Efficacy and tolerability of pregabalin using a flexible, optimized dose schedule in Korean patients with peripheral neuropathic pain: a 10-week, randomized, double-blind, placebo-controlled, multicenter study.
Author(s): Moon DE, Lee DI, Lee SC, Song SO, Yoon DM, Yoon MH, Kim HK, Lee YW, Kim C, Lee PB
Affiliation(s): Department of Anesthesiology and Pain Medicine, School of Medicine, Catholic University of Korea, Seoul, Korea.
Publication date & source: 2010-12, Clin Ther., 32(14):2370-85.
Publication type: Clinical Trial, Phase III; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
BACKGROUND: Clinical trials from various countries have reported the efficacy of pregabalin for reducing peripheral neuropathic pain. OBJECTIVE: This study assessed the efficacy and tolerability of pregabalin in Korean patients with neuropathic pain. METHODS: This was a Phase III, 10-week, randomized, double-blind, placebo-controlled, multicenter study. Patients aged >/= 18 years with neuropathic pain (diabetic peripheral neuropathy, postherpetic neuralgia, or posttraumatic neuropathic pain) were enrolled and randomly assigned (2:1 ratio) to pregabalin (150-600 mg/d) or matching placebo. Randomization was performed using a proprietary telerandomization system. The primary end point was the difference in week 8 least squares (LS) mean Daily Pain Rating Scale (DPRS) score (rated once daily from 0 ["no pain"] to 10 ["worst possible pain"]) between pregabalin and placebo, calculated using the average of the last 7 available DPRS scores. Secondary efficacy measures included the following: the proportion of responders whose DPRS scores were reduced by >/= 30% or >/= 50% versus baseline, the Daily Sleep Interference Scale (DSIS; 11-point scale, scored daily), the Euro Quality of Life assessment (EQ-5D; 2 items scored separately), the Medical Outcomes Study (MOS) Sleep Scale (12 items each scored separately), the Hospital Anxiety and Depression Scale (HADS; 2 items scored from 0 to 21), the Patient Global Impression of Change (PGIC) and the Clinical Global Impression of Change (CGIC; each scored on a 7-point scale), and tolerability assessments. Adverse events and vital signs were monitored throughout the study with laboratory measurements, physical examinations, neurologic examinations, and 12-lead ECG tests. Data were analyzed using ANCOVA or Cochran-Mantel-Haenszel test, and P < 0.05 was considered statistically significant. RESULTS: The treatment groups (n = 162 pregabalin; n = 78 placebo) were well matched at baseline (pregabalin: 51.2% [83/162] female; mean [SD] age, 59.7 [10.8] years; weight, 63.6 [9.3] kg; placebo: 59.0% [46/78] female; mean age, 61.3 [12.9] years; weight, 62.0 [9.5] kg). All patients were Korean. The mean doses at end point were 480 mg/d for pregabalin and 513 mg/d for the placebo equivalent. Most patients received concomitant drug treatments during the study: 79.6% (129/162) in the pregabalin group and 92.3% (72/78) in the placebo group. The mean DPRS score at end point was significantly lower in the pregabalin group than in the placebo group (LS mean difference, -0.50; 95% CI, -1.00 to 0.00; P = 0.049). In total, 26.1% (42/161) of pregabalin-treated patients reported >/= 50% improvement in mean DPRS scores from baseline, compared with 14.3% (11/77) for placebo (P = 0.041 between groups). The LS mean change in the DSIS from baseline to end point favored pregabalin (-0.51; 95% CI, -0.96 to -0.07; P = 0.024). Significant improvements were also recorded for overall MOS sleep interference score (difference in LS means, -0.65; P = 0.018) and HADS anxiety subscale score (-0.85; P = 0.038). Other secondary assessments (eg, EQ-5D, HADS depression subscale, PGIC, and CGIC) did not reach significance. A higher proportion of patients reported treatment-related adverse events with pregabalin (43.8% [71/162]) than with placebo (29.5% [23/78]). Dizziness (21.0% [34/162]), somnolence (13.6% [22/162]), face edema (6.2% [10/162]), peripheral edema (6.2% [10/162]), and weight gain (5.6% [9/162]) were the most commonly reported adverse events in the pregabalin group. CONCLUSION: Flexible-dose pregabalin (150-600 mg/d for 8 weeks) was associated with a significant, although modest, reduction in mean DPRS score; an improvement in anxiety and subjective sleep; and generally good tolerability compared with placebo in these Korean patients with neuropathic pain due to diabetic peripheral neuropathy, postherpetic neuralgia, or posttraumatic neuropathic pain. Copyright (c) 2010. Published by EM Inc USA.