Results from clinical trials of a selective ionotropic glutamate receptor 5 (iGluR5) antagonist, LY5454694 tosylate, in 2 chronic pain conditions.

Abstract

This article reports results of 2 studies investigating LY545694 in pain due to osteoarthritis (OA) of the knee and diabetic peripheral neuropathic pain (DPNP). Study I randomized patients to either of 2 doses of LY545694 or to placebo, and study II randomized patients to either of 3 doses of LY545694, to pregabalin, or to placebo. No significant differences between LY545694 groups and placebo were observed on the primary (average pain severity) or secondary efficacy measures in either study. Notably, study I lacked an active control, and, in study II, pregabalin, did not separate from placebo. Treatment-emergent nausea, vomiting, and dizziness were significantly more frequent in the LY545694 groups in both trials (P⩽.05), and significantly more LY545694-treated patients discontinued because of adverse events (P<.001). Steady-state concentrations of LY545694 were comparable in patients in both studies but were lower than exposures required for efficacy in animal models of pain behavior. Because the active control did not separate from placebo in the DPNP study, the study was potentially failed, rather than negative. Without an active control, it is unknown whether the OA study was negative or failed. Consequently, efficacy of selective ionotropic glutamate receptor antagonism in chronic pain conditions may warrant further investigation. Future trials should consider different pain conditions, contain a positive control with larger patient numbers per arm, and be conducted within a single region.

• Authors: Amy S Chappell, Smriti Iyengar, Evelyn D Lobo, William R Prucka
• Journal: Pain (Pain) Vol. 155 Issue 6 Pg. 1140-1149 (Jun 2014) ISSN: 1872-6623 [Electronic] United States
• PMID: 24631589 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Chemical References

• Excitatory Amino Acid Antagonists
• Gluk1 kainate receptor
• Receptors, Kainic Acid

Topics

• Aged
• Chronic Pain (diagnosis, drug therapy)
• Double-Blind Method
• Excitatory Amino Acid Antagonists (pharmacology, therapeutic use)
• Female
• Humans
• Male
• Middle Aged
• Pain Measurement (drug effects, methods)
• Receptors, Kainic Acid (antagonists & inhibitors, physiology)
• Treatment Outcome