This randomized, double-blind, placebo-controlled, multicenter, 2-period crossover study (two 6-week treatment periods separated by a 2-week washout period) evaluated the efficacy and safety of pregabalin (150 to 300 mg/d) for treatment of pain and pain on walking in patients with painful diabetic peripheral neuropathy (DPN) who experienced pain while walking.
Co-primary efficacy endpoints were: (1) mean pain score (last 7 daily pain diary scores, 0 to 10 numeric rating scale at end of each treatment period) and (2) DPN pain on walking (0 to 10 numeric rating scale immediately after walking 50 feet [15.2 m] on flat surface). Secondary endpoints included other pain parameters, patient-reported sleep, health-related quality of life, and safety measures.
Two hundred three patients were treated (pregabalin, n=198; placebo, n=186), with no statistically significant treatment difference for pregabalin versus placebo in the co-primary efficacy endpoints, mean DPN pain (P=0.0656) and mean DPN pain on walking (P=0.412). A carryover effect was observed. Analysis of co-primary endpoints for period 1 showed significant treatment difference for DPN pain (P=0.034) and DPN pain on walking (P=0.001). Treatment with pregabalin resulted in significant improvements versus placebo on prespecified patient global impression of change (end of period 1; P=0.002), and sleep interference rating scale (end of period 2; P=0.011). Adverse events were more frequent with pregabalin than with placebo and caused discontinuation in 13 (6.6%) pregabalin patients versus 5 (2.7%) placebo patients.
Failure to meet the co-primary objectives may be related to carryover effect from period 1 to period 2, lower pregabalin dose (150 to 300 mg/d), and/or placebo response in painful DPN.
*Meridien Research, Tampa, FL
†Oregon Health & Science University, Portland, OR
‡Palm Beach Neurological Center, Palm Beach Gardens, FL
§Pfizer Ltd, Tadworth, Surrey, UK
∥Pfizer Inc., New York, NY
¶Pfizer Inc., Groton, CT
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Sponsored by Pfizer Inc. Medical writing support was provided by Vardit Dror, PhD, of Engage Scientific Solutions and funded by Pfizer Inc.
C.H. has conducted multiple clinical trials for Pfizer Inc., New York, NY, and other pharmaceutical sponsors. B.R.S. was a paid consultant to Pfizer, Boston Scientific, Marlborough, MA, and Xenoport, Santa Clara, CA. M.T. received research funding and speaker honoraria from Pfizer. C.B., C.L., B.P., L.P., J.M.S., R.B., and L.Y. are full-time employees of Pfizer and declare stock options from Pfizer Inc., New York, NY.
Reprints: Lorraine Yurkewicz, PhD, Clinical Sciences, Pfizer Primary Care, 558 Eastern Point Rd, Groton, CT 06340 (e-mail: email@example.com).
Received June 20, 2014
Received in revised form January 12, 2015
Accepted December 8, 2014