FULL-LENGTH ORIGINAL RESEARCH
Adjunctive levetiracetam in children, adolescents, and adults with primary generalized seizures: Open-label, noncomparative, multicenter, long-term follow-up study
Article first published online: 2 NOV 2011
Wiley Periodicals, Inc. © 2011 International League Against Epilepsy
Volume 53, Issue 1, pages 111–119, January 2012
How to Cite
Delanty, N., Jones, J. and Tonner, F. (2012), Adjunctive levetiracetam in children, adolescents, and adults with primary generalized seizures: Open-label, noncomparative, multicenter, long-term follow-up study. Epilepsia, 53: 111–119. doi: 10.1111/j.1528-1167.2011.03300.x
- Issue published online: 4 JAN 2012
- Article first published online: 2 NOV 2011
- Accepted September 7, 2011; Early View publication November 2, 2011.
- Clinical trial;
- Antiepileptic drugs;
- Absence seizures;
- Myoclonic seizures;
- Tonic–clonic seizures;
- Idiopathic generalized epilepsy
Purpose: To evaluate the long-term efficacy and tolerability of adjunctive levetiracetam (LEV) in patients with uncontrolled idiopathic generalized epilepsy (IGE).
Methods: This phase III, open-label, long-term, follow-up study (N167; NCT00150748) enrolled patients (4 to <65 years) with primary generalized seizures (tonic–clonic, myoclonic, absence). Patients received adjunctive LEV at individualized doses (1,000–4,000 mg/day; 20–80 mg/kg/day for children/adolescents weighing <50 kg). Efficacy results are reported for all seizure types [intention-to-treat (ITT) population, N = 217] and subpopulations with tonic–clonic (n = 152), myoclonic (n = 121), and/or absence (n = 70) seizures at baseline.
Key Findings: One hundred twenty-five (57.6%) of 217 patients were still receiving treatment at the end of the study. Mean (standard deviation, SD) LEV dose was 2,917.5 (562.9) mg/day. Median (Q1–Q3) exposure to LEV was 2.1 (1.5–2.8) years, and the maximum duration was 4.6 years. Most patients were taking one (124/217, 57.1%) or ≥2 (92/217, 42.4%) concomitant antiepileptic drugs (AEDs). Seizure freedom of ≥6 months (all seizure types; primary efficacy end point) was achieved by 122 (56.2%) of 217 patients, and 49 (22.6%) of 217 patients had complete seizure freedom. Seizure freedom of ≥6 months from tonic–clonic, myoclonic, and absence seizures was achieved by 95 (62.5%) of 152, 75 (62.0%) of 121, and 44 (62.9%) of 70 patients, respectively. Mean (SD) maximum seizure freedom duration was 371.7 (352.4) days. At least one treatment-emergent adverse event (TEAE) was reported by 165 (76%) of 217 patients; most TEAEs were mild/moderate in severity, with no indication of an increased incidence over time. Seventeen (7.8%) of 217 patients discontinued medication because of TEAEs. The most common psychiatric TEAEs were depression (16/217, 7.4%), insomnia (9/217, 4.1%), nervousness (8/217, 3.7%), and anxiety (7/217, 3.2%).
Significance: Adjunctive LEV (range 1,000–4,000 mg/day) demonstrated efficacy as a long-term treatment for primary generalized seizures in children, adolescents, and adults with IGE, and was well tolerated.