Table 3.

Parameter estimates of the final seizure model

Parameter	Description	Estimate	90% CIa
λ1 (1/day)b	λ for the time to 1st event	0.000733	0.000534	0.000957
p1	Weibull shape parameter 1st event	0.493	0.464	0.531
λ2 (1/day)b	λ for the 2nd + event	0.00889	0.00606	0.013
p2	Weibull shape parameter 2nd + event	0.713	0.675	0.75
NSP3M (<2) ~ λ1	Effect of NSP3M <2 on ln(λ1)	−1.12	−1.65	−0.648
NSP3M (7–50) ~ λ1	Effect of NSP3M 7–50 on ln(λ1)	1.94	1.43	2.43
NSP3M (>50) ~ λ1	Effect of NSP3M >50 on ln(λ1)	3.3	2.08	5.07
NSP3M (<2) ~ λ2	Effect of NSP3M <2 on ln(λ2)	−1.37	−2.06	−0.659
NSP3M (7–50) ~ λ2	Effect of NSP3M 7–50 on ln(λ2)	1.36	0.898	1.82
NSP3M (>50) ~ λ2	Effect of NSP3M >50 on ln(λ2)	2.53	1.98	3.1
AUC_LCM ~ λ1c	Slope of AUC-ln(λ1) for LCM 1st event	−0.00917	−0.0164	−0.000334
AUC_CBZ ~ λ1c	Slope of AUC-ln(λ1) for CBZ 1st event	−0.00658	−0.015	0.00325
AUC_LCM ~ λ2c	Slope of AUC-ln(λ1) for LCM 2nd + event	−0.00751	−0.00985	−0.006
AUC_CBZ ~ λ2c	Slope of AUC-ln(λ1) for CBZ 2nd + event	−0.0153	−0.0183	−0.0122
AGE ~ λ1d	Slope of AGE-ln(λ1) for LCM only	−0.0256	−0.0449	−0.0112
IIV ln(λ2) (SD)	Inter-individual variability ln(λ2)	2.03	1.85	2.2

AUC area under the plasma concentration–time curve over one dosing interval, CI confidence interval, CBZ carbamazepine, LCM lacosamide, NSP3M number of seizures in the 3 months before the trial, SD standard deviation

^a5th–95th percentiles of 500 bootstrap replicates

^bParameter back-transformed to normal scale as exp(x)

^cAUC centered on typical value at the first dose level (LCM 104 mg·h/L; CBZ 132 mg·h/L)

^dAGE centered on 41 years