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.

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.