Evaluation of opicapone on cardiac repolarization in a thorough QT/QTc study
Identifieur interne : 000397 ( Main/Exploration ); précédent : 000396; suivant : 000398Evaluation of opicapone on cardiac repolarization in a thorough QT/QTc study
Auteurs : Roberto Pinto [France] ; Philippe L'Hostis [France] ; Alain Patat [France] ; Marie-Claude Homery [France] ; Amílcar Falcão [France] ; Teresa Nunes [France] ; José-Francisco Rocha [France] ; Patrício Soares-Da-Silva [France]Source :
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Abstract
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 tmax 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 tmax 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
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DOI: 10.1002/cpdd.188
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key="FR"></country></address></desc></hal:affiliation><country>France</country></affiliation></author><author><name sortKey="Soares Da Silva, Patricio" sort="Soares Da Silva, Patricio" uniqKey="Soares Da Silva P" first="Patrício" last="Soares-Da-Silva">Patrício Soares-Da-Silva</name><affiliation wicri:level="1"><hal:affiliation type="institution" xml:id="struct-333495" status="INCOMING"><orgName>Faculty of Medicine University of Porto</orgName><desc><address><country key="FR"></country></address></desc></hal:affiliation><country>France</country></affiliation></author></analytic><idno type="DOI">10.1002/cpdd.188</idno></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="mix" xml:lang="en"><term> COMT inhibitors</term><term> QT</term><term> QTc</term><term> opicapone</term><term>cardiac repolarization</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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 tmax 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 tmax 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</div></front></TEI><affiliations><list><country><li>France</li></country></list><tree><country name="France"><noRegion><name sortKey="Pinto, Roberto" sort="Pinto, Roberto" uniqKey="Pinto R" first="Roberto" last="Pinto">Roberto Pinto</name></noRegion><name sortKey="Falcao, Amilcar" sort="Falcao, Amilcar" uniqKey="Falcao A" first="Amílcar" last="Falcão">Amílcar Falcão</name><name sortKey="Homery, Marie Claude" sort="Homery, Marie Claude" uniqKey="Homery M" first="Marie-Claude" last="Homery">Marie-Claude Homery</name><name sortKey="L Hostis, Philippe" sort="L Hostis, Philippe" uniqKey="L Hostis P" first="Philippe" last="L'Hostis">Philippe L'Hostis</name><name sortKey="Nunes, Teresa" sort="Nunes, Teresa" uniqKey="Nunes T" first="Teresa" last="Nunes">Teresa Nunes</name><name sortKey="Patat, Alain" sort="Patat, Alain" uniqKey="Patat A" first="Alain" last="Patat">Alain Patat</name><name sortKey="Rocha, Jose Francisco" sort="Rocha, Jose Francisco" uniqKey="Rocha J" first="José-Francisco" last="Rocha">José-Francisco Rocha</name><name sortKey="Soares Da Silva, Patricio" sort="Soares Da Silva, Patricio" uniqKey="Soares Da Silva P" first="Patrício" last="Soares-Da-Silva">Patrício Soares-Da-Silva</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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