Abstracts

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 (PGTCS) in patients aged ≥ 12 years. Here, we present a post hoc analysis of the efficacy and safety of adjunctive perampanel in Japanese patients with POS, with/without secondarily generalized seizures (SGS), or PGTCS from double-blind studies (Phase II: 235; Phase III: 304, 305, 306, 335, 332) and their open-label extension (OLEx) phases (235 OLEx, 307, 335 OLEx, 332 OLEx).
Method:
For this post hoc analysis, efficacy assessments were based on the Full Analysis Set and included median percent reductions in seizure frequency per 28 days from baseline, and 50% responder and seizure-freedom rates. Treatment-emergent adverse events (TEAEs) were assessed in the Safety Analysis Set using pooled data for all seizure types.
Results:
The Full and Safety Analysis Sets included 256 Japanese patients (placebo, n=66; perampanel, n=190). Across double-blind studies, median percent reductions in seizure frequency per 28 days (placebo vs perampanel) were 10.5% (n=60) vs 18.8% (n=185) for POS and 1.6% (n=18) vs 23.9% (n=51) for SGS at 4–12 mg/day, and 56.5% (n=6) vs 67.9% (n=5) for PGTCS at 8 mg/day. Corresponding 50% responder rates were 10.0% (n=6/60) vs 29.2% (n=54/185), 22.2% (n=4/18) vs 39.2% (n=20/51), and 50.0% (n=3/6) vs 60.0% (n=3/5) for POS, SGS, and PGTCS, respectively. Seizure-freedom rates were 0.0% (n=0/60) vs 1.6% (n=3/185), 0.0% (n=0/18) vs 9.8% (n=5/51), and 33.3% (n=2/6) vs 20.0% (n=1/5), respectively. Across double-blind studies, TEAEs occurred in 47 (71.2%) placebo-treated and 157 (82.6%) perampanel-treated patients; with perampanel, the most common TEAEs were somnolence (n=47 [24.7%]), nasopharyngitis (n=43 [22.6%]), and dizziness (n=40 [21.1%]). Overall, 251 patients entered the OLEx studies (POS, n=241; SGS, n=71; PGTCS, n=10). During Year 1, median percent reductions in seizure frequency per 28 days were: POS, 18.2% (n=241); SGS, 29.4% (n=71); PGTCS, 87.7% (n=10). Fifty-percent responder rates were: POS, 22.0% (n=53/241); SGS, 32.4% (n=23/71); PGTCS, 70.0% (n=7/10). Seizure-freedom rates were: POS, 0.4% (n=1/241); SGS, 9.9% (n=7/71); PGTCS, 30.0% (n=3/10). TEAEs occurred in 74/251 (29.5%) patients during the OLEx studies. Consistent with double-blind studies, the most common TEAEs were nasopharyngitis (n=37 [14.7%]), somnolence (n=32 [12.7%]), and dizziness (n=22 [8.8%]).
Conclusion:
Efficacy and safety outcomes with adjunctive perampanel during double-blind studies in Japanese patients were generally consistent with results from overall Phase II and III patient populations. Seizure control was maintained during long-term (1-year) treatment for POS (with/without SGS) and PGTCS.
Funding:
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Funding:
: Eisai Inc.