Alkaptonuria (AKU) - a serious, autosomal recessive, multisystem disorder
Conditions
Interventions
Product Name: Orfadin 4mg/ml
Pharmaceutical Form: Oral suspension
Sponsors
University of Liverpool (UniLiv)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Diagnosis of AKU verified by previously documented elevated urinary homogentisic acid excretion. 2. Age =18 years. 3. Willing and able to visit the investigational site for study visits. 4. Signed written informed consent given. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 37 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 3
Exclusion criteria
Exclusion criteria: 1. Currently pregnant or lactating. 2. Female patient of child-bearing potential not using a reliable method of contraception. 3. Known allergy to nitisinone or any of the constituents of the investigational product. 4. Current keratopathy or uncontrolled glaucoma. 5. Current malignancy. 6. Uncontrolled hypertension (blood pressure greater than 180 mmHg systolic or greater than 95 mmHg diastolic). 7. Unstable cardiovascular disease. 8. Serum potassium 3 x upper limit of normal. 11. Hemoglobin < 10.0 g/dL. 12. Platelets < 100 x 109/L. 13. White blood count < 3.0 x 109/L. 14. History of alcohol or drug abuse. 15. Participation in another clinical study within 3 months of randomization. 16. Treatment with nitisinone within 60 days of randomization. 17. Psychiatric illness or neurological disease that interferes with compliance or communication with health care personnel. 18. Any other medical condition which in the opinion of the investigator makes the patient unsuitable for inclusion. 19. Foreseeable inability to cooperate with given instructions or study procedures.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: • To investigate the effect of different doses of once daily nitisinone on plasma homogentisic acid concentration (p-HGA) and plasma tyrosine concentration (p-Tyr) in patients with alkaptonuria. • To determine the pharmacokinetics (PK) of nitisinone at steady state and to test for PK dose-proportionality. • To describe the relationship between PK variables of nitisinone, u-HGA24, p-HGA and p-Tyr. • To assess the safety of nitisinone at doses relevant for the treatment of alkaptonuria. ;Main Objective: To investigate the effect of different doses of once daily nitisinone on 24-hour urinary homogentisic acid excretion (u-HGA24) in patients with alkaptonuria after 4-weeks treatment.;Primary end point(s): u-HGA24 after 4 weeks of treatment with nitisinone.;Timepoint(s) of evaluation of this end point: A follow-up phone call will take place 2 weeks (+/- 3 days) after the Final Visit. The patient will be questioned about concomitant medication and adverse events. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • u-HGA24 after 1, 2 and 3 weeks of treatment with nitisinone. • Proportion of patients achieving normal levels of u-HGA24 at weeks 1, 2, 3 and 4. • p-HGA and p-Tyr at Weeks 1, 2, 3, and 4. • 24-hour plasma HGA and plasma tyrosine profiles at baseline and Week 4. • Nitisinone steady-state pharmacokinetic variables. • Adverse events, clinical chemistry and haematology, vital signs, ECG. ; Timepoint(s) of evaluation of this end point: Visit 2: The 24-hour urine collection will be done at home. Patients should begin collection in the morning, immediately after taking the daily dose of study medication. Collection ends the following morning at the same time. Visit 3: As for Visit 1. The patient will take the last dose of study medication immediately before the 24-hour collection period begins. | — |
Countries
United Kingdom
Contacts
Public ContactPrincipal Investigator
Royal Liverpool Unversity Hospital (RLUH)
Outcome results
None listed