A post hoc analysis presented at the 2017 American Epilepsy Society (AES) annual meeting in Washington, DC, found that designating a new clinical trial endpoint can reduce the risk to participants. It also demonstrated that adjunctive perampanel doubles the reduction of seizures seen on standard therapy (abstract 3.263).

Tablets. (Source: Pixabay)

Studies that require some patients to take a placebo pose significant risk to patients with primary generalized tonic-clonic (PGTC) seizures, which a “time to event” endpoint can significantly reduce. In the “time to event” structure, patients may leave a study once the lack of efficacy of either the drug or placebo becomes evident.

In this study, the researchers enrolled 164 patients over age 12 who had idiopathic generalized epilepsy and uncontrolled PGTC seizures and randomized them 1:1 to receive placebo or adjunctive perampanel. Patients continued on the antiepileptic drugs they were already taking. In addition to a change in seizure frequency and responder rates, the researchers used time from first dose of perampanel to nth+1 seizure event as an endpoint. They defined the nth+1 as the baseline seizure frequency per 28 days +1.

Patients receiving perampanel saw a 76.5% reduction in seizure frequency per 28 days compared to 38.4% for those taking the placebo. Nearly two-thirds (64.2%) of participants in the perampanel arm were 50% responders compared to 39.5% of those receiving placebo. The median time to the nth+1 event was 43 days for those on placebo, but could not be estimated for those receiving perampanel as fewer than 50% of participants in that group had experienced any PGTC seizure events.

“The results suggest that time to the nth+1 seizure would be a useable endpoint in studies of PGTC seizures and should be considered for future trials,” the researchers concluded.