Dose Response Study of Nitisinone in Alkaptonuria

Exclusion Criteria

• •The presence of any of the following will exclude a subject from inclusion in the study:
• •1. Non-alkaptonuria causes of ochronosis.
• •2. Currently pregnant or lactating.
• •3. Known allergy to nitisinone or any of the constituents of the investigational product.
• •4. Use of a protein-restricted diet
• •5. Dietary habits or use of homeopathic therapies that interfere with tyrosine catabolism.
• •6. Current keratopathy, contact lens use or uncontrolled glaucoma.
• •7. Current malignancy.
• •8. Uncontrolled hypertension (blood pressure greater than 180 systolic or greater than 95 diastolic).
• •9. Electrocardiogram changes indicative of myocardial infarction, arrhythmia, tachycardia, bradycardia, left bundle branch block.
• •10. Chest radiographic abnormalities, including an infiltrative, mass, congestive heart failure, embolism, atelectasis.
• •11. Serum potassium \< 3.0 mmol/L.
• •12. eGFR \< 60 mL/min.
• •13. Any hepatic enzymes greater than 3 x upper limit of normal.
• •14. Haemoglobin \< 10.0 g/dL.
• •15. Platelets less than 100 x 109/L.
• •16. WBC less than 3.0 x 109/L.
• •17. ESR greater than 100 mm/h.
• •18. History of alcohol or drug abuse.
• •19. Participation in another clinical trial within 3 months of randomisation.
• •20. Treatment with nitisinone within 3 months of randomisation
• •21. Psychiatric illness or neurological disease that interferes with compliance or communication with health care personnel.
• •22. Any other medical condition which in the opinion of the investigator makes the subject unsuitable for inclusion.
• •23. Foreseeable inability to cooperate with given instructions or study procedures.