Efficacy and Safety of Once Daily Dosing Compared to Twice Daily Dosing of Nitisinone in HT-1

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Disease Information

Descriptive Information
Brief Title † Efficacy and Safety of Once Daily Dosing Compared to Twice Daily Dosing of Nitisinone in HT-1
Official Title † Open-label, Multicentre, Multiple-dose Trial to Evaluate Pharmacokinetics, Efficacy and Safety of Once Daily Dosing Compared to Twice Daily Dosing of Orfadin in Patients Diagnosed With Hereditary Tyrosinemia Type 1
Brief Summary 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.
Detailed Description 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 (
Study Phase Phase 3
Study Type † Interventional
Study Design † Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary Outcome Measure † Minimum serum concentration (Cmin) of nitisinone
Secondary Outcome Measure † Maximum serum concentration (Cmax) of nitisinone
Condition † Hereditary Tyrosinemia, Type I
Intervention † DrugNitisinone
Study Arms / Comparison Groups Nitisinone treatment group 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.
Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information
Recruitment Status † Drug
Estimated Enrollment † 20
Start Date † December 2014
Completion Date December 2015
Primary Completion Date November 2015
Eligibility Criteria † Inclusion Criteria: - Male and female patients of all ages diagnosed with HT-1. - Patients currently well-controlled, as judged by the investigator, on twice daily (or more frequent) dosing with Orfadin. - Stable lab values, including liver values
Gender Both
Ages N/A - N/A
Accepts Healthy Volunteers No
Contacts †† Ulrika Stein Grive, B.Sc, 0046 8 697 20 00,
Location Countries † Belgium
Administrative Information
NCT ID † NCT02323529
Organization ID Sobi.NTBC-003
Secondary IDs ††
Responsible Party Sponsor
Study Sponsor † Swedish Orphan Biovitrum
Collaborators ††
Investigators † Study Director: Anders Bröijersén, MD, Swedish Orphan Biovitrum
Information Provided By
Verification Date August 2015
First Received Date † December 18, 2014
Last Updated Date August 11, 2015
† Required WHO trial registration data element.
†† WHO trial registration data element that is required only if it exists.
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