Effectiveness of add-on stiripentol to clobazam and valproate in Japanese patients with Dravet syndrome: additional supportive evidence.

Abstract

PURPOSE:

To evaluate the efficacy and safety of stiripentol as add-on therapy in Japanese patients with Dravet syndrome treated with clobazam (CLB) and valproate (VPA).

METHODS:

In this open-label study, patients aged 1-30 years entered a 4-week baseline phase, followed by a 4-week stiripentol dose-adjustment and 12-week fixed-dose phase. The primary efficacy endpoint was responder rate (proportion of patients with a ≥50% reduction from baseline phase in clonic or tonic-clonic seizure frequency over the last 4 weeks of fixed-dose treatment [target phase]). Safety and pharmacokinetics were also assessed.

KEY FINDINGS:

Of 27 patients screened in the baseline phase, 24 patients entered the dose-adjustment phase. All patients completed the study. Responder rate was 66.7% (16/24, 95% CI: 44.7-84.4%), and four patients became free from clonic or tonic-clonic seizures. The duration of clonic or tonic-clonic seizures was also significantly reduced in the target versus baseline phase. The most frequent adverse events were somnolence, anorexia, ataxia, nasopharyngitis and γ-glutamyl transpeptidase increase, all of which were of mild-to-moderate severity. Stiripentol plasma concentration in the fixed-dose phase was 4-25 μg/mL. After adding stiripentol to CLB and VPA, the minimum plasma concentrations of CLB and N-desmethyl-CLB (NCLB) increased and that of 4'-hydroxy-N-desmethyl-CLB(OH-NCLB) decreased, while those of VPA and bromide (optionally used) were not affected.

SIGNIFICANCE:

Add-on stiripentol to CLB and VPA was well tolerated and significantly decreased clonic or tonic-clonic seizures in patients with Dravet syndrome.

• Authors: Yushi Inoue, Yoko Ohtsuka, STP-1 Study Group
• Journal: Epilepsy research (Epilepsy Res) Vol. 108 Issue 4 Pg. 725-31 (May 2014) ISSN: 1872-6844 [Electronic] Netherlands
• PMID: 24630050 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Anticonvulsants
• Dioxolanes
• Benzodiazepines
• Clobazam
• Valproic Acid
• stiripentol

Topics

• Adolescent
• Adult
• Anticonvulsants (administration & dosage, adverse effects, therapeutic use)
• Asian People
• Benzodiazepines (administration & dosage, adverse effects, therapeutic use)
• Child
• Child, Preschool
• Clobazam
• Dioxolanes (administration & dosage, adverse effects, therapeutic use)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Drug Therapy, Combination
• Epilepsies, Myoclonic (drug therapy)
• Female
• Humans
• Infant
• Japan
• Male
• Treatment Outcome
• Valproic Acid (administration & dosage, adverse effects, therapeutic use)
• Young Adult