Exposure–Response Modeling in Adults and Adolescents With Schizophrenia to Support the Extrapolation of Brexpiprazole Efficacy to Adolescents.
In order to accelerate drug development and avoid unnecessary drug trials in vulnerable pediatric populations, the US Food and Drug Administration (FDA) released a general advice letter to sponsors permitting the effectiveness of atypical antipsychotics for the treatment of schizophrenia in adults t...
| Publicado en: | Journal of Clinical Pharmacology Vol. 64; no. 10; pp. 1236 - 1246 |
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| Autores principales: | , , , , , |
| Formato: | equations & formulas research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
Oct2024
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=179962831&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 179962831 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00912700 5WH jtl: Journal of Clinical Pharmacology issn: 00912700 maglogo: Y pubinfo: dt: Oct2024 vid: 64 iid: 10 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 179962831 178291257 179962831 179962831 10.1002/jcph.2464 179962831 ppf: 1236 ppct: 10 formats: tig: atl: Exposure–Response Modeling in Adults and Adolescents With Schizophrenia to Support the Extrapolation of Brexpiprazole Efficacy to Adolescents. aug: au: Wang, Xiaofeng Gopalakrishnan, Mathangi Rich, Benjamin Gobburu, Jogarao V. Larsen, Frank Raoufinia, Arash affil: Otsuka Pharmaceutical Development & Commercialization Inc., Princeton NJ,, USA sug: subj: Schizophrenia Drug Therapy Schizophrenia Drug Therapy Schizophrenia Symptoms Antipsychotic Agents Therapeutic Use Aripiprazole Administration and Dosage Drug Efficacy Evaluation Drug Monitoring Human Adolescence Adult Quantitative Studies Dose-Response Relationship, Drug Scales Patient Dropouts Models, Theoretical Age of Onset United States Food and Drug Administration Treatment Outcomes Disease Attributes Dopamine Agents Serotonin Agents Funding Source Adolescent: 13-18 years Adult: 19-44 years ab: In order to accelerate drug development and avoid unnecessary drug trials in vulnerable pediatric populations, the US Food and Drug Administration (FDA) released a general advice letter to sponsors permitting the effectiveness of atypical antipsychotics for the treatment of schizophrenia in adults to be extrapolated to adolescents. Extrapolation is based on the evidence‐based assumptions that (1) disease characteristics and (2) response to therapy, are similar in adults and adolescents. Whereas the FDA validated the extrapolation approach using data from multiple drug development programs, aripiprazole data are the most relevant to confirm the validity of the extrapolation approach for brexpiprazole, since aripiprazole and brexpiprazole both modulate dopaminergic and serotonergic signaling in the brain. The aims of this analysis were (1) to quantitatively assess the aripiprazole exposure (average steady‐state concentration)–response (Positive and Negative Syndrome Scale total score change from baseline) similarity between adults and adolescents with schizophrenia, (2) to extend the aripiprazole exposure–response modeling to brexpiprazole using adult data, and (3) to use the brexpiprazole model to predict schizophrenia symptom response in adolescents. Disease–drug–dropout models were developed using patient‐level data from clinical studies of aripiprazole (1007 adults, 294 adolescents) and brexpiprazole (1235 adults) in schizophrenia. The aripiprazole model demonstrated similar exposure–response between adults and adolescents with schizophrenia, validating the extrapolation approach. Extrapolation of the brexpiprazole adult exposure–response model to adolescents predicted the efficacy of brexpiprazole in adolescents aged 13‐17 years with schizophrenia. pubtype: Academic Journal doctype: equations & formulas research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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