Patients with familial amyloid polyneuropathy (FAP), asymptomatic carriers and healthy volunteers MedDRA version: 17.0 Level: LLT Classification code 10057949 Term: Familial amyloid polyneuropathy System Organ Class: 100000004850
Conditions
Interventions
Trade Name: Tasmar
Pharmaceutical Form: Coated tablet
INN or Proposed INN: TOLCAPONE
CAS Number: 134308-13-7
Current Sponsor code: SOM0226
Concentration unit: mg milligram(s)
Concentration type: equal
Sponsors
SOM Innovation Biotech SL (SOM Biotech)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Participant is willing and able to give informed consent for participation in the study. - Male or Female, aged 18 years or above at time of consent. - Two cohorts defined by TTR variant: Wild type TTR: healthy patients V30M TTR mutant: Asymptomatic carriers with documented mutation V30M TTR or diagnosed TTR-FAP patients (stage 1 or 2) not undergoing pharmacological treatment with Vyndaqel®. - Body Mass Index (BMI) > 17.5 kg/m2 - Female participants of child bearing potential and male participants whose partner is of child bearing potential must be willing to ensure that they or their partner use effective contraception during the study and for 2 month thereafter. - Able (in the Investigators opinion) and willing to comply with all study requirements. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: The participant may not enter the study if ANY of the following apply: - Female participants who is pregnant, lactating or planning pregnancy during the course of the study. - Evidence of history of clinically significant hepatic disease. - An ALT or AST measurement > 2 times the ULN (Upper Limit of Normal). - Scheduled elective surgery or other procedures requiring general anaesthesia during the study. - Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant?s ability to participate in the study. - Donation of blood during the study or within the past 4 weeks. - Treatment (during the study or within the past 4 weeks) with a prescription or investigational drug for the treatment of TTR amyloidosis. - Treatment with NSAIDs during the study or within the past 4 weeks. The following NSAID are allowed: acetylsalicylic acid, etodolac, ibuprofen, indomethacin, ketoprofen, nabumetone, naproxen, nimesulide, piroxicam and sulindac
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Determine whether SOM0226 induces TTR stabilization by evaluating whether treatment with SOM0226 prevents urea-induced denaturation of tetrameric TTR.;Secondary Objective: - The secondary objective is to determine the plasma concentration of SOM0226 needed to induce a maximal stabilization of TTR in healthy volunteers, patients and asymptomatic carriers. - A pharmacodynamics assessment will be used to determine an effective dose of SOM0226 to confer TTR stabilization, by determining the molar ratio SOM0226:TTR that must be reached in plasma to induce maximal stabilization of TTR in healthy individuals, patients and asymptomatic carriers.;Primary end point(s): TTR stabilization will be measured by determining the concentration of tetrameric TTR after denaturation. The ratio of TTR tetramer after denaturation / TTR tetramer before denaturation of plasma samples from treated subjects will be compared to their baseline ratio. TTR stabilization will be determined as percentage of the baseline ratio. TTR stabilization will be measured in plasma samples obtained from each participant before first dose and at different times during each treatment period. In terms of assessing efficacy, a positive result will be a TTR stabilization value superior to 20%.;Timepoint(s) of evaluation of this end point: Phase A (24 hours) and Phase B (32 hours). Between these two phases there is a washout period of 6 weeks (+-2 weeks) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - The pharmacodynamics characteristics of SOM0226 will be assessed to determine which plasma SOM0226:TTR molar ratio is needed to reach a plateau of TTR stabilization. - The concentration of SOM0226 will be determined in all plasma samples obtained at different times during each treatment period. - The concentration of TTR will be determined in all plasma samples, and the molar ratio SOM0226:TTR in each sample will be calculated. - Safety will be assessed by ALT and AST liver function measures in samples obtained at the end of each treatment phase (24 hours in Phase A and 32 hours in Phase B).;Timepoint(s) of evaluation of this end point: Phase A (24 hours) and Phase B (32 hours). Between these two phases there is a washout period of 6 weeks (+-2 weeks) | — |
Countries
Spain
Contacts
Public ContactMiriam García Diez
ARO-VHIR
Outcome results
None listed