A team of researchers evaluated the potential development of tolerance to adjunctive clobazam in eligible patients enrolled in the open-label extension study OV-1004, which lasted until clobazam became available in the United States or for a maximum of 2 years outside the United States.
Study patients were initiated at clobazam 0.5mg/kg/day (max 40mg/day); doses were adjusted up to 2mg/kg/day (max 80mg/day) based on efficacy and tolerability. Mean dosages and drop-seizure rates for the first 2 years of the open-label extension of OV-1004 based on responder rates and baseline seizure quartiles in the Phase 3 lead-in Study OV-1012 were evaluated in post-hoc analyses (n=200). Also, separate patient listings were reviewed for dosage increases ≥40% and increasing seizure rates (defined as tolerance).
Findings from the analysis showed that for patients free of drop seizures, no notable change in dosage over 2 years was seen. For responders still showing drop seizures, dosages were increased. Weekly drop-seizure rates for 100% and ≥75% responders showed a consistent response over time. The analysis found that a few patients had a dosage increase ≥40% associated with an increase in seizure rates.
In general, increases in dosage may be the best strategy to attain seizure freedom. The authors added, “it is possible that the clinical development of tolerance to clobazam has been overstated.”
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