Objectives: This study used a randomized withdrawal design to evaluate the efficacy of pregabalin versus placebo for pain relief in patients with painful diabetic peripheral neuropathy inadequately treated by other therapies.
Methods: A total of 665 patients received pregabalin in a 6-week single-blind phase. Two hundred ninety-four patients who achieved a ≥30% pain response were randomized to receive pregabalin or placebo in a double-blind phase for a further 13 weeks. The primary endpoint was the change in mean pain score from single-blind baseline to double-blind endpoint for pregabalin versus placebo (last observation carried forward [LOCF]). Secondary endpoints included a baseline observation carried forward (BOCF) analysis of mean pain score; time to loss of pain response; and other assessments of pain, sleep, function, and quality of life (QOL).
Results: Pregabalin numerically improved all measures assessed during the single-blind phase. At the end of the double-blind withdrawal phase, there was no significant difference in the primary endpoint of mean pain score (LOCF) between pregabalin and placebo (least squares mean difference, −0.32), although there was a significant difference in the BOCF analysis (least squares mean difference, −0.51). Pregabalin was associated with a significantly longer time to loss of pain response versus placebo during double-blind treatment, and some aspects of sleep and QOL also showed significant improvements with pregabalin.
Discussion: This is the first reported placebo-controlled trial of pregabalin in patients with inadequately treated painful diabetic peripheral neuropathy. Although the primary endpoint was not met, pregabalin was associated with clinically relevant improvements versus placebo in this difficult-to-treat population.
*Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX
†Meridien Research, Tampa, FL
§Pfizer Inc, New York, NY
‡Department of Clinical Neurosciences, The University of Calgary, Calgary, AB, Canada
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Supported by Pfizer Inc. Medical writing support was provided by Lorna Forse, PhD, of UBC Scientific Solutions and funded by Pfizer Inc. P.R. has received research support, payable to the University of Texas Southwestern Medical Center, from Andromeda Biotech Ltd., Yavne, Israel, AstraZeneca Pharmaceuticals LP, Wilmington, DE, Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT, Calibra Medical Inc., Redwood City, CA, Halozyme Inc., San Diego, CA, Hoffmann-La Roche Inc., Nutley, NJ, Eli Lilly & Company USA LLC, Indianapolis, IN, Osiris Therapeutics Inc., Columbia, MD, Pfizer Inc, New York, NY, and Reata Pharmaceuticals Inc., Irving, TX; is an advisor for Amgen Inc, Thousands Oaks, CA and AstraZeneca Pharmaceuticals LP, Wilmington, DE and is on the speaker’s bureau for Novo Nordisk Inc., Princeton, NJ. C.H. has conducted multiple clinical trials for Pfizer Inc, New York, NY and other pharmaceutical sponsors. C.T. has received clinical and preclinical research funding, as well as honoraria for medical education seminars from Pfizer Inc, New York, NY. M.J.A., M.M., R.J.S., and L.P. are full-time employees of Pfizer Inc and hold stock options with Pfizer Inc.
Reprints: Philip Raskin, MD, Department of Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-8858 (e-mail: email@example.com).
Received October 26, 2012
Accepted May 21, 2013