A Phase 3 interventional study of Nitisinone in Hereditary Tyrosinemia, Type I, sponsored by Swedish Orphan Biovitrum. Completed at 6 sites in 5 countries. Per ClinicalTrials.gov, last updated 2015-11-11.
Sponsored by Swedish Orphan Biovitrum · Phase 3, Interventional, and Treatment
The purpose of this study is to look at the steady-state serum concentrations of nitisinone when switching from twice daily and once daily dosing.
Nitisinone (Orfadin) is used in the treatment of hereditary tyrosinemia type 1(HT-1), an inborn error of metabolism. The clinical study that forms the basis for licensing of nitisinone in the treatment of HT-1 used twice daily dosing. This became the recommended dosing frequency of nitisinone stated in the Summary of Product Characteristics. Later on, when the half-life became know (around 50 hours in adults), many physicians started to use once daily dosing. The suitability of once daily dosing and especially of switching patients from twice to once daily dosing has not been documented. The aim with this study is therefore to investigate the effect on nitisinone serum concentrations (Cmax and Cmin) and possible clinical consequences of a lower dosing frequency.
This one-way crossover study consists of three periods; Screening period, Treatment period 1 and Treatment period 2. The study starts with a screening period (Visit 1-1b) that may be up to 6 weeks long. This is followed by two treatment periods of at least 4 weeks each. During Treatment period 1 (Visits 2-3), the patient will take Orfadin twice daily. During Treatment period 2 (Visits 4-5), the patient will take Orfadin once daily. The dose of nitisinone in the study will be the same as the one prescribed at completed screening visit. Dose will be 1-2 mg/kg body weight. The total treatment period will be at least 8 weeks.
At least 20 patients with a minimum of 3 patients in each of the following age groups will be included; infants (\< 2 years), children (2-\<12 years), adolescents (12-\<18 years) and adults (≥18 years).
Determination of succinylacetone (SA) in blood (serum/plasma) and/or urine will be performed both locally and at a central Good Laboratory Practice certified laboratory (Dry Blood Spot sample). The purpose of the local sample is to provide the investigator with more or less immediate results to determine if a dose adjustment is needed before the patient enters either of the two treatment periods. Results from samples analyzed at the central laboratory, including determination of nitisinone, will be used in the evaluation of pharmacokinetics, efficacy and safety during the two treatment periods.
21 studies on the registry are indexed under Tyrosinemias; 3 are open to participants now.
This study's enrollment of 18 is close to the median of 20 across 12 interventional studies indexed under Tyrosinemias.
Browse Tyrosinemias studies →Swedish Orphan Biovitrum is the lead sponsor of 78 studies on the registry; 4 are open to participants now.
Of its 17 completed or terminated interventional studies of FDA-regulated products, 15 (88%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
All patients in the study will first be put on twice daily dosing of nitisinone for 4 weeks. This will then be followed by once daily dosing of nitisinone for 4 weeks.
Drug: Nitisinone
All patients in the study will first be put on twice daily dosing of nitisinone for 4 weeks. This will then be followed by once daily dosing of nitisinone for 4 weeks. The dose of nitisinone in the study will be the same as the one prescribed at completed screening visit. Dose will be 1-2 mg/kg body weight.
Also known as: Orfadin
Minimum serum concentration (Cmin) of nitisinone
Sample collected immediately before administration of morning dose
Time frame: 4 weeks
Maximum serum concentration (Cmax) of nitisinone
Sample collected 3-4 hours post dose
Time frame: 4 weeks
Cmax/Cmin ratio of nitisinone
Time frame: 4 weeks
Number of patients with Serum succinylacetone (s-SA) above lower limit of quantification (LLOQ)
Time frame: 4 weeks
Minimum serum concentration (Cmin) of nitisinone at possible occurence of s-SA above lower limit of quantification (LLOQ)
Cmin of nitisinone will be listed for patients with s-SA above LLOQ
Time frame: 4 weeks
Number of patients with at least one adverse event
Total and by system organ class and preferred term (MedDRA)
Time frame: 4 weeks
Number of patients with at least one serious adverse events
Total and by system organ class and preferred term (MedDRA)
Time frame: 4 weeks
Number of patients with at least one study drug related adverse events
Total and by system organ class and preferred term (MedDRA)
Time frame: 4 weeks
Number of patients with at least one non-serious adverse event
Total and by system organ class and preferred term (MedDRA)
Time frame: 4 weeks
Number of patients with at least one adverse event leading to study discontinuation
Total and by system organ class and preferred term (MedDRA)
Time frame: 4 weeks
Serum-tyrosine (µmol/L)
Descriptive statistics of s-tyrosine
Time frame: 4 weeks
Serum-alpha fetoprotein (µg/L)
Descriptive statistics of s-alpha fetoprotein
Time frame: 4 weeks
This study is completed, as verified in Nov 2015. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Swedish Orphan Biovitrum