Evaluation of carisbamate, a novel antiepileptic drug, in photosensitive patients: an exploratory, placebo-controlled study.
OBJECTIVE
Carisbamate, a novel neuromodulatory agent with antiepileptic properties, was evaluated in patients with photoparoxysmal responses to intermittent photic stimulation (IPS) in this multicenter, non-randomized, single-blind, placebo-controlled, proof-of-concept study.


METHODS
Eighteen Caucasian patients (14 females, 4 males) with a mean age of 30 years (range: 16-51 years) underwent standardized IPS under three eye conditions (during eye closure, eyes closed and eyes open) at hourly intervals for up to 8h after receiving placebo (Day 1), carisbamate (Day 2) and placebo (Day 3). Carisbamate was given at single doses of 250-1000 mg. All patients received one or two concomitant antiepileptic drugs, most commonly valproate.


RESULTS
Carisbamate produced a dose-dependent reduction in photosensitivity in the 13 evaluable patients, with abolishment of photoparoxysmal responses in 3 patients and clinically significant suppression of such responses in 7 additional patients. Photosensitivity was abolished or reduced in all five patients in the 1000-mg dose group. The onset of carisbamate occurred rapidly, with clinically significant suppression achieved before or near the time peak plasma drug levels were reached. The duration of action was dose-related and long-lasting, with clinically significant reductions of photosensitivity observed for up to 32 h after doses of 750 or 1000 mg. Carisbamate was generally well tolerated, with dizziness and nausea reported more frequently after active drug than placebo.


CONCLUSIONS
This study shows that carisbamate exhibits dose-related antiepileptic effects in the photosensitivity model. Randomized, controlled studies of carisbamate in epilepsy patients inadequately controlled by their existing AED therapy are warranted.
Trenité
Dorothée G A Kasteleijn-Nolst
DG
University La Sapienza II, Via Vitorchiano 81, 00189 Roma, Italy. dkasteleijn@planet.nl <dkasteleijn@planet.nl>
French
Jacqueline A
JA
Hirsch
Edouard
E
Macher
Jean-Paul
JP
Meyer
Bernd-Ulrich
BU
Grosse
Pascal A
PA
Abou-Khalil
Bassel W
BW
Rosenfeld
William E
WE
van Gerven
Joop
J
Novak
Gerald P
GP
Parmeggiani
Lucio
L
Schmidt
Bernd
B
Gibson
David
D
Guerrini
Renzo
R
D000293:Adolescent; D000328:Adult; D000339:Affect / Q000187:drug effects; D000927:Anticonvulsants / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002219:Carbamates / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003863:Depression / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D020195:Epilepsy, Reflex / Q000188:drug therapy* / Q000523:psychology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010775:Photic Stimulation; D011569:Psychiatric Status Rating Scales
D000927:Anticonvulsants; D002219:Carbamates; C518914:S-2-O-carbamoyl-1-o-chlorophenyl-ethanol