(566) PROVE Study 506: Analysis of a Retrospective, Phase IV Study of Perampanel in Real-World Clinical Care of Patients Based on Study Site Participation in Previous Clinical Trials
owner Idaho Comprehensive Epilepsy Center, Boise, ID, USA Boise, Idaho
Rationale: In the U.S., perampanel is approved for partial-onset seizures (adjunctive and monotherapy) in patients aged ≥ 4 years, and adjunctive treatment of primary generalized tonic-clonic seizures in patients aged ≥ 12 years. Epilepsy centers involved in previous clinical trials gain experience using perampanel in their patients. Here we assess differences in outcomes between centers involved in perampanel Phase III clinical trials vs those not involved. Data presented are based on the Phase IV, retrospective PROVE study. Methods: PROVE (Study 506; NCT03208660) was conducted between April 10, 2017 and April 1, 2019. Data were obtained from medical records of eligible patients who initiated perampanel treatment after January 1, 2014. Primary endpoint was retention rate (proportion of patients remaining on perampanel at 12, 18, and 24 months following treatment initiation; Safety Analysis Set [SAS]). Dosing experience, efficacy, and safety were secondary objectives. Outcomes were stratified by site type (trial vs. nontrial). Results: SAS included 1,703 patients (trial: n=427, mean [standard deviation (SD)] age, 24.6 [16.1] years; nontrial: n=1276, mean [SD] age, 29.8 [16.4] years). Majority of patients received 1–2 (trial: 29.7%, n=127/427; nontrial: 26.2%, n=334/1276) and 3–5 (trial: 20.4%, n=87/427; nontrial: 20.1%, n=256/1276) prior anti-seizure medications. Discontinuation rates were 47.8% (trial, n=204/427) and 47.6% (nontrial, n=608/1276). Primary reasons for discontinuation were adverse events (26.7%, trial; 21.6%, nontrial); inadequate therapeutic effect (16.6% trial; 12.1% nontrial); and patient choice (2.1%, trial; 3.9%, nontrial). Mean (SD) maximum doses were 7.0. (3.1) and 6.5 (3.2) mg/day for trial and nontrial, respectively. Titration schedules are shown in Table 1. Retention rates at 24 months were 54.7% (trial; n=133/243) and 46.1% (nontrial; n=368/799). In the full analysis set at Months 22-24 (trial, n=17/129; nontrial, n=34/200), median reductions in total seizure frequency/28 days were 66.7% and 95.0%, respectively; 50% responder rates were 64.7% (trial, n=11/17) and 82.4% (nontrial, n=28/34). Throughout the treatment period, treatment-emergent adverse events (TEAEs) occurred in 52.2% (trial, n=223/427) and 37.7% (nontrial, n=481/1276); most common were dizziness (11.5% vs 6.0%), aggression (6.1% vs 5.0%), irritability (5.2% vs 3.7%), and fatigue (4.0% vs 2.9%). Conclusions: Retention rates after 24 months were higher at trial vs nontrial sites which may reflect experience gained by sites involved in previous perampanel clinical trials. Efficacy was observed across both groups. Titration every two weeks was more common in trial vs nontrial sites suggesting trial sites had experience with slower titration. A greater incidence of TEAEs was reported at trial vs. nontrial sites potentially due to increased monitoring of AEs in clinical trials. Differences in patient numbers at trial and nontrial sites (427 vs. 1,276) should be considered when interpreting these data. Funding: Please list any funding that was received in support of this abstract.:
