A randomized, double-blind, placebo-controlled trial of a chemokine receptor 2 (CCR2) antagonist in posttraumatic neuralgia

作者：Kalliomaki Jarkko^*; Attal Nadine; Jonzon Bror; Bach Flemming W; Huizar Karin; Ratcliffe Stuart; Eriksson Britta; Janecki Marcin; Danilov Andrei; Bouhassira Didier

来源：Pain, 2013, 154(5): 761-767.

DOI：10.1016/j.pain.2013.02.003

• CCR2
• CCR2 antagonist
• Chemokines
• Neuropathic pain
• Posttraumatic neuralgia
• Randomized controlled trial

We evaluated the analgesic efficacy, safety and tolerability of a novel chemokine receptor 2 (CCR2) antagonist, AZD2423, in posttraumatic neuralgia. This was a double-blind, randomized, parallel-group, multicentre study. One hundred thirty-three patients with posttraumatic neuralgia were equally randomized to 28 days%26apos; oral administration of 20 mg AZD2423, 150 mg AZD2423 or placebo. The primary efficacy variable was the change of average pain score from 5 days at baseline to the last 5 days of treatment, measured by a numerical rating scale (NRS, 0-10). The secondary efficacy measures included NRS worst pain score, patient global impression of change, pain interference on sleep and activity, and Neuropathic Pain Symptom Inventory (NPSI). The change of the NRS average pain score was not significantly different between treatment groups (AZD2423 20 mg -1.54; AZD2423 150 mg -1.53; placebo -1.44). There were trends towards larger reduction of NPSI total score and NPSI subscores for paroxysmal pain and paresthesia/dysesthesia by AZD2423 150 mg compared to placebo. No other secondary efficacy variables differed between treatment groups. The frequency and type of adverse events for AZD2423 were similar to placebo. Increased plasma levels of chemokine ligand 2 and reduced mean levels of monocytes (-30% by AZD2423 150 mg) suggested that the administrated doses of AZD2423 had interacted with the CCR2 target. The CCR2 antagonist AZD2423 demonstrated no efficacy on NRS average pain scores and most of the secondary pain variables. The NPSI data suggested possible effects on certain sensory components of pain. There were no major safety or tolerability concerns.

• 出版日期2013-5