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

Abstract

In this double-blind, two-period, crossover trial with randomized treatment assignment, progabide (+/- 30 mg/kg/day) and placebo were compared as add-on to standard therapy in 20 "therapy-resistant" epileptic patients (11 males, nine females; age range, 7-47 years). The duration of each treatment period was 6 weeks. Crossover was performed gradually over 3-4 days. Twenty-four patients entered the study: three dropped out for reasons unrelated to progabide effects; one dropped out during the placebo period because of increased seizure frequency. Of the 20 patients who completed the study, 14 had partial, two partial plus secondary generalized, and four generalized seizures. Preexisting antiepileptic treatment consisted of one antiepileptic drug (AED) in three, two AEDs in eight, three AEDs in five, and four AEDs in four patients (mean, 2.5 AEDs/patient). The following parameters were recorded at biweekly intervals: (a) efficacy parameters--total seizure count, counts of each seizure type, and global clinical judgment; (b) safety parameters--adverse drug effects, brief clinical and neurological examinations, and laboratory tests; and (c) plasma concentrations of progabide and of the associated AEDs. Twelve patients were considered to be improved (p less than 0.01) with progabide by global clinical judgment compared with two patients improved with placebo. Nine patients of 20 had a 48-100% reduction of total seizure count in the verum 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 less than 0.05). Adverse effects were reported or observed in 10 patients during the progabide period and in five patients in the placebo period. The side effects were generally mild and consisted of somnolence in four 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 two cases only. No treatment-related alterations in results of laboratory tests were observed.

Reappraisal of Polytherapy in Epilepsy: A Critical Review of Drug Load and Adverse Effects

“…Combined data from the studies cited (22)(23)(24)(25)(26). From the published data, one measurement per patient was taken at random.…”

“…In five articles, the number and dose of all AEDs (but not serum levels) and AE were reported per patient (22)(23)(24)(25)(26). The total AED load in relation to the number of AE in individual patients is shown in Fig.…”

Double‐Blind Withdrawal of Phenytoin and Carbamazepine in Patients Treated with Progabide for Partial Seizures

“…Some of the European clinical trials have shown it to be effective (Van der Linden et al, 1981;Loiseau et al, 1983;Weber et a]., 1983;Martinez-Lage et al, 1984), while results of other studies have been less favorable (Dam et al, 1983;Schmidt, 1984). PGB was the first drug to be tested by the Epilepsy Branch of the National Institutes of Health (NIH) under the Antiepileptic Drug Development Program (Leppik et al, 1985).…”

Progabide: A Controlled Trial in Partial Epilepsy

“…The drug was evaluated in two controlled studies of patients with severe epilepsy, both suggesting a positive effect (Loiseau et al, 1981;van der Linden et a]., 1981).…”