PT - JOURNAL ARTICLE AU - Alexa Kollmeier AU - Klaus Francke AU - Bin Chen AU - Paul J. Dunford AU - Andrew J. Greenspan AU - Yichuan Xia AU - Xie L. Xu AU - Bei Zhou AU - Robin L. Thurmond TI - The Histamine H<sub>4</sub> Receptor Antagonist, JNJ 39758979, Is Effective in Reducing Histamine-Induced Pruritus in a Randomized Clinical Study in Healthy Subjects AID - 10.1124/jpet.114.215749 DP - 2014 Jul 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 181--187 VI - 350 IP - 1 4099 - http://jpet.aspetjournals.org/content/350/1/181.short 4100 - http://jpet.aspetjournals.org/content/350/1/181.full SO - J Pharmacol Exp Ther2014 Jul 01; 350 AB - 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 &lt; 0.0001). Adverse eventss reported in &gt;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.