Painful peripheral neuropathy remains a significant problem for many HIV/AIDS patients and there are few palliative or otherwise helpful therapies for this serious adverse event that may be associated with antiretroviral drug treatment, HIV infection itself, or both.

Pregabalin, an anti-epileptic drug, has previously demonstrated efficacy in several neuropathic pain syndromes. The FDA has approved Pfizer's pregabalin (Lyrica) for the treatment of fibromyalgia.

At the XVII International AIDS Conference last week in Mexico City, David Simpson of the Mount Sinai Medical Center in New York City presented results from the first trial to evaluate the efficacy, safety, and tolerability of pregabalin as a treatment for pain associated with HIV sensory neuropathy.

The central nervous system is comprised of the brain and spinal cord. The peripheral nervous system includes all peripheral nerves.

This randomized, double-blind, placebo-controlled, multicenter trial included 302 participants, 151 allocated to receive pregabalin and 151 to receive placebo. At baseline, the mean pain score was about 6.93 for the pregabalin arm and 6.72 for the placebo arm.

There were 4 phases: 1-2 week screening, 2-week double-blind dose-adjustment (150-600 mg/day taken twice-daily), 12-week double-blind maintenance, and 1-week tapering off. Overall average daily dosage of pregabalin was 385.7 mg/day.

The primary efficacy measure was mean pain score using an 11-point numeric rating scale completed daily by patients; weekly man pain score was a supplemental analysis.

Results

• At the end of the study, patients receiving pregabalin and placebo both showed substantial reductions in mean pain scores from baseline (-2.88 or -42% vs -2.72 or -40%, respectively; P = 0.3941).

• At weeks 1 and 2, patients taking pregabalin had significantly greater improvements in mean pain score relative to placebo:

• Week 1: -1.14 vs -0.69; P = 0.0131;
• Week 2: -1.92 vs 1.43; P = 0.0393.

• At subsequent time points, differences between groups were not statistically significant.

• In an analysis of PGIC scores, more patients taking pregabalin said their condition had improved, and fewer said it had worsened (P = 0.0077):

• 82.8% taking pregabalin and 66.7% taking placebo rated themselves in one of the 3 "improved" categories.

• 13.3% and 25.4%, respectively, experienced "no change."

• 3.9% and 7.9%, respectively, rated themselves in a "worsened" category by the end of the study.

• The most common adverse events (AEs) in the pregabalin arm were somnolence (23.2% pregabalin vs 8.6% placebo) and dizziness (19.2% vs 10.6%, respectively).

• No other AEs were reported by more than 10% of patients taking pregabalin.

• Seven patients (4.6%) in the pregabalin group and 2 patients (1.3%) in the placebo group discontinued because of treatment-related AEs.

Based on these findings, the study authors concluded, "Pregabalin and placebo were associated with substantial improvements in pain and PGIC, with no significant difference in endpoint mean pain score. Adverse events were consistent with the tolerability profile of pregabalin in other neuropathic pain clinical trials."

Mount Sinai Medical Center, New York, NY; Pfizer Global Pharmaceuticals, New York, NY.

8/15/08

Reference

DM Simpson, TK Murphy, E Durso-De Cruz, and others. A randomized, double-blind, placebo-controlled, multicenter trial of pregabalin vs placebo in the treatment of neuropathic pain associated with HIV neuropathy. XVII International AIDS Conference (AIDS 2008). August 3-8, 2008. Mexico City. Abstract THAB0301.