http://orcid.org/0000-0003-3127-7486
![Sample our Bioscience journals, sign in here to start your access, Latest two full volumes FREE to you for 14 days]({"type":"image" , "src" : "/sda/5925/TOC-Subject-Sample-2021-Bioscience.jpg"})
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.
Trial registration: EudraCT identifier: 2014-001586-27
Trial registration: ClinicalTrials.gov identifier: NCT02191826.
Disclosure statement
This study was sponsored by SOM Innovation Biotech, S.L., Barcelona, Spain, but the sponsor was not involved in interpretation of the data or drafting of the manuscript.