Safety and Efficacy of a Topical Sodium Channel Inhibitor (TV-45070) in Patients with Post Herpetic Neuralgia (PHN): A Randomized, Controlled, Proof-of-Concept, Crossover Study, With a Subgroup Analysis of the Nav1.7 R1150W Genotype
Price N.,Xenon Pharmaceuticals Inc. Burnaby
Clinical Journal of Pain | Year: 2016
OBJECTIVES:: To evaluate the safety and efficacy of TV-45070 ointment, as a treatment for PHN, and to explore the response in patients with the Nav1.7 R1150W gain-of-function polymorphism. METHODS:: This was a randomized, placebo-controlled, 2-period, 2-treatment crossover trial. Patients with PHN with moderate or greater pain received TV-45070 and Placebo ointments, each applied twice daily for 3 weeks. The primary efficacy measure was the difference in change in mean daily pain score from baseline compared to the last week of placebo and active treatment. Secondary endpoints included responder rate analyses and a further exploratory analysis of response in carriers of the Nav1.7 R1150W polymorphism was conducted. RESULTS:: Seventy patients were enrolled and 54 completed the study. TV-45070 was safe and well tolerated. No statistical difference was observed between treatments for the primary endpoint. However, the proportion of patients with ≥50% reduction in mean pain scores at Week 3 was greater on TV-45070 than on placebo (26.8% vs. 10.7%, P=0.0039). Similarly, a greater proportion of patients on TV-45070 had a ≥30% reduction in mean pain scores at Week 3 (39.3% on TV-45070 vs. 23.2% on placebo, P=0.0784). Of note, 63% of patients with the R1150W polymorphism vs. 35% of wildtype carriers had a ≥30% reduction in mean pain score on TV-45070 at Week 3 (no inferential analysis performed). CONCLUSIONS:: The 50% responder analysis suggests a subpopulation may exist with a more marked analgesic response to TV-45070.The trend toward a larger proportion of responders within Nav1.7 R1150W carriers warrants further investigation. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.