hereditary tyrosinemia type 1 MedDRA version: 17.1 Level: LLT Classification code 10069462 Term: Tyrosinemia type I System Organ Class: 100000004850
Conditions
Interventions
Trade Name: Orfadin
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: NITISINONE
CAS Number: 104206-65-7
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 2-10
Sponsors
Swedish Orphan Biovitrum AB (Publ)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female patients of all ages diagnosed with HT-1. 2. Patients currently well-controlled, as judged by the investigator, on twice daily (or more frequent) dosing with Orfadin. 3. Stable lab values, including liver values =65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Patients who have been previously treated with once daily Orfadin, even if later converted to twice daily dosing. 2. Any medical condition which in the opinion of the investigator makes the patient unsuitable for inclusion. 3. Enrollment in another concurrent clinical interventional study within three months prior to inclusion in this study. 4. Pregnant women. 5. Lactating women. 6. Previous liver transplantation 7. Patients who have recently (past 4 weeks prior to inclusion) started any new medication for a previously undiagnosed illness/disease. 8. Known hepatitis B, hepatitis C or HIV infection. 9. Foreseeable inability to cooperate with given instructions or study procedures.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the steady-state exposure to nitisinone during once and twice daily dosing of Orfadin;Secondary Objective: - To evaluate the efficacy of Orfadin during once daily dosing. - To evaluate the safety of Orfadin during once and twice daily dosing.;Primary end point(s): Minimum (Cmin) serum concentrations of nitisinone after at least 4 weeks of treatment on each dosage regimen. Cmin = concentration in the sample taken immediately before dosing.;Timepoint(s) of evaluation of this end point: D1, after 4w + 10 days on 2x daily dosing with IMP - predose, after 4w + 10 days on 1x daily dosing with IMP - predose | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - maximum (Cmax) serum concentrations of nitisinone and the Cmax/Cmin ratio, after at least 4 weeks of treatment on each dosage regimen. Cmax = concentration in a sample taken any time from 3 to 4 hours after dosing. - Serum succinylacetone (s-SA) after at least 4 weeks of treatment. - Serum concentration of nitisinone, Cmin at possible occurrence of s-SA above lower limit of quantitation (LLOQ). -Safety and tolerability assessments; including Adverse Events (AEs), routine clinical chemistry tests including serum alpha fetoprotein (s-AFP), hepatic and renal function, coagulation and serum tyrosine.;Timepoint(s) of evaluation of this end point: - maximum (Cmax) serum concentrations of nitisinone and the Cmax/Cmin ratio: after 4w + 10 days on 2x daily dosing with IMP - 3-4 hrs postdose, 4w + 10 days on 1x daily dosing with IMP - 3-4 hrs postdose - sSA, serum concentration of nitisinone, Cmin at possible occurrence of s-SA above lower limit of quantitation (LLOQ) and laboratory safety: D1, after 4w+10 days on 2x daily dosing with IMP, after 4w + 10 days on 1x daily dosing with IMP AEs: D1 - last study visit | — |
Countries
Belgium, Denmark, Sweden
Contacts
Public ContactKarin Becker
Swedish Orphan Biovitrum AB (Publ)
Outcome results
None listed