title: A randomized, double-blind, placebo-controlled trial of a chemokine receptor 2 (CCR2) antagonist in posttraumatic neuralgia.
abstract: 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 28days' oral administration of 20mg AZD2423, 150mg AZD2423 or placebo. The primary efficacy variable was the change of average pain score from 5days at baseline to the last 5days 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 20mg -1.54; AZD2423 150mg -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 150mg 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 150mg) 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.
authors.affiliation: AstraZeneca R&D Södertälje, SE-151 85 Södertälje, Sweden INSERM U987, Centre d'Evaluation et de Traitement de la Douleur, Hôpital Ambroise Paré, Boulogne-Billancourt F-92100, France Université Versailles-Saint-Quentin, Versailles F-78035, France Department of Neurology, Aarhus University Hospital, Aalborg Sygehus DK-9100, Denmark MAC UK Neuroscience, 4 Lumsdale Road, Cobra Court, Trafford Park, Manchester M32 0UT, UK Department of Palliative Care and Palliative Medicine, Medical University of Silesia, 40-752 Katowice, Poland Department of Neurology, I.M. Sechenov Moscow Medical Academy, Trubeckaya Street 8, Building 2, 119992 Moscow, Russian Federation.
authors.forename: Jarkko
authors.initials: J
authors.lastname: Kalliomäki
authors.forename: Nadine
authors.initials: N
authors.lastname: Attal
authors.forename: Bror
authors.initials: B
authors.lastname: Jonzon
authors.forename: Flemming W
authors.initials: FW
authors.lastname: Bach
authors.forename: Karin
authors.initials: K
authors.lastname: Huizar
authors.forename: Stuart
authors.initials: S
authors.lastname: Ratcliffe
authors.forename: Britta
authors.initials: B
authors.lastname: Eriksson
authors.forename: Marcin
authors.initials: M
authors.lastname: Janecki
authors.forename: Andrei
authors.initials: A
authors.lastname: Danilov
authors.forename: Didier
authors.initials: D
authors.lastname: Bouhassira
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005060:Europe; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy / Q000453:epidemiology; D007052:Ibuprofen / Q000627:therapeutic use; D057194:Intention to Treat Analysis; D008297:Male; D008875:Middle Aged; D009437:Neuralgia / Q000188:drug therapy* / Q000209:etiology*; D010147:Pain Measurement / Q000187:drug effects; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors*; D018401:Sample Size; D016896:Treatment Outcome; D014947:Wounds and Injuries / Q000150:complications*; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D054390:Receptors, CCR2; D007052:Ibuprofen