Rationale:
In the US and Japan, perampanel is approved for partial-onset seizures (POS; adjunctive and monotherapy) in patients aged ≥ 4 years, and adjunctive treatment of primary generalized tonic-clonic seizures in patients aged ≥ 12 years. To assess the long-term efficacy and safety of perampanel, patients with POS (with or without secondarily generalized seizures [SGS]) who completed placebo-controlled Phase III studies of adjunctive perampanel could enter OLEx Studies 307 (NCT00735397) and 335 OLEx (NCT01618695). Here, we report the long-term (up to 4 years) efficacy and safety of perampanel in a post hoc analysis of elderly patients (aged ≥ 60 years) with POS, with or without SGS, from these OLEx studies.
Method:
Study 307 comprised a 16-week blinded Conversion Period and a 256-week Maintenance Period. Study 335 OLEx comprised 4-week Pre-conversion, 6-week Conversion, and at least 46-week Maintenance Periods. During the OLEx studies, patients received perampanel 2–12 mg/day. Efficacy assessments included median percent reduction in seizure frequency per 28 days vs pre-perampanel baseline, and 50% responder and seizure-freedom rates, at Years 1, 2, 3, and 4. Safety assessments included monitoring of treatment-emergent adverse events (TEAEs).
Results:
The Safety Analysis Set included 71 elderly patients aged ≥ 60 years with POS (mean [standard deviation] age, 64.0 [3.8] years; female, 60.6%); of these, 19 patients had POS with SGS. At baseline, 11.3% (n=8), 46.5% (n=33), and 42.3% (n=30) of patients received 1, 2, or 3 anti-seizure medications, respectively. For total POS and POS with SGS, reductions in seizure frequency were observed over 4 years, with more than one-third of patients achieving a ≥ 50% reduction in seizure frequency (Figures 1A–B); during Years 1 and 2, median percent reductions in seizure frequency for POS with SGS were > 95% (Figure 1A). Seizure-freedom rates for total POS during Years 1, 2, 3, and 4 were 0.0% (n=0/71), 2.6% (n=1/38), 5.3% (n=1/19), and 0.0% (n=0/14), and for SGS were 26.3% (n=5/19), 22.2% (n=2/9), 40.0% (n=2/5), and 0.0% (n=0/4), respectively; however, the small patient numbers at later time points should be taken into consideration when interpreting these data. During Years 1, 2, 3, and 4, respectively, 87.3% (n=62/71), 60.4% (n=29/48), 47.4% (n=9/19), and 57.1% (n=8/14) of patients experienced TEAEs. The most common TEAE during Years 1 and 2 was dizziness (n=34 [47.9%] and n=6 [12.5%], respectively), and during Years 3 and 4 was fall (n=3 [15.8%] and n=2 [14.3%], respectively).
Conclusion:
In this post hoc analysis of adjunctive perampanel in elderly patients aged ≥ 60 years from Studies 307 and 335 OLEx, reductions in seizure frequency were observed over 4 years for both POS and SGS; the safety profile was consistent with the overall populations, and no new safety signals emerged during long-term treatment.
Funding:
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Funding:
: Eisai Inc.
FIGURES
Figure 1