Pfizer Inc. has reported top-line results of a double-blind, phase III study evaluating pregabalin controlled-release (CR) formulation in patients with fibromyalgia indicate that pregabalin CR had a statistically significant positive effect compared to placebo in the primary endpoint, time to loss of therapeutic response (LTR). Fibromyalgia is a common pain condition in the United States, and is characterized by chronic widespread pain and tenderness lasting for three or more months.
This study is the second of three phase III studies of the pregabalin CR formulation to report top-line findings, which will ascertain the potential use of pregabalin as a once-a-day therapy. The top-line results of the first study in adults with partial onset seizures with epilepsy did not meet its primary endpoint. The final study in post-herpetic neuralgia is ongoing. Pfizer will analyse further results of all three studies once data are available.
“Collectively, the results of these controlled release studies will allow us to better understand the potential of a once-a-day pregabalin treatment regimen,” said Steven J Romano, MD, senior vice president, head, Medicines Development Group, Global Primary Care Business Unit, Pfizer Inc. “Reducing the number of times patients need to take their medicine per day while maintaining the same efficacy and safety profile could potentially provide a greater convenience and the potential to enhance treatment adherence and outcomes.”
The objective of the double-blind, placebo-controlled, multi-centre, randomized withdrawal study was to assess the efficacy and safety of pregabalin CR as treatment for patients with fibromyalgia.
The study was composed of four phases: baseline (one week), single-blind (SB) treatment (six weeks), double-blind (DB) treatment (13 weeks), and a one-week double-blind taper. Study medication was administered once daily (QD) immediately following the evening meal. During the SB phase, an optimal dose of pregabalin CR (between 300 mg/day to 495 mg/day) was determined. In the DB phase, patients were randomized to continued pregabalin CR treatment at the optimized dose or to matching placebo.
A total of 441 subjects were enrolled into the SB phase from 49 sites in four countries (US, Canada, India, and Taiwan). Of the 441 subjects, 122 (28 per cent) completed SB, had =50 per cent pain response (i.e., =50 per cent reduction in pain compared to baseline) and were randomized into DB. 122 subjects completed the single-blind phase and were randomized to the double-blind phase. One subject discontinued following randomization without receiving double-blind study medication, so 121 subjects received double-blind study medication and are included in the full analysis set.
The primary endpoint, defined as the time to loss of therapeutic pain response during DB (LTR; <30 per cent pain response relative to the SB baseline mean pain or withdrawal due to lack of efficacy or adverse events), occurred in 34 of 63 (54.0 per cent) patients in the pregabalin group as compared with 41 of 58 (70.7 per cent) subjects in the placebo group. The median time from randomization to LTR was 58 days in the pregabalin group and 22 days in the placebo group. The difference between the treatments was statistically significant (log-rank p-value=0.021).
Pregabalin CR was well tolerated and the safety profile was consistent with the known profile for pregabalin (immediate release) in fibromyalgia patients. Adverse events reported in five per cent or more of subjects included dizziness, somnolence, peripheral oedema, insomnia, headache, fatigue, nausea, weight increased, vision blurred, dry mouth, and disturbance in attention.
Lyrica is currently approved for various indications in 120 countries and regions globally. Since its first approval from the FDA in 2004, Lyrica has been 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. Anti-epileptic drugs (AEDs) including Lyrica increase the risk of suicidal thoughts or behaviour 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, oedema 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).
Pfizer strives to set the standard for quality, safety and value in the discovery, development and manufacturing of medicines for people and animals. Its diversified global health care portfolio includes human and animal biologic and small molecule medicines and vaccines, as well as nutritional products and many of the world’s best-known consumer products.