Efficacy and Safety of USL255, Qudexy® XR (Topiramate) Extended-Release Capsules, and Second-Generation AEDs (P3.248)

Objective: Compare efficacy and safety of once-daily USL255 (Qudexy ® XR [topiramate] extended-release capsules) and other second-generation antiepileptic drugs (AEDs). Background: USL255 has demonstrated efficacy and safety in phase 3 studies (PREVAIL [NCT01142193]; PREVAIL OLE [NCT01191086]). However, a crowded field of >20 AEDs and increasing placebo rates present challenges comparing study results. Design/Methods: In PREVAIL, patients with partial-onset seizures (POS) taking 1–3 concomitant AEDs were randomized to placebo or USL255 (3-week titration [50 mg/wk] and 8-week maintenance [200 mg/d]). PREVAIL efficacy results were compared with a study of similar design evaluating add-on TPM-IR (Guberman et al, 2002). PREVAIL adverse events (AEs) were compared with those reported in prescribing information for lacosamide (LCM), lamotrigine (LTG), levetiracetam (LEV), oxcarbazepine (OXC) and immediate- release topiramate (TPM-IR); AE risk ratios (RR) were calculated. Results: USL255 resulted in significantly greater median percent reduction from baseline in POS frequency versus placebo (PREVAIL: 39.5% versus 21.7%, P P =.013); TPM-IR versus placebo results were similar (Guberman 2002: 52% versus 20%, P P Conclusions: USL255 demonstrated similar efficacy to a TPM-IR study from 2002, when the number of AEDs were limited and placebo response rates generally lower. USL255 is associated with a relatively low rate of AEs compared to newer AEDs. Despite introduction of multiple AEDs, USL255 may provide benefit for patients with epilepsy with a favorable safety profile. Study Supported by: Upsher-Smith Laboratories, Inc. Disclosure: Dr. Chung has received personal compensation for activities with UCB Pharma, Eisai, Lundbeck, Upsher-Smith, and Sunovion. Dr. Chung has received research support from Lundbeck, UCB Pharma, Upsher-Smith, and SK Life Sciences. Dr. Hogan has received personal compensation for activities with Upsher-Smith Pharmaceuticals. Dr. Hogan has received research support from Eisai Pharmaceuticals, Upsher-Smith Pharmaceuticals, UCB Pharmaceuticals, Neurelis Pharmaceuticals, and Pfizer Pharmaceuticals. Dr. Blatt has received personal compensation for activities with Upsher-Smith Laboratories, Inc. Dr. Lawson has received personal compensation for activities with Upsher-Smith Laboratories Inc. as a consultant. Dr. Halvorsen has received personal compensation for activities with Upsher-Smith Laboratories, Inc. as an employee.