A randomized, open-label, multicenter comparative trial of levetiracetam and topiramate as adjunctive treatment for patients with focal epilepsy in Korea.

Abstract

OBJECTIVE:

The objective of this trial was to compare the effectiveness of levetiracetam (LEV) and topiramate (TPM) as adjunctive treatment for patients with focal seizures in Korea.

METHODS:

In this Phase IV, open-label, multicenter trial (NCT01229735), adults were randomized to treatment with LEV (1000-3000 mg/day) or TPM (200-400 mg/day). Only patients achieving LEV ≥1000 mg/day or TPM ≥100 mg/day after a 4-week up-titration entered the 20-week dose-finding and subsequent 28-week maintenance periods. The primary outcome was the 52-week retention rate; others included safety and exploratory efficacy outcomes.

RESULTS:

Of 343 randomized patients (LEV 177; TPM 166), 211 (61.5%) completed the trial. In the full analysis set (FAS), retention rate was 59.1% with LEV vs 56.6% with TPM (p = 0.7007), while in the prespecified sensitivity analysis, based on data from patients who received drug doses in the recommended range (LEV 176; TPM 113), it was 59.1% with LEV vs 42.5% with TPM (p = 0.0086). In the FAS, median percent reduction in seizure frequency from baseline was 74.47% with LEV and 67.86% with TPM (p = 0.0665); ≥50% responder rate was 69.0% vs 64.8% (p = 0.4205), and the 6-month seizure-freedom rate was 35.8% vs 22.3% (p = 0.0061). In the sensitivity analysis, differences between groups were greater, favoring LEV. Incidences of treatment-emergent adverse events (TEAEs) were 70.6% with LEV vs 77.1% with TPM; most frequently somnolence (20.3%), dizziness (18.1%), and nasopharyngitis (13.6%) with LEV; and decreased appetite (15.7%), dizziness (14.5%), and headache (14.5%) with TPM. Discontinuations due to TEAEs were 7.9% with LEV and 12.7% with TPM.

CONCLUSIONS:

In this open-label trial, the 52-week retention rate was not significantly different between LEV and TPM. However, LEV was associated with a substantially higher seizure freedom rate and a more favorable safety profile than TPM in this population of Korean patients with focal seizures.

• Authors: Sang Kun Lee, Sang Ahm Lee, Dong Wook Kim, Christian Loesch, Barbara Pelgrims, Toru Osakabe, Byungin Lee, N01353 study group
• Journal: Epilepsy & behavior : E&B (Epilepsy Behav) Vol. 97 Pg. 67-74 (08 2019) ISSN: 1525-5069 [Electronic] United States
• PMID: 31195326 (Publication Type: Clinical Trial, Phase IV, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019. Published by Elsevier Inc.

Chemical References

• Anticonvulsants
• Topiramate
• Levetiracetam

Topics

• Adult
• Anticonvulsants (adverse effects, therapeutic use)
• Dizziness (chemically induced)
• Drug Administration Schedule
• Drug Therapy, Combination
• Epilepsies, Partial (drug therapy)
• Female
• Headache (chemically induced)
• Humans
• Levetiracetam (adverse effects, therapeutic use)
• Male
• Middle Aged
• Republic of Korea
• Seizures (drug therapy)
• Sleepiness
• Topiramate (adverse effects, therapeutic use)