A Pooled Analysis of Three Randomized Phase I/IIa Clinical Trials Confirms Absence of a Clinically Relevant Effect on the QTc Interval by Umibecestat.
Clin Transl Sci
; 13(6): 1316-1326, 2020 11.
Article
em En
| MEDLINE
| ID: mdl-32583957
ABSTRACT
Umibecestat, an orally active ß-secretase inhibitor, reduces the production of amyloid beta-peptide that accumulates in the brain of patients with Alzheimer's disease. The echocardiogram effects of umibecestat, on QTcF (Fridericia-corrected QT), on PR and QRS and heart rate (HR), were estimated by concentration-effect modeling. Three phase I/II studies with durations up to 3 months, with 372 healthy subjects over a wide age range, including both sexes and 2 ethnicities, were pooled, providing a large data set with good statistical power. No clinically relevant effect on QTcF, PR interval, QRS duration, or HR were observed up to supratherapeutic doses. The upper bound of 90% confidence intervals of the ∆QTcF was below the 10 ms threshold of regulatory concern for all concentrations measured. Prespecified sensitivity analysis confirmed the results in both sexes, in those over and below 60 years, and in Japanese subjects. All conclusions were endorsed by the US Food and Drug Administration (FDA).
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Oxazinas
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Síndrome do QT Longo
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Ácido Aspártico Endopeptidases
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Eletrocardiografia
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Secretases da Proteína Precursora do Amiloide
Tipo de estudo:
Clinical_trials
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Prognostic_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Clin Transl Sci
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Suíça