التفاصيل البيبلوغرافية
| العنوان: |
Using the drug repositioning approach to develop a novel therapy, tipepidine hibenzate sustained-release tablet (TS-141), for children and adolescents with attention-deficit/hyperactivity disorder |
| المؤلفون: |
Takuya Saito, Yushiro Yamashita, Akemi Tomoda, Takashi Okada, Hideo Umeuchi, Saki Iwamori, Satoru Shinoda, Akiko Mizuno-Yasuhira, Hidetoshi Urano, Izumi Nishino, Kazuhiko Saito |
| المصدر: |
BMC Psychiatry, Vol 20, Iss 1, Pp 1-12 (2020) |
| بيانات النشر: |
BMC, 2020. |
| سنة النشر: |
2020 |
| المجموعة: |
LCC:Psychiatry |
| مصطلحات موضوعية: |
Drug repositioning, TS-141, ADHD, CYP2D6 polymorphism, Phenotype, Clinical trial, Psychiatry, RC435-571 |
| الوصف: |
Abstract Background Asverin® (tipepidine hibenzate) has been used as an antitussive for > 50 years in Japan. Studies revealed that tipepidine modulates monoamine levels, by inhibiting G-protein-activated inwardly rectifying potassium (GIRK) channels, expecting the potential therapeutic effects of tipepidine for attention-deficit/hyperactivity disorder (ADHD) in recent years. In this study, TS-141, a sustained-release tablet of tipepidine, was developed for the treatment of ADHD through a drug repositioning approach. Methods The sustained-release profile of TS-141 in healthy adults was investigated, and tipepidine exposure in the plasma after the TS-141 administration was compared to that of Asverin in the phase I study. Phase II study was conducted to examine the effects of TS-141 30 (once a day), 60 (once a day), 120 mg (60 mg twice a day), or placebo, that is within the exposure in the maximum dosage of Asverin, in children and adolescents with ADHD, and was designed as an 8-week treatment, randomized, parallel group, double-blind, placebo-controlled trial recruiting 6–17-year-old children and adolescents diagnosed with ADHD. A total of 216 patients were randomized according to the CYP2D6 phenotype. The primary end-point was ADHD Rating Scale IV-J changes. Furthermore, effects of CYP2D6 phenotype on the efficacy in the subgroup analysis were investigated. Results TS-141 had the sustained-release profile, and the CYP2D6 phenotype had effects on the plasma exposure of tipepidine. ADHD RS-IV-J scores in all TS-141 dosages decreased from their baseline scores; however, no significant difference was observed in ADHD RS-IV-J score changes between the placebo and TS-141-administered groups. In patients with intermediate metabolizer CYP2D6, ADHD RS-IV-J score changes in the 120 mg group tended to be larger than that in the placebo group. Conclusions ADHD RS-IV-J changes on TS-141 may depend on the interaction between the TS-141 dose and CYP2D6 phenotype, suggesting that further clinical trials should be conducted with careful consideration of polymorphism. Drug repositioning approach of TS-141 was attempted at the same dose as that of antitussive; however, dose setting according to the indication was necessary. Trial registration Phase I study: JapicCTI-205235 (Registered 25 March 2020), Phase II study: JapicCTI-163244 (Registered 9 May 2016), https://www.clinicaltrials.jp/cti-user/trial/Show.jsp |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
1471-244X |
| Relation: |
http://link.springer.com/article/10.1186/s12888-020-02932-2; https://doaj.org/toc/1471-244X |
| DOI: |
10.1186/s12888-020-02932-2 |
| URL الوصول: |
https://doaj.org/article/770419312d724d3f834510d3df448818 |
| رقم الانضمام: |
edsdoj.770419312d724d3f834510d3df448818 |
| قاعدة البيانات: |
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