PURPOSE: To determine the time at which pregabalin demonstrates seizure-suppressing activity when given as adjunctive treatment to patients with refractory partial seizures. METHODS: Data from four similar 12-week, randomized, double-blind, placebo-controlled, parallel-group trials in patients with refractory partial seizures were pooled to provide an adequate sample to compare the proportion of patients free of seizures on each study day between pregabalin (combined 150-600 mg/day groups) and placebo (combined groups). A generalized estimating equation (GEE) statistical model was used to perform pairwise comparisons on each study day. In several pregabalin dosage groups the dosage was escalated during days 1-7, whereas in others pregabalin was initiated at a fixed dosage without escalation. RESULTS: The proportion of patients free of seizures on any treatment day was greater in the combined pregabalin groups compared with baseline. Differences were not observed between the placebo group and baseline. A significantly greater proportion of patients were free of seizures in the combined pregabalin 150-600 mg/day and the pregabalin 600 mg/day fixed-dosage groups compared with the placebo groups from treatment day 2 onward (p < 0.05). From day 8 (coinciding with completion of the 1-week dosage-escalation period in two studies) onward, the proportion of patients free of seizures per day in the pregabalin groups remained relatively constant. DISCUSSION: This exploratory analysis of a refractory population using a rigorous endpoint demonstrates that pregabalin rapidly reduced the frequency of partial seizures. At the dosing schemes most commonly used in placebo-controlled trials, significant seizure-suppressing activity was observed after only 2 days of treatment.
RCT Entities:
PURPOSE: To determine the time at which pregabalin demonstrates seizure-suppressing activity when given as adjunctive treatment to patients with refractory partial seizures. METHODS: Data from four similar 12-week, randomized, double-blind, placebo-controlled, parallel-group trials in patients with refractory partial seizures were pooled to provide an adequate sample to compare the proportion of patients free of seizures on each study day between pregabalin (combined 150-600 mg/day groups) and placebo (combined groups). A generalized estimating equation (GEE) statistical model was used to perform pairwise comparisons on each study day. In several pregabalin dosage groups the dosage was escalated during days 1-7, whereas in others pregabalin was initiated at a fixed dosage without escalation. RESULTS: The proportion of patients free of seizures on any treatment day was greater in the combined pregabalin groups compared with baseline. Differences were not observed between the placebo group and baseline. A significantly greater proportion of patients were free of seizures in the combined pregabalin 150-600 mg/day and the pregabalin 600 mg/day fixed-dosage groups compared with the placebo groups from treatment day 2 onward (p < 0.05). From day 8 (coinciding with completion of the 1-week dosage-escalation period in two studies) onward, the proportion of patients free of seizures per day in the pregabalin groups remained relatively constant. DISCUSSION: This exploratory analysis of a refractory population using a rigorous endpoint demonstrates that pregabalin rapidly reduced the frequency of partial seizures. At the dosing schemes most commonly used in placebo-controlled trials, significant seizure-suppressing activity was observed after only 2 days of treatment.
Authors: Andrea O Rossetti; Sandrine Jeckelmann; Jan Novy; Patrick Roth; Michael Weller; Roger Stupp Journal: Neuro Oncol Date: 2013-12-04 Impact factor: 12.300