Efficacy and safety of extended-release oxcarbazepine (Oxtellar XR™) as adjunctive therapy in patients with refractory partial-onset seizures: A randomized controlled trial Article uri icon

abstract

  • Objective: To evaluate the efficacy, tolerability, and safety of once-daily 1200 mg and 2400 mg SPN-804 (Oxtellar XR™, Supernus Pharmaceuticals), an extended-release tablet formulation of oxcarbazepine (OXC), added to 1-3 concomitant antiepileptic drugs (AEDs) in adults with refractory partial-onset seizures, with or without secondary generalization. Methods: The Prospective, Randomized Study of OXC XR in Subjects with Partial Epilepsy Refractory (PROSPER) study was a multinational, randomized, double-blind, parallel-group Phase 3 study. The primary efficacy endpoint was median percent reduction from baseline in monthly (28-day) seizure frequency for the 16-week double-blind treatment period in the intent-to-treat (ITT) population with analyzable seizure data. Other efficacy analyses included proportion of patients with ≥ 50%25 seizure reduction, proportion of patients seizure free, and the relationship between clinical response and plasma concentration. Results: Median percent reduction was -28.7%25 for placebo, -38.2%25 (P = 0.08 vs placebo) for once-daily SPN-804 1200 mg, and -42.9%25 (P = 0.003) for SPN-804 2400 mg. Responder rates were 28.1%25, 36.1%25 (P = 0.08), and 40.7%25 (P = 0.02); 16-week seizure-free rates in a pragmatic ITT analysis were 3.3%25, 4.9%25 (P = 0.59), and 11.4%25 (P = 0.008), respectively. When data were analyzed separately for study site clusters, a post hoc analysis demonstrated that both SPN-804 dosages were significantly superior to placebo in median percent seizure reduction (placebo: -13.3%25; 1200 mg: -34.5%25, P = 0.02; 2400 mg: -52.7%25, P = 0.006) in the North American study site cluster. A concentration-response analysis also supported a clinically meaningful effect for 1200 mg. Adverse event types reflected the drug%27s established profile. Adverse event frequency was consistent with a pharmacokinetic profile in which SPN-804 produces lower peak plasma concentrations vs immediate-release OXC. Once-daily dosing was not associated with any new safety signals. Conclusions: Adjunctive once-daily SPN-804 improved seizure control in patients with inadequately controlled partial-onset seizures. Adverse event occurrence and discontinuations due to adverse events suggest improved tolerability vs previously published data with immediate-release OXC. © 2013 The Authors.
  • Objective: To evaluate the efficacy, tolerability, and safety of once-daily 1200 mg and 2400 mg SPN-804 (Oxtellar XR™, Supernus Pharmaceuticals), an extended-release tablet formulation of oxcarbazepine (OXC), added to 1-3 concomitant antiepileptic drugs (AEDs) in adults with refractory partial-onset seizures, with or without secondary generalization. Methods: The Prospective, Randomized Study of OXC XR in Subjects with Partial Epilepsy Refractory (PROSPER) study was a multinational, randomized, double-blind, parallel-group Phase 3 study. The primary efficacy endpoint was median percent reduction from baseline in monthly (28-day) seizure frequency for the 16-week double-blind treatment period in the intent-to-treat (ITT) population with analyzable seizure data. Other efficacy analyses included proportion of patients with ≥ 50%25 seizure reduction, proportion of patients seizure free, and the relationship between clinical response and plasma concentration. Results: Median percent reduction was -28.7%25 for placebo, -38.2%25 (P = 0.08 vs placebo) for once-daily SPN-804 1200 mg, and -42.9%25 (P = 0.003) for SPN-804 2400 mg. Responder rates were 28.1%25, 36.1%25 (P = 0.08), and 40.7%25 (P = 0.02); 16-week seizure-free rates in a pragmatic ITT analysis were 3.3%25, 4.9%25 (P = 0.59), and 11.4%25 (P = 0.008), respectively. When data were analyzed separately for study site clusters, a post hoc analysis demonstrated that both SPN-804 dosages were significantly superior to placebo in median percent seizure reduction (placebo: -13.3%25; 1200 mg: -34.5%25, P = 0.02; 2400 mg: -52.7%25, P = 0.006) in the North American study site cluster. A concentration-response analysis also supported a clinically meaningful effect for 1200 mg. Adverse event types reflected the drug's established profile. Adverse event frequency was consistent with a pharmacokinetic profile in which SPN-804 produces lower peak plasma concentrations vs immediate-release OXC. Once-daily dosing was not associated with any new safety signals. Conclusions: Adjunctive once-daily SPN-804 improved seizure control in patients with inadequately controlled partial-onset seizures. Adverse event occurrence and discontinuations due to adverse events suggest improved tolerability vs previously published data with immediate-release OXC. © 2013 The Authors.

authors

publication date

  • 2014-01-01