Table 2

Analyses of time to second PGTCS during 24-week treatment period (FAS)

	Placebo			Lacosamide*			HR† (95% CI)
	N	No of events	KM survival estimate, %	N	No of events	KM survival estimate, %	HR† (95% CI)
All patients‡	121	76§	33.37	118	49¶	55.27	0.540 (0.377 to 0.774); p<0.001
Age group**
Paediatric (<18 years)	25	14	41.54	24	9	61.03	0.650 (0.271 to 1.561)
Adult (≥18 years)	96	62	31.25	94	40	53.60	0.527 (0.354 to 0.786)
Baseline PGTCS frequency††
≤2 per 28 days	95	56	37.45	93	34	60.31	0.501 (0.327 to 0.767)
>2 per 28 days	26	20	17.72	25	15	37.59	0.653 (0.334 to 1.277)
No of concomitant AEDs at trial entry‡
1	44	22	44.77	34	12	63.22	0.570 (0.279 to 1.165)
2	55	37	30.24	61	26	53.72	0.539 (0.323 to 0.900)
≥3	22	17	19.39	22	11	44.43	0.440 (0.201 to 0.965)
No of lifetime AEDs‡‡‡
1	28	15	37.56	21	9	55.56	0.578 (0.243 to 1.375)
2	54	34	35.35	46	14	66.33	0.374 (0.194 to 0.723)
≥3	39	27	28.28	52	26	45.04	0.574 (0.333 to 0.988)
SCB use at trial entry‡§§
Yes	46	37	17.36	46	22	45.88	0.428 (0.248 to 0.739)
No	75	39	43.39	72	27	60.80	0.630 (0.385 to 1.032)
Valproate use at trial entry‡
Yes	67	38	40.78	59	20	62.59	0.475 (0.276 to 0.819)
No	54	38	24.10	59	29	48.09	0.595 (0.364 to 0.972)
Levetiracetam use at trial entry‡
Yes	48	31	31.09	53	24	52.77	0.641 (0.373 to 1.101)
No	73	45	34.97	65	25	57.31	0.497 (0.304 to 0.812)

*One patient in the lacosamide group was randomised after the 125th event and does not appear in this analysis.
†HR <1 indicates time to second PGTCS was improved for lacosamide compared with placebo.
‡Comparison of lacosamide versus placebo was based on a Cox proportional hazards regression model with an effect for treatment, stratifying for the following combinations of patients’ baseline PGTCS frequency and age group: ≤2 PGTCS per 28 days in the combined baseline period and paediatric; ≤2 PGTCS per 28 days in the combined baseline period and adult; >2 PGTCS per 28 days in the combined baseline period.
§Of these events, 45 occurred during the titration period (by day 42) and 61 during the first 12 weeks of the treatment period (by day 84).
¶Of these events, 29 occurred during the titration period (by day 42) and 38 during the first 12 weeks of the treatment period (by day 84).
**Comparison based on a Cox proportional hazards regression model with an effect for treatment, stratifying for baseline PGTCS frequency: ≤2 PGTCS and >2 PGTCS per 28 days in the combined baseline period.
††Comparison based on a Cox proportional hazards regression model with an effect for treatment, stratifying for age group in the group with ≤2 PGTCS per 28 days in the combined baseline and with no stratification in the group with >2 PGTCS per 28 days.
‡‡AEDs stopped before or ongoing at lacosamide initiation.
§§SCB AEDs used in this trial were: carbamazepine, oxcarbazepine, phenytoin and lamotrigine.
AED, antiepileptic drug; FAS, full analysis set; KM, Kaplan-Meier; PGTCS, primary generalised tonic-clonic seizure; SCB, sodium channel blocking AED.