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

NCT02323529 | Completed Phase 3

• 1 other identifier: Sobi.NTBC-003
• Study Type: interventional
• Target: 18
• Locations: 5 countries
• Sites: 6

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.

Conditions

Hereditary Tyrosinemia, Type I

Keywords

Orfadin; Nitisinone; NTBC

Outcome Measures

Primary Outcomes (1)

• Minimum serum concentration (Cmin) of nitisinone

  Sample collected immediately before administration of morning dose

  4 weeks

Secondary Outcomes (11)

• Maximum serum concentration (Cmax) of nitisinone

  4 weeks

• Cmax/Cmin ratio of nitisinone

  4 weeks

• Number of patients with Serum succinylacetone (s-SA) above lower limit of quantification (LLOQ)

  4 weeks

• Minimum serum concentration (Cmin) of nitisinone at possible occurence of s-SA above lower limit of quantification (LLOQ)

  4 weeks

• Number of patients with at least one adverse event

  4 weeks

Study Arms (1)

Nitisinone treatment group

EXPERIMENTAL

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

Interventions

Nitisinone DRUG

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

Nitisinone treatment group

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Patients who have been previously treated with once daily Orfadin, even if later converted to twice daily dosing.
• Pregnant women.
• Lactating women.
• Previous liver transplantation.
• Known hepatitis B, hepatitis C or HIV infection.
• Foreseeable inability to cooperate with given instructions or study procedures.

Sponsors & Collaborators

• Swedish Orphan Biovitrum: lead

Study Sites (6)

Swedish Orphan Biovitrum Investigational Site

Brussels, Belgium

Location

Swedish Orphan Biovitrum Investigational Site

Copenhagen, Denmark

Location

Swedish Orphan Biovitrum Investigational Site

Lyon, France

Location

Swedish Orphan Biovitrum Investigational Site

Giessen, Germany

Location

Swedish Orphan Biovitrum Investigational Site

Reutlingen, Germany

Location

Swedish Orphan Biovitrum Investigational site

Gothenburg, Sweden

Location

MeSH Terms

Conditions

Tyrosinemias

Interventions

nitisinone

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Anders Bröijersén, MD

  Swedish Orphan Biovitrum

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2014
• First Posted: December 23, 2014
• Study Start: December 1, 2014
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: November 11, 2015

Record last verified: 2015-11

Locations

FR (1); BE (1); DK (1); DE (2); SE (1)