Pfizer announced top-line results from a double-blind Phase III study evaluating pregabalin controlled-release (CR) formulation in adult patients with postherpetic neuralgia (pain after shingles or PHN).
The results show that pregabalin CR resulted in a statistically significant positive effect compared to placebo in the primary endpoint, time to loss of therapeutic response (LTR) in pain reduction.
PHN is a type of peripheral neuropathic pain caused by nerve damage. Symptoms include continued burning or electric shock-like pain.
This study is the final of three Phase 3 studies of the pregabalin CR formulation conducted to ascertain the potential use of pregabalin as a once-a-day therapy.
The first study in adults with partial onset seizures with epilepsy did not meet its primary endpoint. In the second study in patients with fibromyalgia, pregabalin CR had a statistically significant positive effect compared to placebo in the primary endpoint, time to LTR in pain reduction.
The objective of the Phase 3 double-blind, randomized, placebo-controlled study was to evaluate the safety and efficacy of pregabalin CR compared with placebo in the durability of effect for the treatment of pain associated with PHN among patients who initially respond to single-blind pregabalin.
The study was composed of 4 phases: baseline (1 week), single-blind treatment (6 weeks), double-blind treatment (13 weeks), and a 1-week double-blind taper.
During the single-blind phase, there were two stratification groups receiving different doses of pregabalin. Patients with normal renal function received a dose between 165 mg/day to 660 mg/day while patients with low renal function received between 82.5 mg/day and 330 mg/day of pregabalin.
In the double-blind phase, patients were randomized to continued pregabalin CR treatment at the optimized dose or to matching placebo.
A total of 796 subjects were enrolled into the single-blind phase from 116 sites in 17 countries. Of the 796 subjects, 418 (51.8%) completed the single-blind phase, had =50% pain response (i.e., =50% reduction in pain compared to baseline) and were randomized into double-blind phase.
The primary endpoint, defined as the time to LTR during the double-blind phase (LTR; <30% pain response relative to the baseline mean pain or withdrawal due to lack of efficacy or adverse events), occurred in 29 of 208 (13.9%) patients in the pregabalin group as compared with 63 of 205 (30.7%) subjects in the placebo group. The difference between the treatments was statistically significant.
Pregabalin CR was well tolerated and the safety profile was consistent with the known profile for pregabalin (immediate release) in PHN patients. The most common adverse events with pregabalin CR were dizziness, somnolence, peripheral edema and weight increase.
Full results from the study will be submitted for publication when analyses are complete.