Multi-centric Phase III, single-arm, open-label clinical study to assess clinical safety, tolerability, and efficacy of intravenous lacosamide in focal onset seizures

Abstract

Background: In hospitalized seizure patients and during clinical seizure emergencies, parenteral administration of antiepileptic therapy (AED) is primary treatment modality. Appropriate selection and administration of AED is essential for immediate seizure control. The purpose of this study was to evaluate the safety, tolerability, and efficacy of lacosamide injection in adult patients with focal onset seizures (FOS) with or without secondary generalized tonic-clonic seizures or focal to bilateral tonic-clonic seizures. Methods: In this Phase 3 study, we enrolled 60 patients (≥18 years) with FOS and maintained on stable doses of oral lacosamide. Patients were switched to intravenous (i.v.) lacosamide (10 mg/ml); daily i.v. dosage and frequency were kept equivalent to oral lacosamide per patient. Lacosamide was infused intravenously over for 30 to 60 minutes at 12 hourly intervals for five consecutive days. Primary outcome was evaluating the safety and secondary outcome included measuring the seizure frequency during the treatment (day 1- 5) and at follow-up (day 12). Results: All patients enrolled completed the study. No significant changes in vital signs, or laboratory parameters, were observed at the end of treatment or follow-up when compared to baseline. The frequency analysis for all the components of electrocardiogram (ECG) was within the normal limits at all times. There were no serious adverse events (AEs) reported in this study. Overall, 26.66% of patients had mild to moderate AE intensity that resolved spontaneously without any other intervention. Most common AEs (frequency=5%) were abdominal pain upper, injection site pruritus, and nausea. The anti-seizure activity for lacosamide was maintained despite oral to i.v. switch of lacosamide. Conclusions: The study showed that i.v. lacosamide is a safe and effective strategy in patients with FOS and can be co-administered with other anti-epileptic drugs (AEDs), especially in acute settings with primary generalized tonic-clonic seizures. Registration: CTRI (CTRI/2011/07/001888; 14th July 2011).