A Randomized, Double-Blind, Vehicle-Controlled Crossover Study to Determine the Anti-Pruritic Efficacy, Safety and Local Dermal Tolerability of a Topical Formulation (SRD174 Cream) of the Long-Acting Opiod Antagonist Nalmefene in Subjects With Atopic Dermatitis
August 2011 | Volume 10 | Issue 8 | Original Article | 853 | Copyright © August 2011
Jo Lynne Herzog MD,a James A.Solomon MD PhD,b Zoe Draelos MD,c Alan Fleischer Jr. MD,d Dow Stough MD,e David I.Wolf MD,f William Abramovits MD,g William Werschler MD,h Emma Green BSc,i Maeve Duffy PhD,i Alan Rothaul PhD,i Robert Tansley MBBSi
aRadiant Research Inc., Birmingham, AL bAdvanced Dermatology & Cosmetic Surgery, Ormond Beach, FL cDermatology Consulting Services, High Point, NC dWake Forest University School of Medicine, NC eBurke Pharmaceutical Research, Hot Springs, AZ fDermatology Specialists Inc., Oceanside, CA gBaylor University Medical Center, Dallas, TX hPremier Clinical Research, Spokane, WA iSerentis Ltd., Cambridge, UKiSerentis Ltd., Cambridge, UK
Objective: To investigate the efficacy, safety and tolerability of topical nalmefene (SRD174), a long acting opioid antagonist for the management of pruritus associated with atopic dermatitis (AD).
Design: Double-blind, vehicle-controlled, randomized, cross-over trial.
Setting: Eleven dermatology outpatient clinics in the U.S.
Patients: Sixty-two out of 136 screened adult subjects with confirmed AD affecting ≤20% of body surface area and with moderate-to-severe pruritus.
Interventions: SRD174 cream or matching vehicle cream applied as required during two 7-day periods separated by a wash-out period.
Main Outcome Measure(s): The primary efficacy variable was the period mean of the sum of pruritus intensity difference (SPID) from 0 to 4 hours (SPID0-4) where pruritus was measured on a 0-100 scale Visual Analog Scale (VAS) at seven pre-specified time-points following study drug application. A range of secondary efficacy, safety and tolerance endpoints were included.
Results: The LS means for the SPID0-4 (±SD) for SRD174 cream and Vehicle were 210.7 (20.4) and 212.1 (20.2), respectively (Difference = -1.3 (95% CI: -25.9, 23.3). None of the secondary efficacy endpoints tested demonstrated a statistically significant or clinically important difference between the test product and the vehicle. Overall, the SRD174 cream was well tolerated although there was a higher incidence of AEs when subjects took SRD174 cream (22, 36.7 percent of subjects) compared with when they were taking vehicle (14, 23.3 percent of subjects).
Conclusions: SRD174 cream did not demonstrate efficacy in the treatment of pruritus associated with atopic dermatitis raising questions on the role of peripheral opioid receptors as a target for the treatment of pruritus in this population. NCT00838708
J Drugs Dermatol. 2011;10(8):853-860.