Phase 4 ELEVATE Study


Trevor J. Resnick, MD, reviews the ELEVATE Study 410 using perampanel as monotherapy or first adjunctive therapy in patients aged 4 years and older with partial-onset or primary generalized tonic-clonic seizures.

Trevor J. Resnick, MD: The abstracts that are being reviewed are descriptive and provide real-world data that are important for the care of patients. When looking at randomized, double-blind studies, which were done in a very rigid, robust fashion, they are not necessarily the way some treat patients in practice, but they provide a foundation and a framework for how to approach the use of those medications.

The real-world data with the subsequent descriptive studies provide important nuances on dosing, special populations, comorbidities, and dose escalation that are not part of the double-blind pivotal studies. 

The first study is a phase 4 study of perampanel as monotherapy or first adjunctive therapy in patients aged 4 years and above, with partial-onset or primary generalized tonic-clonic seizures. The first author on that abstract was [Vineet] Punia, [MD, MS].

The rationale for the abstract was that perampanel is approved for the treatment of partial-onset seizures, both as adjunctive and monotherapy in patients aged 4 years and above, as well as adjunctive therapy for primary generalized tonic-clonic seizures in patients above the age of 12.

Study 410, or ELEVATE, because it’s an ongoing, multicenter, open-label, phase 4 study, is the first prospective study of perampanel administered as monotherapy, or first adjunctive therapy in patients aged 4 years and above with all these different kinds of seizures: partial onset, with or without secondary generalization, and primary generalized seizures. This abstract is an update on the demographics and the initial results from patients enrolled in the study. From a titration standpoint—and this is different from the way it was done in the pivotal study—the patients were initiated with 2 mg per day, and they were uptitrated by 2 mg based upon clinical response and tolerability, which is more than the way we do in clinical practice.

The patients could receive a maximum of 12 mg per day depending upon their need for additional efficacy, and under those circumstances the dose would be titrated up. In general, the dosing was titrated every 2 weeks, but for those patients who were on enzyme-inducing medications, the uptitration could occur on a weekly basis. The primary end point was the retention rate at 3, 6, 9, and 12 months, respectively, and the secondary end points included safety and seizure freedom.

Unfortunately, when the abstract was submitted for publication, the data were available for only 13 patients. There’s not much takeaway because of the small N [number of patients] in the study. But some of the takeaway points that can be talked about are that no patients discontinued during the study, the mean age of the patients was 45 years, and the compliance rates were high, around 90% in the study. 

One takeaway is that, even though the N is low, with this titration schedule the compliance rate ended up being high, and that has occurred even though the treatment-emergent adverse events were present in 11 out of 13 of the patients enrolled in the study. But none of these adverse events led to study withdrawal. This is an interesting point because in many of these patients, the treatment adverse events are during the escalation period and they do resolve. Also, because these weren’t the kinds of patients who get enrolled in the pivotal studies, which tend to be patients who have intractable seizures and are on multiple medications, these patients were given perampanel either as monotherapy or first adjunctive therapy, so they tend to be more drug naïve and more sensitive to adverse events.

Unfortunately the study is ongoing. The N, or the number of patients, in the study was small. The only real takeaway that we can talk about is that the compliance rate was high and that the perampanel was well tolerated. Hopefully, there will be more information as the enrollment increases and we have a better way to assess the effectiveness of the medication compliance, the adverse events, and the dosing.

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