دورية أكاديمية
An Exposure-Response Analysis of the Clinical Efficacy of Ponesimod in a Randomized Phase II Study in Patients with Multiple Sclerosis.
| العنوان: | An Exposure-Response Analysis of the Clinical Efficacy of Ponesimod in a Randomized Phase II Study in Patients with Multiple Sclerosis. |
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| المؤلفون: | Gisleskog PO; POG Pharmacometrics, London, UK., Valenzuela B; Janssen-Cilag Spain, part of Janssen Pharmaceutical Companies, Madrid, Spain., Scherz T; Actelion Pharmaceuticals Ltd, part of Janssen Pharmaceutical Companies, Allschwil, Switzerland., Burcklen M; Actelion Pharmaceuticals Ltd, part of Janssen Pharmaceutical Companies, Allschwil, Switzerland., Pérez-Ruixo JJ; Janssen-Cilag Spain, part of Janssen Pharmaceutical Companies, Madrid, Spain., Poggesi I; Janssen-Cilag Italy, part of Janssen Pharmaceutical Companies, Milan, Italy. ipoggesi@its.jnj.com. |
| المصدر: | Clinical pharmacokinetics [Clin Pharmacokinet] 2021 Sep; Vol. 60 (9), pp. 1227-1237. Date of Electronic Publication: 2021 Apr 29. |
| نوع المنشور: | Clinical Trial, Phase II; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Country of Publication: Switzerland NLM ID: 7606849 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1179-1926 (Electronic) Linking ISSN: 03125963 NLM ISO Abbreviation: Clin Pharmacokinet Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: [Switzerland] : Adis, part of Springer Science+Business Media Original Publication: New York, ADIS Press. |
| مواضيع طبية MeSH: | Multiple Sclerosis*/drug therapy , Multiple Sclerosis, Relapsing-Remitting*/diagnostic imaging , Multiple Sclerosis, Relapsing-Remitting*/drug therapy, Humans ; Infant ; Thiazoles ; Treatment Outcome |
| مستخلص: | Background and Objective: Ponesimod is a sphingosphine-1-phosphate receptor modulator being developed for the treatment of multiple sclerosis. The effects of disease-modifying treatments on magnetic resonance imaging (MRI) lesions in relapsing multiple sclerosis accurately predict effects on clinical relapses, therefore MRI lesion counts are generally accepted efficacy endpoints in phase II clinical studies of multiple sclerosis disease-modifying treatments. Here, we characterize the effect of ponesimod systemic exposure on the cumulative number of T1 gadolinium-enhancing (Gd+) lesions and the annualized relapse rate in a phase IIb study. Methods: This study assessed the cumulative number of new Gd+ lesions on T1-weighted MRI scans (primary endpoint) at weeks 12, 16, 20, and 24 and the annualized relapse rate (secondary endpoint). The effect of the demographic and prognostic covariates of sex, age, weight, T1 Gd+ lesions at baseline, and Expanded Disability Status Scale score at baseline were explored. Analyses were performed using NONMEM, Version 7.3.0 (ICON plc). Results: An increase in ponesimod exposure led to a statistically significant decrease in the cumulative T1 Gd+ lesions on MRI from week 12 to 24 of treatment. Increasing the ponesimod daily dose beyond 20 mg did not provide significant additional benefits. Sex, age, T1 Gd+ lesions at baseline, and Expanded Disability Status Scale score at baseline were associated with a higher number of new cumulative T1 Gd+ from week 12 to 24 of treatment. Conclusions: This analysis shows a relationship between ponesimod exposure and the cumulative number of new T1 Gd+ lesions. Sex, age, T1 Gd+ lesions at baseline, and Expanded Disability Status Score at baseline were not found to be importantly associated with the magnitude of ponesimod effect, and consequently, there is no indication from these analyses that dosage adjustments based on the explored covariates are warranted. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT01006265, registration date 1 November, 2009. (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.) |
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| سلسلة جزيئية: | ClinicalTrials.gov NCT01006265 |
| المشرفين على المادة: | 0 (Thiazoles) 5G7AKV2MKP (ponesimod) |
| تواريخ الأحداث: | Date Created: 20210429 Date Completed: 20211028 Latest Revision: 20220217 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1007/s40262-021-01020-2 |
| PMID: | 33914286 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1179-1926 |
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| DOI: | 10.1007/s40262-021-01020-2 |