Abstracts

Rationale:
In the US, perampanel is approved for the treatment of partial-onset seizures ([POS], adjunctive and monotherapy) in patients aged ≥ 4 years, and as adjunctive treatment of primary generalized tonic-clonic seizures (PGTCS) in patients aged ≥ 12 years. Data from prospective clinical studies on perampanel as monotherapy or early adjunctive therapy are limited as Phase III registration studies evaluated perampanel as adjunctive therapy in patients who were treatment-resistant. ELEVATE (Study 410; NCT03288129) is an ongoing 12-month, multicenter, open-label, Phase IV study (Figure 1) that is the first prospective study of perampanel administered as monotherapy or first adjunctive therapy in patients aged ≥ 4 years with POS, with or without secondarily generalized seizures (SGS), or PGTCS. Here, we provide an update on the demographics and initial results from patients enrolled in ELEVATE.
Method:
During Titration, perampanel 2 mg/day will be taken and uptitrated to 4 mg/day based on clinical response and tolerability; patients could receive ≤ 12 mg/day depending on their need for additional efficacy (titration: 2-mg/day increments at a minimum of 2-week intervals). Patients receiving enzyme-inducing ASMs could be uptitrated in 2-mg/day increments at 1-week intervals. Primary endpoint is retention rate at 3, 6, 9, and 12 months. Secondary endpoints include safety and seizure-freedom. Baseline seizure counts will be collected retrospectively and prospectively for the 12-week period prior to first dose, and seizure diaries will be used to collect seizure counts during the study.
Results:
As of May 15, 2020, data are available for 13 patients from 24 sites across the US; POS, n=10; SGS; n=1; PGTCS, n=3. No patients discontinued the study. The mean age (SD) of the patients was 45.2 (14.2) years; additional baseline characteristics are shown in Table 1. Compliance rates > 90%, 80% to < 90% and 70% to < 80% were observed in 69.2% (n=9/13),  7.7% (n=1/13) and 23.1% (n =3/13) of patients, respectively. Mean (SD) compliance rates were 93.2 (12.5) in the total patient population. Four patients received perampanel as monotherapy and 9 patients as first adjunctive therapy; no patients converted to monotherapy. The last dose of perampanel received was 4 mg (n=3), 6 mg (n=2), 8 mg (n=6), 10 mg (n=1) and 12 mg (n=1). TEAEs occurred in 11/13 (84.6%) of patients enrolled in the Study; no adverse events led to study withdrawal.
Conclusion:
The initial results of ELEVATE show that patients were compliant with perampanel treatment and perampanel was well tolerated. Additional analyses, including efficacy analyses are being conducted and will be presented at a later date.
Funding:
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Funding:
: Eisai Inc.