Dose Response Study of Nitisinone in Alkaptonuria

Inclusion criteria

A subject must fulfil the following criteria in order to be included in the study:

• Diagnosis of alkaptonuria verified by documented elevated urinary homogentisic acid excretion.
• Age ≥18 years.
• Willing and able to visit the investigational site for study visits.
• Signed written informed consent obtained.

Exclusion criteria

The presence of any of the following will exclude a subject from inclusion in the study:

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