[P3.263] Efficacy of USL255 Across Partial-Onset Seizure Types and Refractory Patient Status: Subgroup Analyses From the PREVAIL Study
Ilan Blatt,1Venkatesh Nagaraddi,2Robert Hogan,3Stephan Arnold,4Balduin Lawson,5Bob Anders,6Annie M. Clark,6Mark Halvorsen,6Steve Chung7
1Tel Hashomer, Israel, 2Dallas, TX, USA, 3Saint Louis, MO, USA, 4Münich, Germany, 5Santiago, Chile, 6Maple Grove, MN, USA, 7Phoenix, AZ, USA
OBJECTIVE: Assess the efficacy of USL255, once-daily extended-release topiramate, in patients subdivided by baseline seizure type and antiepileptic drug (AED) use.
BACKGROUND: Seizure type, concomitant AED use, and the number of previous AEDs may influence responsiveness of a patient to AED treatment. These analyses attempt to identify effectiveness of USL255 in treatment-resistant patient subgroups.
DESIGN/METHODS: In this double-blind, phase 3 study (PREVAIL; NCT01142193), patients with partial-onset seizures (POS) on 1-3 concomitant AEDs were randomized to placebo (n=125) or USL255 (n=124), titrated over 3 weeks (50 mg/week), and maintained at 200 mg/day for 8 weeks. Efficacy assessments included median percent reduction from baseline in weekly POS frequency and 50% responder rate. Subgroup analyses included efficacy by 1) POS seizure type, 2) concomitant AED use, 3) lifetime AED use, and 4) refractory status ('highly refractory', ≥2concomitant AEDs and ≥4 lifetime AEDs; 'less refractory', 1 concomitant AED or <4 lifetime AEDs), although PREVAIL was not powered for statistical analyses in these subgroups.
RESULTS: In subjects experiencing disabling seizures (complex partial with/without secondary generalization), USL255 significantly reduced weekly seizure frequency (40.6% vs 17.7%; P<.001) and increased responder rate (42.0% vs 20.9%; P=.001) vs placebo. Both seizure reduction and responder rate were significantly improved in patients concurrently taking ≥3 AEDs (P<.001 for both) and those who had tried ≥4 AEDs over their lifetime (P=.001 and .007, respectively). In patients deemed 'highly refractory', reduction in seizure frequency was 2-fold higher with USL255 vs placebo (40.4% vs 18.1%; P=.004) and responder rate was significantly improved (38.5% vs 19.0%; P=.023).
CONCLUSIONS: USL255 was efficacious as an adjunctive treatment for POS, with a variety of concomitant AEDs, and in highly refractory patients. Results from the PREVAIL study demonstrate broad and consistent efficacy of USL255, which may provide a significant benefit to patients with epilepsy.
Study Supported by: Upsher-Smith Laboratories, Inc.
Category - Epilepsy and Clinical Neurophysiology (EEG): Therapeutics: Medical
Tuesday, April 29, 2014 3:00 PM
P3: Poster Session III: Epilepsy and Clinical Neurophysiology: AED (3:00 PM-6:30 PM)