Academic Journal
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
| 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: | Directory of Open Access Journals |
Full Text Finder | ResultId |
1 |
|---|---|
| Header |
edsdoj Directory of Open Access Journals edsdoj.770419312d724d3f834510d3df448818 943 3 Academic Journal academicJournal 942.749328613281 |
| PLink |
https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&scope=site&db=edsdoj&AN=edsdoj.770419312d724d3f834510d3df448818&custid=s6537998&authtype=sso |
| FullText |
Array
(
[Availability] => 0
)
Array ( [0] => Array ( [Url] => https://doaj.org/article/770419312d724d3f834510d3df448818 [Name] => EDS - DOAJ [Category] => fullText [Text] => View record in DOAJ [MouseOverText] => View record in DOAJ ) [1] => Array ( [Url] => https://resolver.ebscohost.com/openurl?custid=s6537998&groupid=main&authtype=ip,guest&sid=EBSCO:edsdoj&genre=article&issn=1471244X&ISBN=&volume=20&issue=1&date=20201101&spage=1&pages=1-12&title=BMC Psychiatry&atitle=Using%20the%20drug%20repositioning%20approach%20to%20develop%20a%20novel%20therapy%2C%20tipepidine%20hibenzate%20sustained-release%20tablet%20%28TS-141%29%2C%20for%20children%20and%20adolescents%20with%20attention-deficit%2Fhyperactivity%20disorder&id=DOI:10.1186/s12888-020-02932-2 [Name] => Full Text Finder (s6537998api) [Category] => fullText [Text] => Full Text Finder [Icon] => https://imageserver.ebscohost.com/branding/images/FTF.gif [MouseOverText] => Full Text Finder ) ) |
| Items |
Array
(
[Name] => Title
[Label] => Title
[Group] => Ti
[Data] => 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
)
Array ( [Name] => Author [Label] => Authors [Group] => Au [Data] => <searchLink fieldCode="AR" term="%22Takuya+Saito%22">Takuya Saito</searchLink><br /><searchLink fieldCode="AR" term="%22Yushiro+Yamashita%22">Yushiro Yamashita</searchLink><br /><searchLink fieldCode="AR" term="%22Akemi+Tomoda%22">Akemi Tomoda</searchLink><br /><searchLink fieldCode="AR" term="%22Takashi+Okada%22">Takashi Okada</searchLink><br /><searchLink fieldCode="AR" term="%22Hideo+Umeuchi%22">Hideo Umeuchi</searchLink><br /><searchLink fieldCode="AR" term="%22Saki+Iwamori%22">Saki Iwamori</searchLink><br /><searchLink fieldCode="AR" term="%22Satoru+Shinoda%22">Satoru Shinoda</searchLink><br /><searchLink fieldCode="AR" term="%22Akiko+Mizuno-Yasuhira%22">Akiko Mizuno-Yasuhira</searchLink><br /><searchLink fieldCode="AR" term="%22Hidetoshi+Urano%22">Hidetoshi Urano</searchLink><br /><searchLink fieldCode="AR" term="%22Izumi+Nishino%22">Izumi Nishino</searchLink><br /><searchLink fieldCode="AR" term="%22Kazuhiko+Saito%22">Kazuhiko Saito</searchLink> ) Array ( [Name] => TitleSource [Label] => Source [Group] => Src [Data] => BMC Psychiatry, Vol 20, Iss 1, Pp 1-12 (2020) ) Array ( [Name] => Publisher [Label] => Publisher Information [Group] => PubInfo [Data] => BMC, 2020. ) Array ( [Name] => DatePubCY [Label] => Publication Year [Group] => Date [Data] => 2020 ) Array ( [Name] => Subset [Label] => Collection [Group] => HoldingsInfo [Data] => LCC:Psychiatry ) Array ( [Name] => Subject [Label] => Subject Terms [Group] => Su [Data] => <searchLink fieldCode="DE" term="%22Drug+repositioning%22">Drug repositioning</searchLink><br /><searchLink fieldCode="DE" term="%22TS-141%22">TS-141</searchLink><br /><searchLink fieldCode="DE" term="%22ADHD%22">ADHD</searchLink><br /><searchLink fieldCode="DE" term="%22CYP2D6+polymorphism%22">CYP2D6 polymorphism</searchLink><br /><searchLink fieldCode="DE" term="%22Phenotype%22">Phenotype</searchLink><br /><searchLink fieldCode="DE" term="%22Clinical+trial%22">Clinical trial</searchLink><br /><searchLink fieldCode="DE" term="%22Psychiatry%22">Psychiatry</searchLink><br /><searchLink fieldCode="DE" term="%22RC435-571%22">RC435-571</searchLink> ) Array ( [Name] => Abstract [Label] => Description [Group] => Ab [Data] => 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 ) Array ( [Name] => TypeDocument [Label] => Document Type [Group] => TypDoc [Data] => article ) Array ( [Name] => Format [Label] => File Description [Group] => SrcInfo [Data] => electronic resource ) Array ( [Name] => Language [Label] => Language [Group] => Lang [Data] => English ) Array ( [Name] => ISSN [Label] => ISSN [Group] => ISSN [Data] => 1471-244X ) Array ( [Name] => NoteTitleSource [Label] => Relation [Group] => SrcInfo [Data] => http://link.springer.com/article/10.1186/s12888-020-02932-2; https://doaj.org/toc/1471-244X ) Array ( [Name] => DOI [Label] => DOI [Group] => ID [Data] => 10.1186/s12888-020-02932-2 ) Array ( [Name] => URL [Label] => Access URL [Group] => URL [Data] => <link linkTarget="URL" linkTerm="https://doaj.org/article/770419312d724d3f834510d3df448818" linkWindow="_blank">https://doaj.org/article/770419312d724d3f834510d3df448818</link> ) Array ( [Name] => AN [Label] => Accession Number [Group] => ID [Data] => edsdoj.770419312d724d3f834510d3df448818 ) |
| RecordInfo |
Array
(
[BibEntity] => Array
(
[Identifiers] => Array
(
[0] => Array
(
[Type] => doi
[Value] => 10.1186/s12888-020-02932-2
)
)
[Languages] => Array
(
[0] => Array
(
[Text] => English
)
)
[PhysicalDescription] => Array
(
[Pagination] => Array
(
[PageCount] => 12
[StartPage] => 1
)
)
[Subjects] => Array
(
[0] => Array
(
[SubjectFull] => Drug repositioning
[Type] => general
)
[1] => Array
(
[SubjectFull] => TS-141
[Type] => general
)
[2] => Array
(
[SubjectFull] => ADHD
[Type] => general
)
[3] => Array
(
[SubjectFull] => CYP2D6 polymorphism
[Type] => general
)
[4] => Array
(
[SubjectFull] => Phenotype
[Type] => general
)
[5] => Array
(
[SubjectFull] => Clinical trial
[Type] => general
)
[6] => Array
(
[SubjectFull] => Psychiatry
[Type] => general
)
[7] => Array
(
[SubjectFull] => RC435-571
[Type] => general
)
)
[Titles] => Array
(
[0] => Array
(
[TitleFull] => 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
[Type] => main
)
)
)
[BibRelationships] => Array
(
[HasContributorRelationships] => Array
(
[0] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Takuya Saito
)
)
)
[1] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Yushiro Yamashita
)
)
)
[2] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Akemi Tomoda
)
)
)
[3] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Takashi Okada
)
)
)
[4] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Hideo Umeuchi
)
)
)
[5] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Saki Iwamori
)
)
)
[6] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Satoru Shinoda
)
)
)
[7] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Akiko Mizuno-Yasuhira
)
)
)
[8] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Hidetoshi Urano
)
)
)
[9] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Izumi Nishino
)
)
)
[10] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Kazuhiko Saito
)
)
)
)
[IsPartOfRelationships] => Array
(
[0] => Array
(
[BibEntity] => Array
(
[Dates] => Array
(
[0] => Array
(
[D] => 01
[M] => 11
[Type] => published
[Y] => 2020
)
)
[Identifiers] => Array
(
[0] => Array
(
[Type] => issn-print
[Value] => 1471244X
)
)
[Numbering] => Array
(
[0] => Array
(
[Type] => volume
[Value] => 20
)
[1] => Array
(
[Type] => issue
[Value] => 1
)
)
[Titles] => Array
(
[0] => Array
(
[TitleFull] => BMC Psychiatry
[Type] => main
)
)
)
)
)
)
)
|
| IllustrationInfo |