Abstracts

Rationale: The long-term safety and tolerability of pregabalin in children with partial onset seizures has not been evaluated. Methods: This was a 12 month, open label extension of study A0081074 (NCT00437281), an 8-day safety, tolerability and pharmacokinetic study of pregabalin in children aged 1 month to 16 years with refractory partial seizures. Children had a minimum body weight of 3.5kg, seizures classified as simple partial, complex partial, or partial becoming secondarily generalized, and were eligible if they completed study A0081074. Eligibility of children who participated in but did not complete study A0081074 was considered on a case by case basis. Consent/assent was obtained from the parent/guardian as well as from each child if feasible. Children entered the study on the dose of pregabalin administered during study A0081074 (2.5, 5, 10 or 15mg/kg/day). Doses remained fixed for 1 month, after which dosing was flexible (2.5, 5, 7.5, 10 or 15mg/kg/day), based on tolerability. Dose levels were restricted until that dose had been studied in A0081074, with lower doses studied first. Pregabalin was administered as liquid or capsules depending on age and dose. The safety population consisted of all children who took ≥1 dose of study medication. ClinicalTrial.gov identifier: NCT00448916. Results: 54 children entered the current study, 53 of whom completed study A0081074, and 1 who discontinued that study prior to completion. The age range was 0.33-16.99 years. 29 (53.7%) children completed and 25 (46.3%) discontinued from the study; 9 (16.7%) discontinued due to AEs and 8 (14.8%) were no longer willing to participate. 16 (29.6%), 19 (35.2%) and 21 (38.9%) children took doses of 2.5, 5 and 10mg/kg/day, respectively, at any time. Only 9 (16.7%) children took a dose of 15mg/kg/day at any time because the use of higher doses was restricted by the study design, and in study A0081074 this dose was deemed not sufficiently tolerated for further evaluation in children aged >7 years. All 54 children were analyzed for safety. 47 (87.0%) children had treatment emergent AEs, typically of mild or moderate severity. 12 (22.2%) children had a SAE; 11 (20.4%) of the children with a SAE were aged ≤6 years. One child had a SAE of status epilepticus. No SAE was considered treatment related. No deaths were reported. The most frequently reported AEs (all causality) were pyrexia (15 children; 27.8%), upper respiratory tract infection (11; 20.4%) and convulsion (9; 16.7%). Somnolence was reported in 4 (7.4%) children and dizziness in 2 (3.7%). Conclusions: Pregabalin at doses up to and including 10mg/kg/day displayed good long-term safety and tolerability in children with partial seizures aged 1 month to 16 years, with no unexpected findings. The dose of 15mg/kg/day was taken by few children, in part due to study design. The AE profile was typical for the pediatric population and may appear to differ from that seen in adults, with dizziness and somnolence observed less commonly than in adult studies.