Carisbamate Add-On May Lessen Partial-Onset Seizures

Allison Gandey

December 06, 2009

December 6, 2009 (Boston, Massachusetts) — New efficacy and safety data suggest carisbamate is effective at 18 months with minimal cognitive and psychiatric adverse events. Investigators presenting here at the American Epilepsy Society 63rd Annual Scientific Conference suggest that the experimental drug may offer an alternative for highly refractory patients with partial-onset seizures.

"It was very well tolerated," lead investigator Susan Lippmann, MD, from the Comprehensive Epilepsy Care Center for Children and Adults in Chesterfield, Missouri, said during an interview. "We did see some dizziness and unsteadiness in patients — as we would expect with any central nervous system drug — so this was not surprising."

Dr. Susan Lippmann

The proposed trade name for the Johnson & Johnson product is Comfyde. Its mechanism of action is unknown.

A phase 3 efficacy and safety study of carisbamate was recently suspended. A November 5 update on ClinicalTrials.gov said that enrollment has been temporarily suspended while changes are made to the protocol and consent form regarding drug hypersensitivity.

In the present analysis, investigators conducted an open-label extension of an earlier double-blind randomized trial. The study included 420 patients who had not responded to 3 or more antiepileptic drugs. Only about half of these patients (216) completed 18 months of treatment.

Patients were 18 to 70 years of age and had epilepsy for more than a year. Their partial-onset seizures were frequent, with 3 or more per 28 days during the prospective baseline phase of the study.

In the open-label intent-to-treat data — the only numbers provided in the poster presentation — investigators report efficacy in the 40% range.

"The efficacy was quite good," second author William Rosenfeld, MD, also from the Comprehensive Epilepsy Care Center, said during an interview. "We also did not see any major drug-drug interactions."

Table 1. Percentage of Reduction in Partial-Onset Seizure Frequency

Treatment Period, mo Reduction, %
1 – 6 37.3
1 – 12 40.0
1 – 18 42.7
Dr. William Rosenfeld

The researchers report that 2.9% of patients remained seizure free during the last 6 months of treatment.

Just more than 30% of patients had headaches while taking carisbamate. Another 15% experienced dizziness. About 10% had nasopharyngitis, somnolence, nausea, or vertigo. Insomnia was also a problem for some patients (5%). Some also developed flu and bronchitis (5%)

Psychiatric adverse events occurred in 13% of patients. The most common were anxiety and depression.

There were also 3 deaths. The investigators suggest that these were epilepsy related and not due to the study drug.

When asked by Medscape Neurology to comment on the study, Meriem Bensalem-Owen, MD, from the University of Kentucky in Lexington, said she is concerned about the number of deaths. "It is possible these were due to sudden unexplained death in epilepsy, but I don't think we should be quick to overlook these."

Dr. Bensalem-Owen said she would have liked to see these featured more prominently in the poster presentation as well.

Most patients received a dose of more than 400 to 800 mg/day. "There were very few outliers in the higher dose range," senior author Gerald Novak, MD, from Johnson & Johnson in Raritan, New Jersey, pointed out during an interview.

Table 2. Doses of Carisbamate in the Open-Label Extension Study

Dose, mg/day Patients, %
>400 – 800 59.7
<400 18.4
>800 – 1200 15.5
>1200 6.4

"Clearly not everyone is going to need a higher dose," Dr. Rosenfeld added. "But it's nice that we have the option to go up, if needed," he said.

Johnson & Johnson submitted a new drug application for carisbamate in 2008. To date, the US Food and Drug Administration has not granted marketing approval.

This study was funded by Johnson & Johnson. Dr. Novak is an employee of the company.

American Epilepsy Society (AES) 63rd Annual Scientific Conference: Poster 1.134. Presented December 5, 2009.

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