title: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study of the T-Type Calcium Channel Blocker ABT-639 in an Intradermal Capsaicin Experimental Pain Model in Healthy Adults.
abstract: This randomized, double-blind, placebo-controlled, crossover trial evaluated the pharmacodynamic effects of a single 100-mg dose of ABT-639, a peripherally active, selective T-type Cav3.2 channel blocker, with the intradermal capsaicin pain model using pregabalin 300 mg as a positive control.
  
  
  
  Healthy adult males (aged 21 to 55 years) were randomly assigned to receive single oral doses of ABT-639, pregabalin, and placebo.
  
  
  
  Serial measurements for area (cm2) of hyperalgesia, allodynia, and flare response were performed over a 20-minute period after each capsaicin injection at 1 and 4 hours post-dose. Capsaicin injections were administered in different arms as determined by random assignment. Serial measurements for spontaneous pain and elicited pain were performed over a 60-minute period at 1 and 4 hours post-dose using a 100-mm visual analog scale. Standard safety evaluations were performed.
  
  
  
  Nineteen participants were randomized and included in the analysis. No significant differences were observed between ABT-639 and placebo in spontaneous pain, elicited pain, and areas of allodynia, hyperalgesia, and flare after intradermal capsaicin injection at 1 and 4 hours post-dose. In contrast, pregabalin demonstrated significant reductions in spontaneous pain at 1 and 4 hours post-dose, and elicited pain and areas of allodynia and hyperalgesia at 4 hours post-dose compared with placebo. ABT-639 demonstrated acceptable safety and tolerability; somnolence and euphoric mood were the most commonly reported adverse events.
  
  
  
  These data indicate that a single 100-mg dose of ABT-639 had no effect on experimental pain induced by intradermal capsaicin injection.
authors.affiliation: *Division of Pain Medicine, Department of Anesthesiology, University of California San Diego, La Jolla, California, USA mswallace@ucsd.edu.
authors.forename: Mark
authors.initials: M
authors.lastname: Wallace
authors.affiliation: AbbVie Inc., North Chicago, Illinois, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Duan
authors.affiliation: AbbVie Inc., North Chicago, Illinois, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: AbbVie Inc., North Chicago, Illinois, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Locke
authors.affiliation: AbbVie Inc., North Chicago, Illinois, USA.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Nothaft
mesh_terms: D000328:Adult; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D020747:Calcium Channels, T-Type / Q000378:metabolism*; D002211:Capsaicin / Q000008:administration & dosage / Q000009:adverse effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006574:Heterocyclic Compounds, 2-Ring / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007271:Injections, Intradermal; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods*; D000069583:Pregabalin / Q000494:pharmacology / Q000627:therapeutic use; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D055815:Young Adult; D000096926:Benzenesulfonamides
chemical_list: D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D002211:Capsaicin; D006574:Heterocyclic Compounds, 2-Ring; D000069583:Pregabalin; D013449:Sulfonamides; C000589982:4-chloro-2-fluoro-N-(2-fluorophenyl)-5-(hexahydropyrrolo(1,2-a)pyrazin-2(1H)-ylcarbonyl)benzenesulfonamide; D000096926:Benzenesulfonamides
keywords: ABT-639; Intradermal Capsaicin; T-type Calcium Channels