Abstracts

SPM 927 is being developed by Schwarz Biosciences as an oral and intravenous formulation for the treatment of partial seizures and neuropathic pain. An ongoing Phase 2 extension trial (SP615) is being conducted. The aim of the current evaluation is to describe the safety and efficacy profile of SPM 927 following the first four weeks of dosing in the extension trial. The subjects included in the evaluation completed an ongoing, double-blind, dose-ranging trial (SP667) prior to enrolling in the extension trial.
The double-blind trial enrolled subjects who had uncontrolled partial seizures ([ge] 4 seizures per 28 days) and had been taking a stable regimen of up to two antiepileptic drugs (AEDs) with or without additional concurrent vagus nerve stimulation. Subjects were titrated to their randomized dose in the double-blind trial. Subjects who completed a 12-week maintenance period were offered SPM 927 in the extension trial. Those subjects choosing to participate in the extension trial were transitioned to a common dose (200 mg/day) over a 2-week period at the end of the double-blind trial. The transition was performed in a double-blind fashion. Once the subjects were enrolled in the extension trial, the investigators could increase or decrease the dose of SPM 927 (100 to 600 mg/day) and concomitant AEDs at their discretion. At the end of Week 4, efficacy was evaluated by calculating both the percent change in partial seizure frequency (per 28 days) from baseline of the double-blind trial and the 50% responder rate.
A total of 28 subjects (13 females and 15 males) had available efficacy data for the first four weeks of the extension trial. The mean age of the subjects at entry was 40.9 years. The median number of years since being diagnosed with epilepsy was 27.9 years. Of the 28 subjects, 13 subjects exclusively took 200 mg/day SPM 927 throughout the first four weeks of the trial. Doses for the remaining subjects ranged from 100 to 400 mg/day during the four weeks.
None of the 28 subjects discontinued during the first four weeks. In addition, no serious adverse events were reported. Adverse events reported during the trial were most frequently CNS-related and mild or moderate in severity.
The median percent seizure reduction at Week 4 was 43%. For subjects who exclusively took 200 mg/day SPM 927 during the first month, the median percent seizure reduction was 44%. Nine of the 28 subjects (32%) were 50% responders. One of these nine subjects was seizure free throughout the first four weeks of the trial.
SPM 927 has been well tolerated as adjunctive therapy during the first four weeks of an ongoing open-label extension trial among subjects enrolled from an ongoing, double-blind trial, with no subjects discontinuing. Subjects on SPM 927 have shown seizure reductions during this extension trial.
[Supported by: Schwarz Biosciences Inc. VB received a research grant and honorarium for this trial.]