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Abstract
Objective: To evaluate efficacy and safety of clobazam, a 1,5-benzodiazepine, as adjunctive therapy for Lennox-Gastaut syndrome (LGS).
Methods: Patients aged 2–60 years were randomized to placebo or clobazam 0.25, 0.5, or 1.0 mg/kg/day. Study consisted of 4-week baseline, 3-week titration, and 12-week maintenance phases, followed by a 2- or 3-week taper or continuation in an open-label extension. Primary endpoint was percentage decrease in mean weekly drop seizure rates during maintenance vs baseline phases for modified intention-to-treat (mITT) population. Secondary outcomes included other seizure types, responder rates, and physicians' and caregivers' global assessments.
Results: A total of 305 patients were screened, 238 were randomized, and 217 composed the mITT population. Of patients enrolled after a protocol amendment, 125/157 (79.6%) completed. Average weekly drop seizure rates decreased 12.1% for placebo vs 41.2% (p = 0.0120), 49.4% (p = 0.0015), and 68.3% (p < 0.0001) for the clobazam 0.25-, 0.5-, and 1.0-mg/kg/day groups. Responder rates (≥50%) were 31.6% (placebo) vs 43.4% (p = 0.3383), 58.6% (p = 0.0159), and 77.6% (p < 0.0001) for clobazam 0.25-, 0.5-, and 1.0-mg/kg/day groups. Physicians' and caregivers' assessments indicated clobazam significantly improved symptoms. Somnolence, pyrexia, upper respiratory infections, and lethargy were the most frequent adverse events reported for clobazam.
Conclusions: Clobazam significantly decreased weekly drop seizure rates in LGS. No new safety signals were identified.
Classification of evidence: This study provides Class II evidence that clobazam as adjunctive therapy is efficacious, in a dosage-dependent manner, in reducing mean weekly drop seizure rates of patients with LGS over 12 weeks.
Footnotes
Study funding: This study was funded by Lundbeck Inc. (Deerfield, IL). Manuscript preparation, including editing and formatting the manuscript, incorporating author comments, preparing tables and figures, and coordinating submission requirements, was provided by Robin L. Stromberg, PhD, of JK Associates, Inc. (Conshohocken, PA), and Michael A. Nissen, ELS, of Lundbeck Inc. This support was funded by Lundbeck.
Supplemental data at www.neurology.org.
-
- AE=
- adverse event;
- CI=
- confidence interval;
- GERD=
- gastroesophageal reflux disease;
- LGS=
- Lennox-Gastaut syndrome;
- mITT=
- modified intention-to-treat;
- OLE=
- open-label extension;
- OR=
- odds ratio;
- SAE=
- serious adverse event
- Received February 18, 2011.
- Accepted July 6, 2011.
- Copyright © 2011 by AAN Enterprises, Inc.
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