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

Yushi Inoue, Yoko Ohtsuka, Hiroko Ikeda, Harumi Yoshinaga, Katsuhiro Kobayashi, Jun Tohyama, Hiroshi Baba, Takateru Ishitsu, Chizuru Nishizato, Makiko Osawa, Yasuhiro Suzuki, Yoshihiro Takeuchi, Hitoshi Osaka, Yoshihiro Maegaki, Masaya Kubota, Tateki Fujiwara, Tatsuya Ogino

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31 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)725-731
Number of pages7
JournalEpilepsy Research
Volume108
Issue number4
DOIs
Publication statusPublished - May 2014

Keywords

  • Dravet syndrome
  • Efficacy
  • Pharmacokinetics
  • Stiripentol
  • Tolerability

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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    Inoue, Y., Ohtsuka, Y., Ikeda, H., Yoshinaga, H., Kobayashi, K., Tohyama, J., Baba, H., Ishitsu, T., Nishizato, C., Osawa, M., Suzuki, Y., Takeuchi, Y., Osaka, H., Maegaki, Y., Kubota, M., Fujiwara, T., & Ogino, T. (2014). Effectiveness of add-on stiripentol to clobazam and valproate in Japanese patients with Dravet syndrome: Additional supportive evidence. Epilepsy Research, 108(4), 725-731. https://doi.org/10.1016/j.eplepsyres.2014.02.008