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)

详细信息    查看全文

• 作者：Lixin Zhang^&lowast ; ; Michelle Rainka^&lowast ; ; Roy Freeman^&dagger ; ; R. Norman Harden^&Dagger ; ; Christopher F. Bell^§ ; ; Chao Chen^§ ; ; Ole Graff^§ ; ; Kathleen Harding^§ ; ; Setrina Hunter^§ ; ; Sarah Kavanagh^§ ; ; Bart Laurijssens^¶ ; ; Caryl Schwartzbach^§ ; ; Samantha Warren^§ ; ; Carrie McClung^§ ; ; ^{carrie.l.mcclung@gsk.com}
• 关键词：Postherpetic neuralgia ; gabapentin ; gabapentin enacarbil ; neuropathic pain ; herpes zoster
• 刊名：The Journal of Pain
• 出版年：2013
• 出版时间：June, 2013
• 年：2013
• 卷：14
• 期：6
• 页码：590-603
• 全文大小：1144 K

文摘

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 ¡Ý4.0 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.

Perspective

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.