Dose Response Study of Nitisinone in Alkaptonuria

Inclusion criteria A subject must fulfil the following criteria in order to be included in the study: 1. Diagnosis of alkaptonuria verified by 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 obtained. 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.