The
histamine H4 receptor (H4R) is a promising target for the treatment of
pruritus. A clinical study was conducted to evaluate the safety and efficacy of the H4R antagonist,
JNJ 39758979 [(R)-4-(3-amino-pyrrolidin-1-yl)-6-isopropyl-pyrimidin-2-ylamine], on
histamine-induced
pruritus in healthy subjects. A single oral dose of 600 mg
JNJ 39758979, 10 mg
cetirizine, or placebo was administered in a randomized, three-period, double-blind, crossover study. Treatment periods were separated by 22-day washout periods. A
histamine challenge was administered on day -1 and at 2 and 6 hours postdose on day 1 of each treatment period. The primary efficacy endpoint was the area under the curve (AUC) of
pruritus score 0-10 minutes after the
histamine challenge. Secondary efficacy endpoints included wheal and flare areas assessed 10 minutes after the
histamine challenge. Safety was assessed for all subjects. Of the 24 enrolled subjects, 23 individuals completed the study. One subject withdrew after completing two treatment periods. Due to a carryover effect of
JNJ 39758979, only treatment period 1 was used for
pruritus-related evaluations. Compared with placebo, the reduction of the AUC of
pruritus score was significant for
JNJ 39758979 at 2 hours (P = 0.0248) and 6 hours (P = 0.0060), and for
cetirizine at 6 hours (P = 0.0417). In all treatment periods,
JNJ 39758979 did not demonstrate a significant decrease in wheal or flare at either time point, although a significant reduction was achieved with
cetirizine at 2 and 6 hours (P < 0.0001). Adverse eventss reported in >1 patient with
JNJ 39758979 were
headache (9%) and
nausea (13%). In conclusion,
JNJ 39758979 was effective in inhibiting
histamine-induced
pruritus in healthy subjects.