(565) Effect of Concomitant Anti-Seizure Medications (ASMs) During Long-Term (52 weeks) Adjunctive Perampanel Treatment in Japanese Pediatric Patients (Aged 4–<12 Years): Post Hoc Analysis of Study 311
Rationale: In the U.S. 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. Study 311 (NCT02849626) was a multicenter, open-label, single-arm study of perampanel oral suspension in pediatric patients (aged 4–< 12 years) with POS (with/without secondarily generalized seizures [SGS]) or PGTCS. In Japan, only patients with POS were enrolled. This post hoc analysis reports safety and efficacy data by concomitant baseline ASM use in Study 311 in Japanese pediatric patients with POS, with/without SGS. Methods: Patients completing the 27-week Core Study (4-week Pretreatment; 23-week Treatment [11-week Titration; 12-week Maintenance]) could enter Extension A (29-week Maintenance; 4-week Follow-up). Patients were taking 1–3 concomitant ASMs at baseline and during the Core Study. This post hoc analysis assessed safety and efficacy by number and most common concomitant ASMs received during baseline. Safety assessments included monitoring treatment-emergent adverse events (TEAEs). Efficacy assessments for POS and SGS included median percent change in seizure frequency/28 days from baseline and 50% responder rates. Cumulative data from all enrolled patients are included. Results: Overall, 65 Japanese patients were enrolled in the Core Study and 53 entered Extension A. Of all 65 patients, seven (10.8%) patients received one ASM during baseline and 29 (44.6%) patients each received two or three ASMs. The most common concomitant ASMs during baseline were valproic acid (n=26 [40.0%]), levetiracetam (n=23 [35.4%]), lamotrigine (n=21 [32.3%]), clobazam (n=20 [30.8%]), topiramate (n=11 [16.9%]), and the enzyme-inducing ASM carbamazepine (n=10 [15.4%]); patients could receive >1 of these ASMs. An overview of TEAEs by concomitant ASM use is shown in Table 1; the most common TEAEs varied but nasopharyngitis, somnolence, and influenza were common in all groups. Median percent reductions in seizure frequency/28 days during Weeks 1–13 and 40–52 are shown in Figures 1A–B. During Weeks 40–52, 50% responder rates for total POS and SGS by number of baseline ASMs were: 1 ASM: 50.0% (n=2/4) and 66.7% (n=2/3); 2 ASMs: 65.2% (n=15/23) and 83.3% (n=10/12); and 3 ASMs: 43.5% (n=10/23) and 70.0% (n=7/10), respectively. For the most common concomitant ASMs, 50% responder rates were: valproic acid: 47.6% (n=10/21) and 60.0% (n=6/10); levetiracetam: 62.5% (n=10/16) and 83.3% (n=5/6); lamotrigine: 46.7% (n=7/15) and 66.7% (n=4/6); clobazam: 53.3% (n=8/15) and 66.7% (n=6/9); topiramate: 60.0% (n=6/10) and 100.0% (n=6/6); and carbamazepine: 57.1% (n=4/7) and 100.0% (n=1/1), respectively. Conclusions: Consistent with the overall population, these data suggest long-term adjunctive perampanel is generally well tolerated and seizure control is sustained for up to 52 weeks in Japanese pediatric patients with POS (with/without SGS), irrespective of baseline ASM use. Funding: Please list any funding that was received in support of this abstract.:
