Efficacy and Safety of Once-Daily Controlled-Release Pregabalin for the Treatment of Patients With Postherpetic Neuralgia: A Double-Blind, Enriched Enrollment Randomized Withdrawal, Placebo-Controlled Trial

Clin J Pain. 2017 Jul;33(7):569-578. doi: 10.1097/AJP.0000000000000445.

Abstract

Objectives: To assess efficacy and safety of once-daily controlled-release (CR) formulation of pregabalin in patients with postherpetic neuralgia.

Methods: An enriched enrollment, randomized withdrawal trial, with 6-week single-blind pregabalin treatment phase and 13-week double-blind phase, where patients with ≥50% decrease in mean pain score at single-blind end point from baseline were randomized (1:1) to pregabalin CR (82.5 to 660 mg/d) or placebo. Primary efficacy outcome was time to loss of therapeutic response (LTR) (<30% decrease in weekly mean pain score from single-blind baseline or discontinuation due to adverse event or lack of efficacy). Secondary efficacy outcomes included change in weekly mean pain score (1-wk recall period) at double-blind end point.

Results: In total, 801 patients were randomized and treated in the single-blind phase, and 413 in the double-blind phase (208, pregabalin CR; 205, placebo). Pregabalin CR significantly increased time to LTR versus placebo (Kaplan-Meier analysis) with significantly fewer LTR events with pregabalin CR than with placebo (29 [13.9%] vs. 63 [30.7%]; P<0.0001). Median time to LTR was not estimable. Pregabalin CR significantly improved weekly mean pain score versus placebo: LS mean difference (95% CI) of -1.11 (-1.47, -0.75) and -1.00 (-1.34, -0.65) (P<0.0001) from single-blind baseline and double-blind baseline, respectively. Most commonly reported adverse events in the single-blind phase were dizziness, somnolence, and peripheral edema. Pregabalin CR was well tolerated.

Discussion: Time to LTR was significantly longer with pregabalin CR than with placebo. Safety profile of pregabalin CR was comparable to that reported for the immediate-release formulation in patients with postherpetic neuralgia.

Trial registration: ClinicalTrials.gov NCT01270828.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Analgesics / administration & dosage*
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • International Cooperation
  • Male
  • Middle Aged
  • Neuralgia, Postherpetic / drug therapy*
  • Pain Measurement
  • Patient Compliance
  • Pregabalin / administration & dosage*
  • Psychiatric Status Rating Scales
  • Single-Blind Method
  • Treatment Outcome*
  • Young Adult

Substances

  • Analgesics
  • Pregabalin

Associated data

  • ClinicalTrials.gov/NCT01270828