Once-daily eslicarbazepine equals twice-daily carbamazepine for controlling partial-onset seizures

VANCOUVER – Once-daily eslicarbazepine may offer a more convenient option for controlling newly diagnosed partial-onset seizures, suggest findings of a phase III trial reported at the annual meeting of the American Academy of Neurology.

The study of 815 adult patients found that 71.1% of those treated with once-daily eslicarbazepine as monotherapy were seizure free for at least 6 months, compared with 75.6% of those treated with twice-daily controlled-release carbamazepine as monotherapy. The difference fell within the predefined margin for noninferiority.

Additionally, the safety profile of eslicarbazepine was at least as good as that of carbamazepine, and there were no new or unexpected adverse events, relative to those seen in trials in which the former has been used as adjunctive therapy.

“Eslicarbazepine has the same efficacy, has a little bit better safety, and it can be taken once a day,” coauthor Dr. Pedro André Kowacs commented in an interview. “I have been working with it for 12 years. It’s a very, very good drug.”

“There are few antiepileptic drugs that can be taken once a day,” he added. “We know that a more simple schedule enhances adherence of the patient, compliance of the patient to therapy.”

Also, patients can choose when to take eslicarbazepine, according to Dr. Kowacs, who is a neurologist at the Instituto de Neurologia de Curitiba in Brazil. “You can take it in the morning or you can take it at night. It doesn’t matter,” he elaborated. “This is in contrast to, say, phenobarbital. If you take it in the morning, perhaps you are going to sleep all day long. And if you take three tabs of Dilantin (phenytoin), probably you get a little bit dizzy.”

In the trial, patients were randomized evenly to once-daily eslicarbazepine (brand name Aptiom) or twice-daily controlled-release carbamazepine (brand name Tegretol XR), each as monotherapy. Eslicarbazepine is currently approved by the U.S. Food and Drug Administration for the treatment of partial-onset seizures as monotherapy or adjunctive therapy.

In both groups, the patients were treated according to a three-step dose-level design, with upward titration of dose if they experienced seizures. However, the majority in each group – 67.6% for eslicarbazepine and 76.9% for carbamazepine – remained at the lowest-dose level studied (800 mg once daily and 200 mg twice daily, respectively).

The primary endpoint was the proportion of patients in the per-protocol population who were seizure free for the entire 26-week evaluation period at the last received dose level.

Overall, that proportion was 71.1% in the eslicarbazepine group and 75.6% in the carbamazepine group, Dr. Kowacs reported in an Emerging Science session. The absolute difference of –4.28% and the lower bound of the 95% confidence interval of –10.30% fell within the predefined noninferiority margin of –12%.

The 1-year rate of freedom from seizures was 64.7% in the eslicarbazepine group and 70.3% in the carbamazepine group. The absolute difference of –5.46% and the lower bound of the 95% confidence interval of –11.88% again fell within the noninferiority margin.

Patients in the eslicarbazepine tended to have a lower rate of treatment-emergent adverse events possibly related to the drug, compared with counterparts in the carbamazepine group (41.1% vs. 49.5%). The most common were dizziness and headache.

“The [gamma glutamyl transferase level] was increased in more patients taking carbamazepine,” Dr. Kowacs noted, with a rate of 12.4% versus 2.7% with eslicarbazepine. “Hyponatremia occurred in both groups, but no patient was symptomatic.”

There were two deaths each in the eslicarbazepine group (from glioblastoma and cardiac arrest) and the carbamazepine group (from suicide and lung cancer).

Dr. Kowacs disclosed that he has received personal compensation for activities with Bial, Abbott Laboratories, GlaxoSmithKline, and Cyberonics. The trial was sponsored by Bial-Portela & Cª SA.

VANCOUVER – Once-daily eslicarbazepine may offer a more convenient option for controlling newly diagnosed partial-onset seizures, suggest findings of a phase III trial reported at the annual meeting of the American Academy of Neurology.

The study of 815 adult patients found that 71.1% of those treated with once-daily eslicarbazepine as monotherapy were seizure free for at least 6 months, compared with 75.6% of those treated with twice-daily controlled-release carbamazepine as monotherapy. The difference fell within the predefined margin for noninferiority.

Additionally, the safety profile of eslicarbazepine was at least as good as that of carbamazepine, and there were no new or unexpected adverse events, relative to those seen in trials in which the former has been used as adjunctive therapy.

“Eslicarbazepine has the same efficacy, has a little bit better safety, and it can be taken once a day,” coauthor Dr. Pedro André Kowacs commented in an interview. “I have been working with it for 12 years. It’s a very, very good drug.”

“There are few antiepileptic drugs that can be taken once a day,” he added. “We know that a more simple schedule enhances adherence of the patient, compliance of the patient to therapy.”

Also, patients can choose when to take eslicarbazepine, according to Dr. Kowacs, who is a neurologist at the Instituto de Neurologia de Curitiba in Brazil. “You can take it in the morning or you can take it at night. It doesn’t matter,” he elaborated. “This is in contrast to, say, phenobarbital. If you take it in the morning, perhaps you are going to sleep all day long. And if you take three tabs of Dilantin (phenytoin), probably you get a little bit dizzy.”

In the trial, patients were randomized evenly to once-daily eslicarbazepine (brand name Aptiom) or twice-daily controlled-release carbamazepine (brand name Tegretol XR), each as monotherapy. Eslicarbazepine is currently approved by the U.S. Food and Drug Administration for the treatment of partial-onset seizures as monotherapy or adjunctive therapy.

