The H4 receptor antagonist, JNJ 39758979, is effective in reducing histamine-induced pruritus in a randomized clinical study in healthy subjects

J Pharmacol Exp Ther jpet.114.215749; published ahead of print May 9, 2014, doi:10.1124/jpet.114.215749

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1. Alexa Kollmeier1, 
2. Klaus Francke2, 
3. Bin Chen1, 
4. Paul J Dunford1,
5. Andrew J Greenspan1, 
6. Yichan Xia1, 
7. Xie L Xu1, 
8. Bei Zhou1, and
9. Robin Thurmond3,*

+Author Affiliations

1. ¹ Janssen Research & Development, LLC;
2. ² Parexel International;
3. ³ Janssen Research & Development, L.L.C.

1. ↵* Corresponding author; email: rthurmon@its.jnj.com

Abstract

The histamine H₄ receptor (H₄R) is a promising target for the treatment of pruritus. A clinical study was conducted to evaluate safety and efficacy of the H₄R antagonist, JNJ 39758979, on histamine-induced pruritus in healthy subjects. A single oral dose of 600mg JNJ 39758979, 10mg cetirizine, or placebo was administered in a randomized, 3-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 h post-dose on day 1 of each treatment period. The primary efficacy endpoint was area under the curve (AUC) of pruritus score 0-10 minutes post-histamine challenge. Secondary efficacy endpoints included wheal and flare areas assessed 10 minutes post-histamine challenge. Safety was assessed for all subjects. Twenty-four subjects were enrolled and 23 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 AUC of pruritus score was significant for JNJ 39758979 at 2 h (p=0.0248) and 6 h (p=0.0060), and for cetirizine at 6 h (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 h (p-0.0001). Adverse events 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.

This Article

1. Published online before print May 9, 2014, doi:10.1124/jpet.114.215749JPET May 9, 2014jpet.114.215749

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