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Evaluation of opicapone on cardiac repolarization in a thorough QT/QTc study
Author(s) -
Pinto Roberto,
l'Hostis Philippe,
Patat Alain,
Homery MarieClaude,
Falcão Amílcar,
Nunes Teresa,
Rocha JoséFrancisco,
SoaresdaSilva Patrício
Publication year - 2015
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.188
Subject(s) - medicine , moxifloxacin , placebo , qt interval , confidence interval , anesthesia , cardiology , crossover study , repolarization , antibiotics , electrophysiology , alternative medicine , pathology , microbiology and biotechnology , biology
Opicapone, a novel third‐generation catechol‐O‐methyltransferase inhibitor for use as adjunctive therapy in levodopa‐treated Parkinson's disease patients, was investigated on cardiac repolarization in healthy adult volunteers. This was a single‐center, randomized, double‐blind, placebo‐controlled, open‐label active‐controlled, 4‐period crossover study conducted in 64 subjects. In each period, subjects received a single oral dose of 50 mg opicapone, 800 mg opicapone, placebo, or 400 mg moxifloxacin and 24‐hour 12‐lead Holter monitoring was performed on day ‐1 (baseline) and after each single dose. After a single oral administrations of 50 and 800 mg opicapone, opicapone was the major entity in the circulation, with a median t max of 1.5–2.0 hours. Opicapone was rapidly eliminated, with an elimination half‐life of 1–2 hours. There was no clinically relevant effect of 50 and 800 mg opicapone versus placebo on cardiac depolarization or repolarization. All upper bounds of the 1‐sided 95% confidence interval (CI) were below 10 milliseconds, confirming that opicapone has no QT‐prolonging effect. Moxifloxacin caused an increase in the QTcI, with a lower bound of the 2‐sided 95% CI always higher than 5 milliseconds, around the t max of peak concentration, demonstrating assay sensitivity. In conclusion, administration of opicapone at therapeutic (50 mg) and supratherapeutic (800 mg) doses did not induce a clinically significant prolongation of the QTc interval.