Pfizer announced top-line results from a double-blind phase 3 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, randomised, 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 randomised to continued pregabalin CR treatment at the optimised 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 per cent ) completed the single-blind phase, had =50 per cent pain response (i.e., =50 per cent reduction in pain compared to baseline) and were randomised into double-blind phase.
The primary endpoint, defined as the time to LTR during the double-blind phase (LTR; <30 per cent 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 per cent ) patients in the pregabalin group as compared with 63 of 205 (30.7 per cent ) 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.
Lyrica is currently approved for various indications in 120 countries and regions globally.Lyrica is approved for five indications in the US, of which four are in the therapeutic area of pain. These indications include neuropathic pain associated with diabetic peripheral neuropathy, post-herpetic neuralgia (pain after shingles), neuropathic pain associated with spinal cord injury, fibromyalgia and partial onset seizures in adults with epilepsy who take one or more drugs for seizures.
Lyrica’s ongoing clinical development program is focused on the significant unmet needs of patients with certain chronic pain conditions.
Antiepileptic drugs (AEDs), including Lyrica, increase the risk of suicidal thoughts or behavior in patients taking AEDs for any indication. There have been post-marketing reports of angioedema and hypersensitivity with Lyrica. Treatment with Lyrica may cause dizziness, somnolence, dry mouth, edema and blurred vision. Other most common adverse reactions include weight gain, constipation, euphoric mood, balance disorder, increased appetite and thinking abnormal (primarily difficulty with concentration/attention).