Lacosamide cardiac safety: clinical trials in patients with partial-onset seizures.
OBJECTIVE
To evaluate the cardiac safety of adjunctive lacosamide in a large pool of adults with partial-onset seizures (POS).


METHODS
Post-randomization changes from baseline for electrocardiographic (ECG) measurements, diagnostic findings, and relevant adverse events (AEs) were compared for pooled data from three randomized, placebo-controlled trials of adjunctive lacosamide for the treatment of POS.


RESULTS
Lacosamide did not prolong the QTc interval or affect heart rate as determined by an analysis of data from patients randomized to lacosamide 200, 400, or 600 mg/day (n = 944) compared with placebo (n = 364). After 12-week maintenance treatment, mean changes from baseline for QRS duration were similar between the placebo and lacosamide 200 and 400 mg/day groups (0.0, -0.2, and 0.4 ms), but slightly increased for lacosamide 600 mg/day (2.3 ms). A small, dose-related mean increase in PR interval was observed (-0.3, 1.4, 4.4, and 6.6 ms for the placebo and lacosamide 200, 400, and 600 mg/day groups, respectively). First-degree atrioventricular (AV) block was reported as a non-serious AE in 0.0%, 0.7%, 0.2%, and 0.5% of patients in the same respective groups. Second- or higher degree AV block was not observed. There was no evidence of a PR-interval-related pharmacodynamic interaction of lacosamide with either carbamazepine or lamotrigine.


CONCLUSIONS
Evaluation of the pooled cardiac safety data from patients with POS showed that adjunctive lacosamide at the maximum recommended dose (400 mg/day) was not clearly associated with any cardiac effect other than a small, dose-related increase in PR interval that had no evident symptomatic consequence.
G D
GD
Rudd
Department of Cardiology, Campus Virchow Clinic, Charite'-University Medicine Berlin, Berlin, Germany.
W
W
Haverkamp
Cardiology Division, Department of Medicine, University of Utah, Salt Lake City, UT, USA.
J W
JW
Mason
Wenger Consulting, Durham, NC, USA.
T
T
Wenger
RAPID Pharmaceuticals, Rockville, MD, USA.
G
G
Jay
UCB Pharma, Raleigh, NC, USA.
D
D
Hebert
UCB Pharma, Raleigh, NC, USA.
P
P
Doty
Consulting Early Development, Bonn, Germany.
R
R
Horstmann
D000081:Acetamides / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000284:Administration, Oral; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004828:Epilepsies, Partial / Q000188:drug therapy; D005260:Female; D006339:Heart Rate; D006801:Humans; D000078334:Lacosamide; D008297:Male; D008875:Middle Aged
D000081:Acetamides; D000927:Anticonvulsants; D000078334:Lacosamide
PR interval; cardiac safety; electrocardiographic intervals; lacosamide; partial seizures