To assess efficacy and safety of once-daily controlled-release (CR) formulation of pregabalin in patients with postherpetic neuralgia.
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.
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.
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.
*Meridien Research, Tampa
†JEM Research Institute, Atlantis, FL
‡Michigan Headache and Neurological Institute, Ann Arbor, MI
§Pfizer, New York, NY
∥Pfizer, Groton, CT
Trial registration number: NCT01270828.
Supported by Pfizer. Medical writing support was provided by Vatsala Malik, PhD, of Engage Scientific Solutions and was funded by Pfizer, NY, NY. L.S., J.D., R.Y., M.L.C., and J.M.S. are full-time employees of Pfizer and hold stock options in Pfizer. The other authors declare no conflict of interest.
Reprints: James Weintraub, DO, Michigan Headache and Neurological Institute, 3120 Professional Dr, Ann Arbor, MI 48104 (e-mail: email@example.com).
Received March 8, 2016
Received in revised form December 6, 2016
Accepted October 1, 2016