A once-daily controlled-release (CR) formulation of pregabalin (Lyrica, Pfizer) met its main goal in a phase 3 study of patients with fibromyalgia, according to top-line results released by the company this week.
Patients in the study taking once-daily pregabalin CR had a statistically significant positive effect compared with placebo in the primary endpoint of time to loss of therapeutic response, the company said.
However, top-line results from a phase 3 trial of pregabalin CR as adjunctive treatment of partial-onset seizures in adults with epilepsy did not meet its main goal of significantly reducing seizure frequency, the company said.
A phase 3 study testing pregabalin CR in postherpetic neuralgia is ongoing.
"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, said in a statement.
"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," he added.
Promise in Fibromyalgia Study
The fibromyalgia study included 441 patients with fibromyalgia from 49 sites in the United States, Canada, India, and Taiwan.
During a single-blind phase, the optimal dose of pregabalin CR (between 300 and 495 mg once daily) was determined. Of the 441 patients, 122 (28%) completed the single-blind phase, had at least a 50% reduction in pain compared with baseline and entered the double-blind phase, where they continued pregabalin CR or matching placebo.
The primary endpoint was defined as the time to loss of therapeutic pain response (LTR; < 30% pain response relative to the single-blind baseline mean pain or withdrawal due to lack of efficacy or adverse events). It occurred in fewer patients in the pregabalin CR group (34 of 63 [54.0%]) than the placebo group (41 of 58 [70.7%]).
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 = .021).
Pregabalin CR was well tolerated and the safety profile was consistent with the known profile for pregabalin (immediate release) in patients with fibromyalgia, the company said. Adverse events reported in 5% or more of patients included dizziness, somnolence, peripheral edema, insomnia, headache, fatigue, nausea, weight increase, blurred vision, dry mouth, and disturbance in attention.
Disappointment in Seizure Study
Top-line results from the double-blind, placebo-controlled, phase 3 study of pregabalin CR in epilepsy in adults with partial-onset seizures did not meet its primary endpoint comparing the change in seizure frequency to placebo.
The trial tested 165-mg and 330-mg doses once daily. Both doses were well tolerated, the company said. However, there was a nonsignificant reduction in seizure frequency between pregabalin and placebo for the pregabalin CR 330 mg group (P = .0907), the company said.
Responder rates, defined as the percentage of patients with a 50% or greater reduction in seizure frequency from baseline, were 45.9%, 37.8%, and 35.8% for the CR 330 mg, CR 165 mg, and placebo groups, respectively, "and highlight the high placebo response observed in this study," the company said.
Pregabalin is currently approved for various indications in 120 countries and regions globally. In the United States, it is currently approved for 5 indications, 4 of which are in the therapeutic area of pain.
These indications include neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, neuropathic pain associated with spinal cord injury, fibromyalgia, and partial-onset seizures in adults with epilepsy who take 1 or more drugs for seizures.
