Transthyretin stabilization activity of the catechol-O-methyltransferase inhibitor tolcapone (SOM0226) in hereditary ATTR amyloidosis patients and asymptomatic carriers: proof-of-concept study.
Amyloid
; 26(2): 74-84, 2019 Jun.
Article
en En
| MEDLINE
| ID: mdl-31119947
ABSTRACT
Objective:
To assess the transthyretin (TTR) stabilization activity of tolcapone (SOM0226) in patients with hereditary ATTR amyloidosis, asymptomatic carriers and healthy volunteers.Methods:
A phase IIa proof-of-concept trial included two phases separated by a 6-week washout period. Phase A single 200 mg dose of tolcapone; phase B three 100 mg doses taken at 4 h intervals. The primary efficacy variable was TTR stabilization.Results:
Seventeen subjects were included (wild type, n = 6; mutation TTR Val30Met, n = 11). TTR stabilization was observed in all participants. Two hours after dosing, 82% of participants in phase A and 93% of those in phase B reached a TTR stabilization value of at least 20%. In phase A, there was an increase of 52% in TTR stabilization vs baseline values 2 h after dosing, which decreased to 22.9% at 8 h. In phase B, there was a significant increase of 38.8% in TTR stabilization 2 h after the first 100 mg dose. This difference was maintained after 10 h and decreased after 24 h. No serious adverse events were observed.Conclusions:
The ability of tolcapone for stabilizing TTR supports further development and repositioning of the drug for the treatment of ATTR amyloidosis. EudraCT trial number 2014-001586-27 ClinicalTrials.gov Identifier NCT02191826.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Prealbúmina
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Neuropatías Amiloides Familiares
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Agregación Patológica de Proteínas
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Prueba de Estudio Conceptual
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Tolcapona
Tipo de estudio:
Prognostic_studies
Límite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Amyloid
Asunto de la revista:
BIOQUIMICA
Año:
2019
Tipo del documento:
Article
País de afiliación:
España