A Phase 4, multicenter, prospective, non-interventional, observational study to investigate the effectiveness and safety/tolerability of perampanel when used as first adjunctive therapy in routine clinical practice in people with epilepsy: Study 512

Abstract

Introduction: Study 512 aimed to assess the efficacy and safety of perampanel (PER) as the first add-on therapy.

Methods: In this 12-month, prospective, observational, multicenter study, people with epilepsy (PWE) aged ≥12 years with focal-onset seizures or generalized tonic-clonic seizures (GTCS) associated with idiopathic generalized epilepsy received PER as the first add-on therapy to antiseizure medication (ASM) monotherapy. The primary efficacy endpoint was the retention rate at 12 months. Other endpoints included change in seizure frequency from baseline; pragmatic seizure freedom rate (proportion of PWE in the full analysis set achieving freedom from all seizures); responder rate (≥50% seizure frequency reduction from baseline), changes from baseline in the 10-item Quality of Life in Epilepsy questionnaire (QOLIE-10) total score, the Epworth Sleepiness Scale (ESS), and the age-corrected EpiTrack and EpiTrack Junior total score; safety/tolerability (treatment-emergent adverse events [TEAEs]); and PER dose.

Results: Of 184 PWE (Safety Set, n = 182; Full Analysis Set, n = 174), 135 (73.4%) completed the 12-month study. The mean PER dose was 4.7 mg/day. Retention rate at 12 months was 74.2% in the overall population, 81.8% in the 12 to <18 years age group, 74.3% in the 18 to <65 years age group, and 66.7% in the ≥65 years age group. Retention rates were similar between PWE with focal-onset seizures (74.5%) and GTCS (75.0%). The median reduction in monthly seizure frequency per 28 days from baseline to 12 months was 78.6% in the overall population, 92.3% in the 12 to <18 age group, 75.0% in the 18 to <65 years age group, and 87.5% in the ≥65 years age group. In the overall population, pragmatic seizure freedom rates at 12 months were 36.2% (all seizures), 34.1% (all focal seizures), and 45.5% (GTCS); the responder rate at 12 months was 64.4% in the overall population. In total, 52.7% of PWE experienced TEAEs, and 12.1% discontinued due to TEAEs. No significant changes were identified from baseline to 12 months in QOLIE-10, ESS, and the age-corrected EpiTrack and EpiTrack Junior scores.

Conclusion: PER was efficacious for focal and generalized seizures across all age groups and was generally well-tolerated, as demonstrated by the high retention rates at 12 months.

Keywords: epilepsy; first add-on; focal epilepsy; generalized epilepsy; perampanel; real-world.

Figure 1

Study design. ^aBased on the treating physician’s clinical judgment, patients who had seizures while receiving one other ASM as monotherapy. The decision to prescribe perampanel was made before and independently of the physician’s decision to include the patient in the study. ^bIf the patient withdrew from the study or discontinued perampanel treatment, the assessments of the final visit were collected (if part of routine clinical practice), and the reason for early termination was recorded. ASM, antiseizure medication, PER, perampanel; TEAE, treatment-emergent adverse event.

Figure 2

Patient disposition. *Primary reason for discontinuation. AE, adverse event; PER perampanel.

Figure 3

Kaplan–Meier plots of retention over 12 months: (A) overall population, (B) subgroups of PWE aged 12 to <18, ≥18 to <65, and ≥ 65 years, (C) by syndrome, (D) by seizure type, (E) by most common ASM monotherapy at baseline, (F) by MoA of baseline ASMs monotherapy, (G) by inducer status, and (H) by number of previous monotherapies. ASM, antiseizure medication; GTCS, generalized tonic–clonic seizures; JME, juvenile myoclonic epilepsy; MoA, mechanism of action; PER, perampanel.