| Proarrhythmic Safety of Repeat Doses of Mirabegron in Healthy Subjects: A Randomized, Double-Blind, Placebo-, and Active-Controlled Thorough QT Study. | |
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MedLine Citation:
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PMID: 23149929 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Potential effects of the selective β(3)-adrenoceptor agonist mirabegron on cardiac repolarization were studied in healthy subjects. The four-arm, parallel, two-way crossover study was double-blind and placebo- and active (moxifloxacin)-controlled. After 2 baseline ECG days, subjects were randomized to one of eight treatment sequences (22 females and 22 males per sequence) of placebo crossed over with once-daily (10 days) 50, 100, or 200 mg mirabegron or a single 400-mg moxifloxacin dose on day 10. In each period, continuous ECGs were recorded at two baselines and on the last drug administration day. The lower one-sided 95% confidence interval for moxifloxacin effect on QTcI was >5 ms, demonstrating assay sensitivity. According to ICH E14 criteria, mirabegron did not cause QTcI prolongation at the 50-mg therapeutic and 100-mg supratherapeutic doses in either sex. Mirabegron prolonged QTcI interval at the 200-mg supratherapeutic dose (upper one-sided 95% CI >10 ms) in females, but not in males.Clinical Pharmacology & Therapeutics (2012); advance online publication 14 November 2012. doi:10.1038/clpt.2012.181. |
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Authors:
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M Malik; E M van Gelderen; J H Lee; D L Kowalski; M Yen; R Goldwater; S K Mujais; M P Schaddelee; P de Koning; A Kaibara; S S Moy; J J Keirns |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-11-14 |
Journal Detail:
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Title: Clinical pharmacology and therapeutics Volume: - ISSN: 1532-6535 ISO Abbreviation: Clin. Pharmacol. Ther. Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-11-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372741 Medline TA: Clin Pharmacol Ther Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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St Paul's Cardiac Electrophysiology, London, UK. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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