Evaluation of Probenecid Efficacy on Cluster Seizures During Anti-Seizure Medication Tapering in Presurgical Focal Epilepsy Video-EEG Monitoring

The primary objective is to evaluate the efficacy of probenecid in achieving the cessation of seizure recurrence in patients presenting with cluster seizures during the reduction of anti-seizure medication for pre-surgical video-EEG monitoring in individuals with focal epilepsy. 5

Secondary objectives include:

• The requirement for rescue treatment.
• The duration of seizure activity at 4, 6, and 12 hours post-administration.
• The occurrence of tonic-clonic generalised seizure or status epilepticus within 12 hours of treatment.
• The appearance of seizure-related lesion within 12 hours of treatment.
• Evaluation of interictal activity.
• The daily seizure frequency during the remaining monitoring period following the initial 12-hour post-treatment window.
• The impact on major vital signs from administration until 2 hours post-treatment.
• The incidence of adverse events and serious adverse events.

The sponsor did not provide information regarding the total number of participants. The study population consists of both male and female patients diagnosed with focal epilepsy. Eligible participants are between 6 and 50 years of age, with specific weight requirements of at least 20 kg for children and more than 50 kg for adults. The cohort includes individuals undergoing video-EEG monitoring in an Epilepsy Monitoring Unit for presurgical evaluation. Inclusion necessitates the planned withdrawal of anti-seizure medication to precipitate seizure occurrence or the management of epilepsy where seizures occur without dose reduction. Participants must be capable of administering oral therapy and must allow for recording lasting longer than 12 hours following the second seizure of a cluster seizure.

This phase 4 clinical trial is designed to evaluate the efficacy of probenecid in preventing the recurrence of cluster seizures in patients with focal epilepsy during anti-seizure medication reduction for presurgical video-EEG monitoring. The study involves the administration of either the test product or a placebo to individuals experiencing a seizure cluster, defined as at least two epileptic seizures lasting less than 10 minutes occurring within a 6-hour period. The primary endpoint is the proportion of patients remaining seizure-free between 60 minutes and 12 hours following administration. Secondary endpoints include the duration of seizures, the occurrence of status epilepticus, seizure-related injuries, and changes in interictal activity. Study participation begins with a screening process to ensure eligibility based on age, weight, and clinical requirements for hospital monitoring. Following the administration of the intervention, clinical assessment is conducted via video and EEG recordings. The study duration for recruitment is estimated to occur between October 2025 and November 2028.

The experimental medication is probenecid, administered as SANTURIL 500 mg scored tablets. The total daily dose is 3 grams, delivered via the oral route.

A placebo is utilized as a comparator treatment during the clinical trial.

The primary efficacy endpoint is the proportion of patients without seizures between 60 minutes and 12 hours following the administration of probenecid or placebo. This is evaluated in patients experiencing a seizure cluster, defined as at least two epileptic seizures lasting less than 10 minutes occurring within a 6-hour period, during presurgical hospital video-EEG monitoring for focal epilepsy. Assessments are performed by a neurologist using video and electroencephalogram recordings.

Secondary efficacy parameters include:

• The introduction of benzodiazepines or an increase in antiepileptic medication within 12 hours of administration.
• Total time spent in seizure, measured in minutes.
• The occurrence of tonic-clonic generalized seizure or status epilepticus.
• Incidence of seizure-related injury, such as bone or tooth fracture or hematoma.
• Changes in interictal activity, quantified by the evolution of the number of interictal spikes recorded during 15 minutes at 2 hours post-administration compared to the same period the previous day.
• The total number of seizures during the remaining duration of monitoring.
• Evolution of heart rate and blood pressure from administration to 2 hours post-administration.