Abstracts

Rationale: Population pharmacokinetic (PK) analysis in epilepsy patients on 1-3 background antiepileptic drugs (AEDs) showed reductions in lacosamide (LCM) plasma concentrations when LCM was coadministered with potent enzyme inducing AEDs (EIAEDs). The purpose of this analysis was to assess LCM plasma concentration and tolerability during conversion from LCM add-on therapy (adjunctive to either one EIAED or one non-EIAED [NEIAED]) to LCM monotherapy. Methods: Patients on one background AED enrolled in the double-blind, historical-controlled, conversion to LCM monotherapy trial (SP902; NCT00520741) were included in the analysis. The study consisted of 3-week LCM Titration (add-on to the background AED), 6-week background AED Withdrawal and 10-week LCM Monotherapy Phases. Patients who provided plasma samples during both LCM add-on (2 weeks after LCM initiation) and LCM monotherapy (6 weeks after complete withdrawal of the background AED) were included in the PK analysis. LCM tolerability profile was assessed during the 3-study phases in the safety population. PK and tolerability analyses were performed by CYP class of the background AED (EIAED [CBZ, PHT]; NEIAED [LEV, LTG, PGB, GBP, ZNS, CLN, VPA, TPM, OXC]). Results: In patients discontinuing NEIAEDs (n=72), LCM trough plasma concentration and clearance were similar during LCM monotherapy and add-on therapy (Figure 1). In patients discontinuing EIAED (n=25), LCM trough plasma concentration increased by 27% and LCM clearance decreased by 21% during LCM monotherapy versus add-on therapy. Six weeks after complete withdrawal of the background EIAED, LCM plasma concentration and clearance were similar to that in patients withdrawn from NEIAEDs. In patients on a background EIAED, no increase in the incidence of TEAEs and TEAEs leading to discontinuation was observed during the 10-week LCM Monotherapy Phase versus the 3-week LCM Titration Phase (Table 1). During the LCM Monotherapy Phase, the overall incidence and type of the most frequently reported TEAEs and TEAEs leading to discontinuation were generally similar in patients withdrawn from EIAEDs and NEIAEDs. Conclusions: The data from this post-hoc analysis of the conversion to LCM monotherapy trial in adults on one background AED suggested that the observed increase in LCM plasma concentration after withdrawal of a background EIAED did not result in worsening of the LCM tolerability profile. Exposure of LCM under monotherapy is identical in patients converted from LCM add-on therapy with either one EIAED or one NEIAED. Funding: UCB Pharma-sponsored.