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

• Register: ClinicalTrials.gov
• Last refreshed on: 23 November 2015
• Main ID: NCT02323529
• Date of registration: 18/12/2014
• Prospective Registration: No
• Primary sponsor: Swedish Orphan Biovitrum
• Public title: Efficacy and Safety of Once Daily Dosing Compared to Twice Daily Dosing of Nitisinone in HT-1 HT-1
• Scientific 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
• Date of first enrolment: December 2014
• Target sample size: 18
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02323529
• Study type: Interventional
• Study design: Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 3

Countries of recruitment

Belgium, Denmark, France, Germany, Sweden

Contacts

• Name: Anders Bröijersén, MD
• Affiliation: Swedish Orphan Biovitrum

Key inclusion & exclusion 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 <2 ULN (ALP, ALT, AST, bilirubin, INR).

- Women of childbearing potential willing to use adequate contraception

- Signed informed consent/assent.

Exclusion Criteria:

- Patients who have been previously treated with once daily Orfadin, even if later
converted to twice daily dosing.

- Any medical condition which in the opinion of the investigator makes the patient
unsuitable for inclusion.

- Enrollment in another concurrent clinical interventional study within three months
prior to inclusion in this study.

- Pregnant women.

- Lactating women.

- Previous liver transplantation.

- Patients who have recently (past 4 weeks prior to inclusion) started any new
medication for a previously undiagnosed illness/disease.

- Known hepatitis B, hepatitis C or HIV infection.

- Foreseeable inability to cooperate with given instructions or study procedures.



Age minimum: N/A
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Hereditary Tyrosinemia, Type I

Intervention(s)

Drug: Nitisinone

Primary Outcome(s)

Minimum serum concentration (Cmin) of nitisinone [Time Frame: 4 weeks]

Secondary Outcome(s)

Cmax/Cmin ratio of nitisinone [Time Frame: 4 weeks]

Number of patients with at least one serious adverse events [Time Frame: 4 weeks]

Number of patients with at least one adverse event leading to study discontinuation [Time Frame: 4 weeks]

Number of patients with at least one study drug related adverse events [Time Frame: 4 weeks]

Number of patients with Serum succinylacetone (s-SA) above lower limit of quantification (LLOQ) [Time Frame: 4 weeks]

Serum-alpha fetoprotein (µg/L) [Time Frame: 4 weeks]

Number of patients with at least one adverse event [Time Frame: 4 weeks]

Minimum serum concentration (Cmin) of nitisinone at possible occurence of s-SA above lower limit of quantification (LLOQ) [Time Frame: 4 weeks]

Maximum serum concentration (Cmax) of nitisinone [Time Frame: 4 weeks]

Number of patients with at least one non-serious adverse event [Time Frame: 4 weeks]

Serum-tyrosine (µmol/L) [Time Frame: 4 weeks]

Secondary ID(s)

Sobi.NTBC-003

Source(s) of Monetary Support

Please refer to primary and secondary sponsors