This randomized, double-blind, non-inferiority trial compared lacosamide monotherapy to carbamazepine-CR monotherapy for newly diagnosed epilepsy over 12 months. The primary endpoints were the proportion of patients seizure-free at 6 and 12 months and time to first seizure. Results showed that lacosamide was non-inferior to carbamazepine-CR for seizure freedom at both timepoints. Lacosamide was well-tolerated with fewer drug interactions and side effects than other antiepileptic drugs. The study establishes lacosamide as a suitable new option for epilepsy monotherapy.

1. Dr. Rahi Kiran
SR I
Department of Neurology
GMC, Kota.

2. This article was published on May 10,
2016 at NEJM.org.

3.  Monotherapy is preferred as first-line treatment of
patients with newly diagnosed epilepsy
 But most of the newest antiepileptic drugs are initially
licensed only for adjunctive use.
 Many factors restrict the number of drugs that will be
suitable for a given patient. So, additional drugs for
monotherapy are needed.

4.  Lacosamide is a third-generation antiepileptic drug
that was approved by FDA in 2008 as an adjunctive
treatment for patients with focal seizures.
 MOA : selectively enhancing slow inactivation of
voltage-gated sodium channels.
 carbamazepine-CR is used as a reference treatment
because its efficacy as first-line monotherapy for focal
epilepsy has been established.

5.  The US FDA - lacosamide as monotherapy in treating
partial-onset seizures > 17 years in sep 2014.
 loading dose of 200 mg (oral or injection) followed 12
hours later by a 100-mg bd, increase by 50 mg/wk upto
150-200mg bd.
 Adv – 100% BA, no enzyme induction, less protein
binding, no interaction,

6. Eligibility criteria
Age> 16 years with New or recently diagnosed epilepsy
with
• unprovoked focal seizures -simple partial [IA]
-complex partial [IB], or
-partial evolving to secondary
generalisation.
(according to the International Classifi cation of Epileptic Seizures, 1981)
 GTCS without signs of focal onset (with no history or clinical
or EEG findings of idiopathic generalised epilepsy. )

7. Eligibility criteria
 Additional criterion - at least two unprovoked seizures
separated by >48 h in the previous 12 months ( one had
occurred in the previous 3 months)
 An EEG and CT scan or MRI examination within the
previous 12 months.
 The use of benzodiazepines as a rescue therapy for epilepsy
was permitted if taken at a maximum frequency of once per
week.

8. Exclusion criteria
 status epilepticus,
 seizure types other than focal or GTCS(without focal origin),
 Conversion disorders,
 atrioventricular block or any other echocardiographic
abnormalities were excluded.
 Asian ancestry HLA-A*3101 or HLA-B*1502 alleles positive

9. Exclusion criteria
 previous treatment with lacosamide or carbamazepine
 treatment with any antiepileptic drug in the 6 months
before screening.
 Treatment with any drug or product (eg, grapefruit)
that might have affected carbamazepine-CR
metabolism

10. Trial Design
 phase 3
 Multicenter
 randomized,
 double-blind
 non-inferiority trial
 185 sites (specialist epilepsy or general neurology centres) in 29
countries in Europe, North America, and the Asia Pacific region.

11. Randomisation
 randomly assigned in a 1:1 ratio according to a
predetermined schedule generated by a software
application.
 stratified - no. of seizures in the 3-month period before
trial - < or > 2.
 All investigators, patients, and trial personnel were
unaware of treatment assignment.
 The trial medications and packaging were identical in size
and colour.

13. Primary end points
 proportion of patients remaining free from seizures
for 6 and 12 consecutive months after stabilisation at
the last assessed dose.
 the time to first seizure during 12 months of treatment
 time from the first dose of trial medication to with
drawl because of an adverse event or lack of efficacy.

14. safety and tolerability
 incidence of any treatment-emergent adverse
events,
 withdrawal due to treatment-emergent adverse events,

15. Statistical analysis
 full analysis and perprotocol sets (eg, missing seizure
data, poor adherence to the study drug, or intake of
prohibited medications).
 Prespecified subgroup analyses were done for - clear
diagnosis of focal epilepsy at the end of the treatment
period, those with a history of GTCS only (without
clear focal origin) and those aged 65 years or older at
trial entry.

16. Statistical analysis
 Kaplan-Meier method to estimate the proportions
of patients who would be free from seizures at 6
and 12 months after stabilisation while taking the
last assessed dose.

18. Baseline characteristics

19. Baseline characteristics

21. Results
 April 27, 2011 and Aug 7, 2015.

24. CONCLUSION
 Adv- less interaction, less side effects.
 Limitation – no placebo control
 levetiracetam and zonisamide approved as monotherapy
after comparing with carbamazepine CR only.
 Further studies are needed to compare lacosamide with
levetiracetam and zonisamide

25. Thank You