Abstracts

Rationale: USL255, Qudexy™ XR (topiramate) extended-release capsules, was formulated to provide consistent drug release and reduced plasma fluctuations compared with immediate-release topiramate. USL255 was recently approved as a once-daily treatment for epilepsy (monotherapy for partial-onset seizures [POS] or primary generalized tonic-clonic [PGTC] seizures in patients ≥10 yr; adjunctive therapy for POS, PGTC, or seizures associated with Lennox-Gastaut syndrome in patients ≥2 yr). USL255 demonstrated efficacy and favorable tolerability as adjunctive treatment for refractory POS in a randomized, double-blind, placebo-controlled, phase 3 study (PREVAIL; NCT01142193). Long-term safety and tolerability data for USL255 from the 1-year PREVAIL open-label extension (OLE; NCT01191086) study are presented here. Methods: Patients who completed the 11-week double-blind treatment phase of PREVAIL were eligible to enroll in the OLE. Participants underwent a 3-week blinded-conversion phase, during which patients randomized to placebo in PREVAIL were titrated to 200 mg/d USL255 (50 mg/wk), and those randomized to 200 mg/d USL255 in PREVAIL were given matching placebo. The conversion phase was followed by a 52-week open-label treatment phase. After 11 weeks of treatment, changes in USL255 dosage (in 50 mg/wk increments to a maximum of 400 mg/d) and concomitant AEDs were allowed. Incidence and severity of spontaneously-reported treatment-emergent adverse events (TEAEs) were assessed during the OLE and up to 30 days after the last dose of study medication. Neurocognitive and neuropsychiatric TEAEs reported by study participants were also summarized. Results: Of the 217 subjects who completed PREVAIL, 210 (96.8%) enrolled in the OLE. The OLE completion rate was 70% (148 patients), with 9.5% of patients discontinuing due to TEAEs. The overall incidence of participants reporting at least one TEAE was 70%, with the majority reported as mild-to-moderate in severity. The most common TEAEs (≥5% of all patients) were headache (7.6%), weight decrease (7.6%), somnolence (7.1%), dizziness (6.2%), aphasia (5.2%), and fatigue (5.2%). Similar to the rate in the 11-week treatment phase of PREVAIL, the incidence of individual neurocognitive or neuropsychiatric TEAEs newly reported during the year-long OLE was less than 3%, with the exception of aphasia (5.2%) and depression (3.8%). A total of 14 (6.7%) of patients reported 18 serious adverse events. One death occurred (ischemic stroke) and was deemed unrelated to study drug. Conclusions: Treatment with USL255 at dosages up to 400 mg/d during the 1-year PREVAIL OLE was generally well tolerated in patients with refractory POS. The low incidence of individual neurocognitive and neuropsychiatric TEAEs, combined with the overall favorable safety profile, suggest USL255 may provide a safe, once-daily option for the long-term treatment of epilepsy. Supported by Upsher-Smith Laboratories, Inc.