In both groups, the patients were treated according to a three-step dose-level design, with upward titration of dose if they experienced seizures. However, the majority in each group – 67.6% for eslicarbazepine and 76.9% for carbamazepine – remained at the lowest-dose level studied (800 mg once daily and 200 mg twice daily, respectively).

The primary endpoint was the proportion of patients in the per-protocol population who were seizure free for the entire 26-week evaluation period at the last received dose level.

Overall, that proportion was 71.1% in the eslicarbazepine group and 75.6% in the carbamazepine group, Dr. Kowacs reported in an Emerging Science session. The absolute difference of –4.28% and the lower bound of the 95% confidence interval of –10.30% fell within the predefined noninferiority margin of –12%.

The 1-year rate of freedom from seizures was 64.7% in the eslicarbazepine group and 70.3% in the carbamazepine group. The absolute difference of –5.46% and the lower bound of the 95% confidence interval of –11.88% again fell within the noninferiority margin.

Patients in the eslicarbazepine tended to have a lower rate of treatment-emergent adverse events possibly related to the drug, compared with counterparts in the carbamazepine group (41.1% vs. 49.5%). The most common were dizziness and headache.

“The [gamma glutamyl transferase level] was increased in more patients taking carbamazepine,” Dr. Kowacs noted, with a rate of 12.4% versus 2.7% with eslicarbazepine. “Hyponatremia occurred in both groups, but no patient was symptomatic.”

There were two deaths each in the eslicarbazepine group (from glioblastoma and cardiac arrest) and the carbamazepine group (from suicide and lung cancer).

Dr. Kowacs disclosed that he has received personal compensation for activities with Bial, Abbott Laboratories, GlaxoSmithKline, and Cyberonics. The trial was sponsored by Bial-Portela & Cª SA.

VANCOUVER – Once-daily eslicarbazepine may offer a more convenient option for controlling newly diagnosed partial-onset seizures, suggest findings of a phase III trial reported at the annual meeting of the American Academy of Neurology.

The study of 815 adult patients found that 71.1% of those treated with once-daily eslicarbazepine as monotherapy were seizure free for at least 6 months, compared with 75.6% of those treated with twice-daily controlled-release carbamazepine as monotherapy. The difference fell within the predefined margin for noninferiority.

Additionally, the safety profile of eslicarbazepine was at least as good as that of carbamazepine, and there were no new or unexpected adverse events, relative to those seen in trials in which the former has been used as adjunctive therapy.

“Eslicarbazepine has the same efficacy, has a little bit better safety, and it can be taken once a day,” coauthor Dr. Pedro André Kowacs commented in an interview. “I have been working with it for 12 years. It’s a very, very good drug.”

“There are few antiepileptic drugs that can be taken once a day,” he added. “We know that a more simple schedule enhances adherence of the patient, compliance of the patient to therapy.”

Also, patients can choose when to take eslicarbazepine, according to Dr. Kowacs, who is a neurologist at the Instituto de Neurologia de Curitiba in Brazil. “You can take it in the morning or you can take it at night. It doesn’t matter,” he elaborated. “This is in contrast to, say, phenobarbital. If you take it in the morning, perhaps you are going to sleep all day long. And if you take three tabs of Dilantin (phenytoin), probably you get a little bit dizzy.”

In the trial, patients were randomized evenly to once-daily eslicarbazepine (brand name Aptiom) or twice-daily controlled-release carbamazepine (brand name Tegretol XR), each as monotherapy. Eslicarbazepine is currently approved by the U.S. Food and Drug Administration for the treatment of partial-onset seizures as monotherapy or adjunctive therapy.

In both groups, the patients were treated according to a three-step dose-level design, with upward titration of dose if they experienced seizures. However, the majority in each group – 67.6% for eslicarbazepine and 76.9% for carbamazepine – remained at the lowest-dose level studied (800 mg once daily and 200 mg twice daily, respectively).

The primary endpoint was the proportion of patients in the per-protocol population who were seizure free for the entire 26-week evaluation period at the last received dose level.

Overall, that proportion was 71.1% in the eslicarbazepine group and 75.6% in the carbamazepine group, Dr. Kowacs reported in an Emerging Science session. The absolute difference of –4.28% and the lower bound of the 95% confidence interval of –10.30% fell within the predefined noninferiority margin of –12%.

The 1-year rate of freedom from seizures was 64.7% in the eslicarbazepine group and 70.3% in the carbamazepine group. The absolute difference of –5.46% and the lower bound of the 95% confidence interval of –11.88% again fell within the noninferiority margin.

Patients in the eslicarbazepine tended to have a lower rate of treatment-emergent adverse events possibly related to the drug, compared with counterparts in the carbamazepine group (41.1% vs. 49.5%). The most common were dizziness and headache.

“The [gamma glutamyl transferase level] was increased in more patients taking carbamazepine,” Dr. Kowacs noted, with a rate of 12.4% versus 2.7% with eslicarbazepine. “Hyponatremia occurred in both groups, but no patient was symptomatic.”

There were two deaths each in the eslicarbazepine group (from glioblastoma and cardiac arrest) and the carbamazepine group (from suicide and lung cancer).

Dr. Kowacs disclosed that he has received personal compensation for activities with Bial, Abbott Laboratories, GlaxoSmithKline, and Cyberonics. The trial was sponsored by Bial-Portela & Cª SA.