A non-interventional Post Authorization Safety Study (PASS) to evaluate long-term safety of Orfadin treatment in hypertyrosinemia type 1 (HT-1) patients in standard clinical care (OPAL)

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness
• Data collection methods:
  Combined primary data collection and secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

  Other
• Non-interventional study design, other:
  Non-comparative, multicenter Post Authorization Safety Study (PASS)

Study drug and medical condition

• Name of medicine:
  ORFADIN
• Anatomical Therapeutic Chemical (ATC) code:
  (A16AX04) nitisinone

  nitisinone
• Medical condition to be studied:
  Tyrosinaemia
• Additional medical condition(s):
  Hereditary Tyrosinemia type 1 (HT-1)

Population studied

• Short description of the study population:
  All HT-1 patients on Orfadin treatment in standard clinical care at study entry as well as patients diagnosed and starting Orfadin treatment during the time of the study
• Age groups:
  • Paediatric Population (< 18 years)

    • Neonate

      • Preterm newborn infants (0 – 27 days)
      • Term newborn infants (0 – 27 days)
    • Infants and toddlers (28 days – 23 months)
    • Children (2 to < 12 years)
    • Adolescents (12 to < 18 years)
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)

      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)
• Special population of interest:
  Other
• Special population of interest, other:
  Hypertyrosinemia type 1 (HT-1) patients
• Estimated number of subjects:
  300

Study design details

• Main study objective:
  The primary objective is to assess long-term safety of Orfadin used in standard clinical practice to treat patients with HT-1.
• Outcomes:
  The primary endpoints are occurrence of Adverse Events (AE) related to hepatic, renal, ophthalmic, hematological or cognitive, developmental function. Occurrence of other AEsDiscontinuation of Orfadin treatmentOccurrence of liver transplantation or deathExtent of exposureLab: tyrosine, phenylalanin, succinylacetone, alfa-fetoproteinTreatment and diet complianceOverall clinical condition
• Data analysis plan:
  Demographics and other patient characteristics will be presented descriptively. The proportion of patients who experience events defined in the primary endpoints and the associated two-sided 95% confidence intervals will be calculated as well as incidence rate expressed as frequency of events per cumulative exposure expressed in patient years. The AEs will be coded using the MedDRA (Medical Dictionary for Regulatory Activities) and tabulated by seriousness, system organ class and preferred term. Both the total number of events and the number of patients reporting each event at least once will be tabulated as well as incidence rate per patient years on Orfadin treatment. Laboratory data will be presented graphically and summarized using descriptive statistics. Exposure will be summarized descriptively.