title: A randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of gabapentin enacarbil in subjects with neuropathic pain associated with postherpetic neuralgia (PXN110748).
abstract: Gabapentin enacarbil (GEn) is an actively transported prodrug of gabapentin that provides sustained, dose-proportional exposure to gabapentin. This randomized, double-blind, parallel-group, placebo-controlled study evaluated the safety and efficacy of 3 different maintenance doses of oral GEn in subjects with postherpetic neuralgia. Adults with a 24-hour average pain intensity score of ≥4.0 received GEn 1,200 mg, 2,400 mg, 3,600 mg, or placebo for 14 weeks (including a 1-week up-titration, 12-week maintenance, and 1-week taper). The primary endpoint was change from baseline to end of maintenance treatment in mean 24-hour average pain intensity score. The intent-to-treat population consisted of 371 subjects (GEn 1,200 mg = 107, 2,400 mg = 82, 3,600 mg = 87, placebo = 95). With regard to the primary endpoint, all 3 GEn treatment groups demonstrated a statistically significant difference relative to placebo. The adjusted mean change from baseline for the treatment groups ranged from -2.36 to -2.72 versus -1.66 for the placebo group. Exposure-response modeling suggested an ED50 around 1,200 mg/day, which was consistent with historical findings reported for gabapentin. The most commonly reported adverse events were dizziness and somnolence. All studied doses of GEn significantly improved pain associated with postherpetic neuralgia as compared to placebo and were well tolerated.
  
  
  CONCLUSIONS
  GEn provides clinically important pain relief with doses from 1,200 mg to 3,600 mg and is generally well tolerated and efficacious. As an actively transported prodrug of gabapentin, it provides dose-proportional and extended exposure to gabapentin.
authors.affiliation: Dent Neurologic Institute, Amherst, New York, USA.
authors.forename: Lixin
authors.initials: L
authors.lastname: Zhang
authors.forename: Michelle
authors.initials: M
authors.lastname: Rainka
authors.forename: Roy
authors.initials: R
authors.lastname: Freeman
authors.forename: R Norman
authors.initials: RN
authors.lastname: Harden
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Bell
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.forename: Ole
authors.initials: O
authors.lastname: Graff
authors.forename: Kathleen
authors.initials: K
authors.lastname: Harding
authors.forename: Setrina
authors.initials: S
authors.lastname: Hunter
authors.forename: Sarah
authors.initials: S
authors.lastname: Kavanagh
authors.forename: Bart
authors.initials: B
authors.lastname: Laurijssens
authors.forename: Caryl
authors.initials: C
authors.lastname: Schwartzbach
authors.forename: Samantha
authors.initials: S
authors.lastname: Warren
authors.forename: Carrie
authors.initials: C
authors.lastname: McClung
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000777:Anesthetics / Q000627:therapeutic use*; D002219:Carbamates / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D051474:Neuralgia, Postherpetic / Q000175:diagnosis* / Q000188:drug therapy*; D010147:Pain Measurement; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: C493250:1-(((alpha-isobutanoyloxyethoxy)carbonyl)aminomethyl)-1-cyclohexaneacetic acid; D000777:Anesthetics; D002219:Carbamates; D005680:gamma-Aminobutyric Acid