Once-Daily Lyrica (Pregabalin) Fails to Meet Treatment Goal in Phase III Trial
Reduction in seizure frequency was non-significant versus placebo (Nov. 16)
A controlled-release (CR) formulation of Lyrica (pregabalin, Pfizer) did not meet its primary endpoint of the change in seizure frequency compared with placebo in a phase III, double-blind trial that evaluated pregabalin CR 165 mg and 330 mg in adult epileptic patients with partial-onset seizures.
Epilepsy is a chronic disorder in which seizures occur intermittently. Partial-onset seizures (simple, complex, and secondarily generalized tonic-clonic) are the most common. In the U.S., the immediate-release formulation of Lyrica (pregabalin) capsules CV has been used as adjunctive therapy for partial-onset seizures since the drug’s approval in June 2005.
The objective of the new double-blind, randomized, parallel group, multicenter study was to assess the efficacy and safety of pregabalin CR as adjunctive treatment of partial-onset seizures in adult patients with epilepsy.
The study consisted of four phases: 1) an 8-week baseline phase, during which the baseline seizure rate was recorded; 2) a 2-week double-blind dose-escalation phase; 3) a 12-week double-blind maintenance phase, during which the dosage of study medication was fixed; and 4) a 1-week taper phase at the conclusion of the study. The treatment groups included pregabalin CR 165 mg/day, pregabalin CR 330 mg/day, and placebo. The pregabalin CR dose levels provided exposures similar to those of 150-mg and 300-mg daily doses of currently available Lyrica (pregabalin) immediate-release formulations.
The study’s primary endpoint was the 28-day seizure rate for all partial-onset seizures collected during the double-blind treatment phase, compared with the 8-week baseline (screening) seizure period.
The analysis of the primary endpoint showed a non-significant result between pregabalin and placebo for the pregabalin CR 330-mg group (P = 0.0907). Responder rates — defined as the percentage of patients with ≥ 50% reduction in seizure frequency from baseline — were 46%, 38%, and 36% for the CR 330 mg, CR 165 mg, and placebo groups, respectively.
Both the 165-mg and 330-mg doses of pregabalin CR were well tolerated. The most common adverse events were dizziness, increased weight, and somnolence.
Source: Pfizer; November 16, 2012.