Dose Response Study of Nitisinone in Alkaptonuria

An International, Multicentre, Randomised, Open-label, No-treatment Controlled, Parallel-group, Dose-response Study to Investigate the Effect of Once Daily Nitisinone on 24-hour Urinary Homogentisic Acid Excretion in Patients With Alkaptonuria After 4 Weeks Treatment.

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01828463

Acronym

SONIA1

Enrollment

Registered

2013-04-10

Start date

2013-05-31

Completion date

2013-12-31

Last updated

2014-06-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Alkaptonuria

Brief summary

SONIA 1 is an international, multicentre, randomised, open-label, no-treatment controlled, parallel group, dose-response study to investigate the effect of once daily nitisinone on 24-hour urinary homogentisic acid excretion in patients with alkaptonuria after 4-weeks treatment. They study will identify the optimal dose to decrease urine homogentisic acid to near normal levels.

Interventions

DRUGNitisinone

doses 1, 2, 4 & 8 mg plus no treatment arm

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame
dose of nitisinone that decreases urinary homogentisic acid to near normal	4 weeks

Countries

United Kingdom

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026