0.006), 1.5% QD (P=0.012), 1.0% BID (P=0.021), and 1.5% BID (P=0.006) versus their respective vehicles. For both QD and BID dosing, the efficacy of oxymetazoline 1.0% was greater than the 0.5% dose and comparable to the 1.5% dose. Safety and application-site tolerability were similar across groups. Limitations: Short-term treatment period. Conclusion: Oxymetazoline 1.0% QD provided the optimal dosing regimen and was selected for evaluation in phase 3 clinical studies. J Drugs Dermatol. 2018;17(3):308-316.

INTRODUCTION

Rosacea, a chronic dermatologic condition that affects approximately 16 million adults in the United States, is characterized by persistent erythema, flushing, telangiectasia, and inflammatory papules and pustules.1-3 Persistent erythema is the most common sign of rosacea, and is often associated with social embarrassment and psychological distress.4-6 Limited treatment options are available for persistent facial erythema of rosacea, as most topical pharmacological agents reduce inflammatory lesions of rosacea and perilesional erythema, but have no therapeutic effect on persistent erythema.7Activation of post-synaptic a1- and a2-adrenoceptors results in vasoconstriction that may improve persistent erythema of rosacea; consequently, a1- and a2-adrenoceptor agonists have been investigated clinically for treatment of this chronic dermatologic condition.8,9 Until recently, brimonidine gel 0.33%, a highly selective a2-adrenoceptor agonist, was the only product approved by the US Food and Drug Administration (FDA) for treatment of persistent facial erythema of rosacea.3,10 Oxymetazoline, an a1A-adrenoceptor agonist that results in vasoconstriction of the cutaneous microvasculature,9,11 was formulated as a topical cream and evaluated in patients with persistent facial erythema of rosacea. Oxymetazoline safety and efficacy were demonstrated in three phase 3 REVEAL trials, including two pivotal, double-blind registration trials and a long-term, open-label trial; findings of these studies led to FDA approval in January 2017 of oxymetazoline cream 1.0% for topical treatment of persistent facial erythema of rosacea in adults.12 We report the results of a phase 2 dose-ranging study designed to evaluate the safety and efficacy of 3 doses of oxymetazoline cream (0.5%, 1.0%, and 1.5%) administered once daily (QD) or twice daily (BID) for 28 consecutive days compared with vehicle for treatment of moderate to severe facial erythema of rosacea. 

METHODS

Study Design

This multicenter, randomized, double-blind, vehicle-controlled, parallel-group, phase 2 study (ClinicalTrials.gov identifier NCT01735201) was conducted at 15 centers in the United States from December
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