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.

摘要

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 is less than or equal to 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.