Reldesemtiv in Patients with Spinal Muscular Atrophy: a Phase 2 Hypothesis-Generating Study
| العنوان: | Reldesemtiv in Patients with Spinal Muscular Atrophy: a Phase 2 Hypothesis-Generating Study |
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| المؤلفون: | John W. Day, Lisa Meng, Jean K. Mah, Bettina M. Cockroft, Andrew A. Wolff, Jenny Wei, Angela Genge, Anne M. Connolly, Ali Habib, Craig Campbell, Perry B. Shieh, Jeffrey Statland, Maryam Oskoui, Tina Duong, Carolina Tesi-Rocha, Basil T. Darras, Nicholas E. Johnson, Nancy L. Kuntz, Fady I. Malik, Stacy A. Rudnicki, Jinsy A. Andrews, Kevin Felice |
| المصدر: | Neurotherapeutics Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, vol 18, iss 2 Paediatrics Publications |
| بيانات النشر: | Springer International Publishing, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, Pyridines, Investigational, spinal muscular atrophy clinical trial, Cohort Studies, Medicine, Pharmacology (medical), Child, biology, six-minute walk test, Drugs, Skeletal, Pharmacology and Pharmaceutical Sciences, Middle Aged, SMA, Reldesemtiv, Muscular Atrophy, Quartile, 6.1 Pharmaceuticals, Cohort, Public Health and Health Services, Muscle, Female, Original Article, pharmacokinetics, Adult, medicine.medical_specialty, Spinal, Adolescent, Clinical Trials and Supportive Activities, Urology, Walk Test, Placebo, Muscular Atrophy, Spinal, Young Adult, Rare Diseases, Pharmacokinetics, Double-Blind Method, Clinical Research, pharmacodynamics, Humans, Pyrroles, Muscle, Skeletal, Aged, Pharmacology, Neurology & Neurosurgery, business.industry, Troponin I, Neurosciences, Correction, Spinal muscular atrophy, Drugs, Investigational, medicine.disease, Troponin, Pyrimidines, Pharmacodynamics, biology.protein, Neurology (clinical), business |
| الوصف: | This phase 2, double-blind, placebo-controlled, hypothesis-generating study evaluated the effects of oral reldesemtiv, a fast skeletal muscle troponin activator, in patients with spinal muscular atrophy (SMA). Patients ≥ 12 years of age with type II, III, or IV SMA were randomized into 2 sequential, ascending reldesemtiv dosing cohorts (cohort 1: 150 mg bid or placebo [2:1]; cohort 2: 450 mg bid or placebo [2:1]). The primary objective was to determine potential pharmacodynamic effects of reldesemtiv on 8 outcome measures in SMA, including 6-minute walk distance (6MWD) and maximum expiratory pressure (MEP). Changes from baseline to weeks 4 and 8 were determined. Pharmacokinetics and safety were also evaluated. Patients were randomized to reldesemtiv 150 mg, 450 mg, or placebo (24, 20, and 26, respectively). The change from baseline in 6MWD was greater for reldesemtiv 450 mg than for placebo at weeks 4 and 8 (least squares [LS] mean difference, 35.6 m [p = 0.0037] and 24.9 m [p = 0.058], respectively). Changes from baseline in MEP at week 8 on reldesemtiv 150 and 450 mg were significantly greater than those on placebo (LS mean differences, 11.7 [p = 0.038] and 13.2 cm H2O [p = 0.03], respectively). For 6MWD and MEP, significant changes from placebo were seen in the highest reldesemtiv peak plasma concentration quartile (Cmax > 3.29 μg/mL; LS mean differences, 43.3 m [p = 0.010] and 28.8 cm H2O [p = 0.0002], respectively). Both dose levels of reldesemtiv were well tolerated. Results suggest reldesemtiv may offer clinical benefit and support evaluation in larger SMA patient populations. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1878-7479 1933-7213 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0d7ac2b09ab8af1f7e617c765bdafad0Test http://europepmc.org/articles/PMC8423982Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0d7ac2b09ab8af1f7e617c765bdafad0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 18787479 19337213 |
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