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Thorough QT/QTc Study in Patients With Advanced Parkinson's Disease: Cardiac Safety of Rotigotine
Author(s) -
Malik M,
Andreas JO,
Hnatkova K,
Hoeckendorff J,
Cawello W,
Middle M,
Horstmann R,
Braun M
Publication year - 2008
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2008.143
Subject(s) - qt interval , rotigotine , medicine , moxifloxacin , placebo , anesthesia , cardiology , heart rate , confidence interval , parkinson's disease , disease , antibiotics , microbiology and biotechnology , biology , blood pressure , alternative medicine , pathology
The potential effects of the dopamine agonist rotigotine on cardiac repolarization were studied in patients with Parkinson's disease, which affects electrocardiogram (ECG) quality. The parallel‐group trial was double‐blind and placebo‐ and positive (moxifloxacin 400 mg)‐controlled. After two 24‐h baseline ECGs, patients were randomized to rotigotine ( n = 66) or placebo ( n = 64). Twenty four–hour ECGs were recorded on days 14/15, 21/22, 28/29, 35/36, and 42/43 of a regimen involving weekly dose escalations of 4 mg/24 h (4 mg/24 h–24 mg/24 h). In 10‐s ECGs ( n = 357,948) selected from 24‐h records, QT measurements were manually verified and individually rate‐corrected (QTc). Assay sensitivity showed maximum mean 13.5 ms QTc prolongation after moxifloxacin with 95% confidence interval (CI) 11.8–15.2 ms. Rotigotine vs. placebo differences in time‐matched changes from baseline (54 data points/24 h) showed mean effects close to zero with upper one‐sided 95% CI <5 ms. Accurate, thorough QTc studies are possible even in patients with diseases that profoundly affect ECG quality. Rotigotine in supra‐ and therapeutic doses was shown not to affect cardiac repolarization. Clinical Pharmacology & Therapeutics (2008); 84 , 5, 595–603 doi: 10.1038/clpt.2008.143