Document Detail


Proarrhythmic safety of repeat doses of mirabegron in healthy subjects: a randomized, double-blind, placebo-, and active-controlled thorough QT study.
MedLine Citation:
PMID:  23149929     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Clinical Trial, Phase I; Journal Article; Randomized Controlled Trial     Date:  2012-11-14
Journal Detail:
Title:  Clinical pharmacology and therapeutics     Volume:  92     ISSN:  1532-6535     ISO Abbreviation:  Clin. Pharmacol. Ther.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-19     Completed Date:  2013-01-16     Revised Date:  2013-05-22    
Medline Journal Info:
Nlm Unique ID:  0372741     Medline TA:  Clin Pharmacol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  696-706     Citation Subset:  AIM; IM    
Affiliation:
St Paul's Cardiac Electrophysiology, London, UK.
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT01199523
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MeSH Terms
Descriptor/Qualifier:
Acetanilides / administration & dosage,  adverse effects*,  therapeutic use
Adolescent
Adrenergic beta-Agonists / administration & dosage,  adverse effects*,  therapeutic use
Adult
Anti-Infective Agents / adverse effects,  pharmacokinetics
Aza Compounds / adverse effects,  pharmacokinetics
Cross-Over Studies
Dose-Response Relationship, Drug
Double-Blind Method
Electrocardiography / drug effects*
Female
Heart Rate / drug effects
Humans
Long QT Syndrome / chemically induced*,  epidemiology
Male
Middle Aged
Quinolines / adverse effects,  pharmacokinetics
Sex Characteristics
Thiazoles / administration & dosage,  adverse effects*,  therapeutic use
Urinary Bladder, Overactive / drug therapy
Young Adult
Chemical
Reg. No./Substance:
0/Acetanilides; 0/Adrenergic beta-Agonists; 0/Anti-Infective Agents; 0/Aza Compounds; 0/Quinolines; 0/Thiazoles; MVR3JL3B2V/mirabegron; U188XYD42P/moxifloxacin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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