Efficacy and safety of PAC-14028 cream - a novel, topical, nonsteroidal, selective TRPV1 antagonist in patients with mild-to-moderate atopic dermatitis: a phase IIb randomized trial

Background Transient receptor potential vanilloid subfamily, member 1 (TRPV1) may play an important role in pruritus and inflammation induction in atopic dermatitis (AD). The treatment effect of TRPV1 antagonist via topical application in patients with AD remains unknown. Objectives To assess the clinical efficacy and safety of PAC-14028, a TRPV1 antagonist, via topical application in patients with AD. Methods In this 8-week, phase IIb, randomized, double-blind, multicentre, vehicle-controlled study, patients with mild-to-moderate AD were randomized to receive PAC-14028 cream 0 center dot 1%, 0 center dot 3%, 1 center dot 0% or vehicle cream twice daily. The primary efficacy end point was the Investigator's Global Assessment (IGA) success rate defined as the percentage of patients with an IGA score of 0 or 1 at week 8. The secondary efficacy end points included the severity Scoring of Atopic Dermatitis (SCORAD) index and Eczema Area and Severity Index (EASI) 75/90. Results A total of 194 patients were enrolled. IGA success rates at week 8 were 14 center dot 58% for vehicle cream, 42 center dot 55% for PAC-14028 cream 0 center dot 1% (P = 0 center dot 0025 vs. vehicle), 38 center dot 30% for PAC-14028 cream 0 center dot 3% (P = 0 center dot 0087 vs. vehicle) and 57 center dot 45% for PAC-14028 cream 1 center dot 0% (P < 0 center dot 001 vs. vehicle). In particular, statistically significant differences were found between the vehicle and treatment groups in the IGA success rates with two-grade improvement. The SCORAD index, EASI 75/90, sleep disturbance score and pruritus visual analogue scale showed a trend towards improvement. No significant safety issues were reported. Conclusions PAC-14028 cream may be an effective and safe treatment modality for the treatment of patients with mild-to-moderate AD.