Authors :
Andras Fogarasi, Epilepsy Center, Bethesda Children’s Hospital; Leock Y Ngo - Eisai Inc., Woodcliff Lake, New Jersey, USA; Anna Patten - Eisai Ltd., Hatfield, Hertfordshire, UK; Manoj Malhotra - Eisai Inc., Woodcliff Lake, New Jersey, USA;
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. Study 311 (NCT02849626) was a multicenter, open-label study of adjunctive perampanel oral suspension in pediatric patients (aged 4 to < 12 years) with POS (with or without secondarily generalized seizures [SGS]) or PGTCS. Here, we report efficacy and safety data from patients who converted to perampanel monotherapy during Study 311 (Core and Extension A Phases).
Method:
The Core Study comprised 4-week Pretreatment, 23-week Treatment (11-week Titration; 12-week Maintenance), and 4-week Follow-up Periods (for those not entering Extension A). Extension A comprised 29-week Maintenance and 4-week Follow-up Periods. For this case series of patients who converted to perampanel monotherapy, baseline demographic information was recorded and efficacy assessments included median percent change in seizure frequency per 28 days from baseline and seizure-freedom rates. Safety assessments included reporting treatment-emergent adverse events (TEAEs).
Results:
Overall, 180 patients (POS, n=149 [of which 54 had SGS]; PGTCS, n=31) were enrolled and treated in the Core Study. Of these, 136 patients (POS, n=116; SGS, n=43; PGTCS, n=20) entered Extension A. In total, 4 patients converted to perampanel monotherapy during the study; see Table 1 for an overview of these 4 patients. The median total perampanel treatment duration in these 4 patients was 363 days (range, 337 to 367 days), with patients receiving perampanel adjunctive therapy for a median duration of 203.5 days (range, 186 to 244 days) before converting to perampanel monotherapy (median duration, 152 days; range, 118 to 171 days). The perampanel dose received by these 4 patients at the end of the Core Study (perampanel adjunctive treatment) and at the end of Extension A (perampanel monotherapy) was: Patient 1: 6 and 4 mg/day, respectively; Patient 2: 8 mg/day for both; Patient 3: 14 mg/day for both; Patient 4: 6 and 4 mg/day, respectively. At Weeks 40–52, median percent change in seizure frequency per 28 days from baseline was 100.0% for Patients 1–3 and 75.0% for Patient 4. Only Patient 2 was seizure free at Weeks 40–52. Across both the adjunctive and monotherapy periods, a total of 29 TEAEs were reported in these 4 patients. Twenty-three TEAEs occurred prior to perampanel monotherapy conversion, and 7 occurred during monotherapy treatment.
Conclusion:
In this case series analysis, conversion to perampanel monotherapy provided efficacy and was generally well tolerated in pediatric patients with POS or PGTCS. Further investigation is warranted due to the small sample size.
Funding:
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Funding:
: Eisai Inc.
FIGURES
Figure 1