Nitisinone (NTBC) In Different Age Groups Of Patients With Alkaptonuria

• Status: Completed
• Trial end date: 2016-07-01
• Target enrollment: 0
• Participant gender: All

Summary

Nitisinone is a potent inhibitor of the enzyme that catalyzes the formation of homogentisic acid, and should be an even more logical treatment for alkaptonuria than for tyrosinemia, for which it has been approved by the FDA.The objective of this research is to explore reported age related differences in toxicity of nitisinone and its pharmacokinetic underpinnings and to develop an optimal therapeutic requirement for a targeted population of presymptomatic patients. The additional effect of mixtures of amino acids excluding tyrosine will be explored to take advantage of protein synthesis to avoid elevations of tyrosine that would otherwise limit the optimal dosage of nitisinone. The study is designed to treat patients and find the optimal dosage of nitisinone to obtain maximal reduction in levels of homogentisic acid and maintain safe levels of tyrosine.

The long term objective in the target population of pre-symptomatic patients is the prevention of the characteristic effects on joint cartilage and tendons.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of California, San Diego
• Treatments: Nitisinone

Criteria

Inclusion Criteria:

1. Diagnosis of alkaptonuria with documented increased excretion of homogentisic acid

2. Willing and able to provide written, signed informed consent, or age appropriate written assent and written informed consent by a legally authorized representative after the study has been explained, prior to any research-related procedures.

3. Willing and able to be seen in the UCSD Clinical Center for Research or a satellite site for the study visits

4. Possession of insurance coverage for standard of care procedures, clearly stated in the consent forms

Exclusion Criteria:

1. Baseline tyrosine level above 250 mmol/mL

2. Baseline serum creatinine, creatine kinase, or transaminases 2x upper limit of normal

3. Baseline anemia or thrombocytopenia

4. Current participation in another investigational medication trial.

5. Pregnant or lactating women

6. Current keratopathy, contact use or uncontrolled glaucoma

7. History myocardial infarction or arrhythmia

8. History of pulmonary insufficiency

9. Psychiatric illness that may interfere with compliance or communication

10. Current malignancy or hypertension