Double-Blind Crossover Trial of Progabide Versus Placebo in Severe Epilepsies

Abstract

In this double-blind, 2-period, crossover trial with randomized treatment assignment, progabide (.+-. 30 mg/kg per day) and placebo were compared as add-on to standard therapy in 20 therapy-resistant epileptic patients (11 males, 9 females; age range, 7-47 yr). The duration of each treatment period was 6 wk. Crossover was performed gradually over 3-4 days. Twenty-four patients entered the study: 3 dropped out for reasons unrelated to progabide effects; 1 dropped out during the placebo period because of increased seizure frequency. Of the 20 patients who completed the study, 14 had partial, 2 partial plus secondary generalized and 4 generalized seizures. Preexistent antiepileptic treatment consisted of 1 antiepileptic drug (AED) in 3, 2 AED in 8, 3 AED in 5, and 4 AED in 4 patients (mean, 2.5 AED/patient). The following parameters were recorded at biweekly intervals: efficacy parameters, total seizure count, counts of each seizure type, and global clinical judgment; safety parameters, adverse drug effects, brief clinical and neurological examinations, and laboratory tests; and plasma concentrations of progabide and of the associated AED. Twelve patients were considered to be improved (P < 0.01) with progabide by global clinical judgment compared with 2 patients improved with placebo. Of 20, 9 patients had a 48-100% reduction of total seizure count in the verum [experimental] period, leading to a significant reduction of total seizure number and of complex partial seizures in the verum period as compared with the placebo period (P < 0.05). Adverse effects were reported or observed in 10 patients during the progabide period, and in 5 patients in the placebo period. The side effects were generally mild and consisted of somnolence in 4 cases and of tremors, dry mouth, troubles of equilibrium, anorexia, euphoria, depression and anxiety in individual patients: a 15-20% reduction of the progabide dose was required in 2 cases only. No treatment-related alterations in results of laboratory tests were observed.