VANCOUVER, BC—Individual neurocognitive treatment-emergent adverse events (TEAEs) like amnesia, slowed thinking, and speech disorder appear to be relatively rare among patients administered USL255 (Qudexy XR [topiramate] extended-release capsules) for refractory partial-onset seizures (POS), according to findings from a Phase 3 clinical trial and open-label extension study, presented at the 68th AAN Annual Meeting.
“Long-term treatment with up to 400mg/day USL255 was generally well tolerated, with a low incidence (<8%) of individual TEAEs over 55 weeks of treatment,” wrote lead study author Ilan Blatt, MD, of the Chaim Sheba Medical Center in Tel Hashomer, Israel, and coauthors reported in a poster presentation. Of individual neurocognitive TEAEs, “only aphasia occurred in more than 3% of patients during either study.” (Aphasia occurred in 5.2% of patients.) Individual neurocognitive TEAEs leading to discontinuation occurred in less than 1% of patients, they noted.
“These data suggest that once-daily USL255 Qudexy XR extended-release capsules may be a beneficial treatment option for the long-term management of epilepsy,” they concluded.
Previously-reported results from two Phase 3 studies, PREVAIL (NCT01142193) and PREVAIL open-label extension (PREVAIL OLE; NCT01191086) had indicated that USL255 was “well tolerated and efficacious as adjunctive treatment in patients with refractory POS,” Dr. Blatt and colleagues noted.
But because topiramate might be associated with long-term neurocognitive side effects, the researchers analyzed neurocognitive TEAE data from the 2 trials. TEAE frequency, treatment relatedness, and maximum severity were analyzed for a total of 150 patients (71% of originally enrolled participants) who completed both the PREVAIL trial and the PREVAIL OLE study. Two patients each discontinued participation following the emergence of the following TEAEsL aphasia, asthenia, convulsion, and diarrhea.
In PREVAIL, adults with POS had been randomly assigned to receive either placebo or USL255, “titrated over 3 weeks (50mg/week), and maintained at 200mg/day for 8 weeks,” the authors reported. “During an initial 3-week blinded-conversion phase in the OLE, patients randomized to placebo or USL255 in PREVAIL were titrated to 200mg/day USL255 (PBO-USL) or maintained treatment (USL-USL), respectively. OLE continued with a 52-week open-label treatment phase, ≤400mg/day.” TEAEs were evaluated for the first 11 weeks of USL255 treatment and for the duration of the OLE, the authors reported.
During the first 11 weeks of PREVAIL and the OLE, when patients were newly exposed to USL255, overall neurocognitive TEAE incidence was 8.1% among patients who were initially administered USL255 and remained in that category, and 9.9% among patients who were converted from placebo to USL255 during the OLE. “In the entire 55-week OLE, 12.9% of the total study population experienced neurocognitive TEAEs,” they wrote.
The number of patients who experienced at least one neurocognitive TEAE was 6% for patients receiving USL255 throughout both studies, and totaled 18.9% among patients transitioned from placebo to USL255, they reported.
Upsher-Smith Laboratories, Inc. funded the study.