Abstracts

Rationale: The elderly population is the most rapidly growing segment in more developed countries and incidence of epilepsy is increasing at older ages. The number of elderly patients included into the adjunctive lacosamide (LCM) pivotal epilepsy trials is limited due to upper age limits in the inclusion criteria. Given that elderly with epilepsy are usually treated with AED monotherapy, tolerability data on the use of LCM monotherapy in elderly would be most informative for clinical practice. Therefore, safety and tolerability of LCM monotherapy in elderly enrolled in the placebo-controlled trials in diabetic neuropathic pain (DNP; discontinued development program) were analyzed. Methods: Data from 5 double-blind, placebo-controlled trials (NCT00861445, NCT00235469, NCT00238524, NCT00135109 and NCT00350103) were pooled including 1500 patients with DNP treated with either placebo or LCM monotherapy doses up to 400 mg/day. Of these patients 411 (27.4%) were elderly (≥65 years). Safety data of the elderly were compared (1) to data of the younger patients (<65 years) within the same trials and (2) to data from pivotal epilepsy trials with similar LCM dosing schedules in patients treated with either placebo or LCM adjunctive therapy up to 400 mg/day (n=1105 of whom 17 (1.5%) ≥65 years). Overall, the DNP population was older and at higher cardiovascular risk due to age and their underlying diabetes. Results: In the DNP population, the most frequently reported adverse events (AEs) for the monotherapy LCM 200 and 400 mg/day doses combined, in the elderly versus younger patients were dizziness (11.7% vs 9.4%), nausea (9.1% vs 7.1%) and headache (7.0% vs 8.1%). Although incidences of Cardiac Disorders AEs appear slightly higher in the elderly vs younger patients in the placebo (6.2% vs 3.9%), LCM 200mg/day (4.8% vs 3.3%) and 400mg/day groups (7.0% vs 4.1%), there was no difference between the LCM and the corresponding placebo groups. In patients on 200mg/day LCM the incidence of discontinuations due to any AE or due to dizziness were similar between age groups (Table 1). Within the pivotal epilepsy trials, corresponding common AEs for adjunctive LCM 200 and 400 mg/day doses combined were dizziness (24.6%), headache (12.8%) and nausea (9.9%). Incidences of Cardiac Disorders AEs were 1.4% (placebo), 2.2% (LCM 200mg/day) and 2.8% (400mg/day) (Table 2). Conclusions: LCM monotherapy up to 400 mg/day was well tolerated in elderly with DNP. The discontinuation rates due to any AE or to dizziness in patients on 200mg/day LCM were similar between elderly (≥65 years) and younger (<65 years) patients. Overall, the AE profile was comparable to the known observations from the epilepsy trials. Dizziness rates on LCM monotherapy were lower than when LCM was added to other anti-epileptic drugs. This data is significant for the use of LCM in the elderly population in that it is indicating that incidence and type of AEs are comparable to younger adults and no age specific safety signal was noted. Funded by UCB Pharma