title: Safety and Efficacy of a Topical Sodium Channel Inhibitor (TV-45070) in Patients With Postherpetic Neuralgia (PHN): A Randomized, Controlled, Proof-of-Concept, Crossover Study, With a Subgroup Analysis of the Nav1.7 R1150W Genotype.
abstract: The objective was to evaluate the safety and efficacy of TV-45070 ointment, as a treatment for postherpetic neuralgia, and to explore the response in patients with the Nav1.7 R1150W gain-of-function polymorphism.
  
  
  
  This was a randomized, placebo-controlled, 2-period, 2-treatment crossover trial. Patients with postherpetic neuralgia 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 with 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.
  
  
  
  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 versus 35% of wild-type carriers had a ≥30% reduction in mean pain score on TV-45070 at week 3 (no inferential analysis performed).
  
  
  
  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.
authors.affiliation: *Xenon Pharmaceuticals Inc., Burnaby §Division of General Internal Medicine, UBC, BC, Canada †Medpace Inc., Cincinnati, OH ‡Teva Pharmaceuticals Ltd, Frazer, Philadelphia, PA.
authors.forename: Nicola
authors.initials: N
authors.lastname: Price
authors.forename: Rostam
authors.initials: R
authors.lastname: Namdari
authors.forename: Judith
authors.initials: J
authors.lastname: Neville
authors.forename: Katie J W
authors.initials: KJ
authors.lastname: Proctor
authors.forename: Samer
authors.initials: S
authors.lastname: Kaber
authors.forename: Jeffery
authors.initials: J
authors.lastname: Vest
authors.forename: Michael
authors.initials: M
authors.lastname: Fetell
authors.forename: Richard
authors.initials: R
authors.lastname: Malamut
authors.forename: Robin P
authors.initials: RP
authors.lastname: Sherrington
authors.forename: Simon N
authors.initials: SN
authors.lastname: Pimstone
authors.forename: Yigal P
authors.initials: YP
authors.lastname: Goldberg
mesh_terms: D000287:Administration, Topical; D018592:Cross-Over Studies; D005260:Female; D005838:Genotype; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D062556:NAV1.7 Voltage-Gated Sodium Channel / Q000235:genetics*; D051474:Neuralgia, Postherpetic / Q000188:drug therapy* / Q000235:genetics*; D000075082:Proof of Concept Study; D026941:Sodium Channel Blockers / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D013141:Spiro Compounds / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D007211:Indoles; D062556:NAV1.7 Voltage-Gated Sodium Channel; C486866:SCN9A protein, human; D026941:Sodium Channel Blockers; D013141:Spiro Compounds; C000625639:TV-45070