Dose Response Study of Nitisinone in Alkaptonuria

Alkaptonuria Clinical Trial

— SONIA1  

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01828463
• Other study ID #: UoL000928
• Status: Completed
• Phase: Phase 2
• First received: April 5, 2013
• Last updated: June 10, 2014
• Start date: May 2013
• Est. completion date: December 2013

Study information

• Verified date: June 2014
• Source: University of Liverpool
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: December 2013
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alkaptonuria

Intervention

Drug:
• Nitisinone
doses 1, 2, 4 & 8 mg plus no treatment arm

Locations

Country	Name	City	State
United Kingdom	Royal Liverpool Hospital	Liverpool	Merseyside

Sponsors (2)

Lead Sponsor	Collaborator
University of Liverpool	Royal Liverpool and Broadgreen University Hospitals NHS Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	dose of nitisinone that decreases urinary homogentisic acid to near normal		4 weeks	No