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.
Trial registration: ClinicalTrials.gov NCT01057693.