Clobazam
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Clobazam In Patients with Lennox–Gastaut Syndrome Lily P. H. Yang • Lesley J. Scott
Published online: 29 September 2012 Springer International Publishing Switzerland 2012
Abstract Clobazam, as with other benzodiazepines, has a long history of use in the treatment of epilepsy. More recently, it was approved in the USA as adjunctive therapy for the treatment of seizures associated with Lennox–Gastaut syndrome in patients aged C2 years. In the pivotal, placebo-controlled CONTAIN trial in paediatric and adult patients with Lennox–Gastaut syndrome (n = 217 evaluable), adjunctive therapy with clobazam 5–40 mg/day for 12 weeks significantly reduced mean weekly drop seizure rates from baseline compared with adjunctive placebo (primary endpoint), with a significant dosage-dependent improvement in these rates. Results from a dosage-ranging, double-blind, multi-centre, phase II trial add further support for the efficacy of clobazam in paediatric and adult patients with Lennox–Gastaut syndrome (n = 61 evaluable). Improvements in mean weekly drop seizure rates with adjunctive clobazam treatment in these short-term trials was maintained in an ongoing, open-label extension study, with a 91.6 % reduction in mean weekly drop seizure rates from baseline (at randomization in the initial trials) to 24 months in the overall population. Treatment with
The manuscript was reviewed by: G.K. Bergey, Department of Neurology, John Hopkins Epilepsy Center, John Hopkins University School of Medicine, Baltimore, Maryland, USA; Y-T. Ng, University of Oklahoma Health Sciences Center, Department of Neurology, Oklahoma City, Oklahoma, USA; D. Schmidt, Epilepsy Research Group Berlin, Berlin, Germany. L. P. H. Yang L. J. Scott (&) Adis, 41 Centorian Drive, Mairangi Bay, North Shore, Private Bag 65901, 0754 Auckland, New Zealand e-mail: [email protected]
Key features and properties of clobazam (OnfiTM; FrisiumTM; UrbanolTM) Featured indication As adjunctive therapy for treating seizures associated with Lennox–Gastaut syndrome in patients aged C2 years Mechanism of action Thought to involve the potentiation of GABAergic neurotransmission, as a result of binding to the benzodiazepine site of the GABAA receptor Dosage and administration Starting dosage
5 mg once or twice daily, based on weight
Maintenance dosage
10 or 20 mg twice daily, based on weight
Route of administration
Oral
Pharmacokinetic profile of clobazam and its major active metabolite N-desmethylclobazam (N-CLB) in healthy adults receiving clobazam 40 mg once daily for 15 days Clobazam
N-CLB
1,373
2,566
2.0
7.0
Mean area under the plasma concentration–time curve from time zero to infinity (ngh/mL)
51,911
110,123
Mean elimination half-life (h)
32
57
Mean maximum serum concentration [Cmax] (ng/mL) Median time to Cmax (h)
Most common adverse events (incidence ‡10 %) Somnolence, pyrexia, upper respiratory tract infection, lethargy
adjunctive clobazam was generally well tolerated in these clinical trials and after at least 2 years of treatment in an open-la
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