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Dose Response Study of Nitisinone in Alkaptonuria (SONIA1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01828463
Recruitment Status : Completed
First Posted : April 10, 2013
Last Update Posted : June 11, 2014
Liverpool University Hospitals NHS Foundation Trust
Information provided by (Responsible Party):
Professor Lakshminarayan Ranganath, University of Liverpool

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.

Condition or disease Intervention/treatment Phase
Alkaptonuria Drug: Nitisinone Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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.
Study Start Date : May 2013
Actual Primary Completion Date : October 2013
Actual Study Completion Date : December 2013

Arm Intervention/treatment
No Intervention: no treatment
Experimental: Nitisinone 1mg
Drug: Nitisinone
doses 1, 2, 4 & 8 mg plus no treatment arm

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

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

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

Primary Outcome Measures :
  1. dose of nitisinone that decreases urinary homogentisic acid to near normal [ Time Frame: 4 weeks ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01828463

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United Kingdom
Royal Liverpool Hospital
Liverpool, Merseyside, United Kingdom, L7 8XP
Sponsors and Collaborators
University of Liverpool
Liverpool University Hospitals NHS Foundation Trust
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Principal Investigator: L Ranganath Royal Liverpool & Broadgreen University Hospitals NHS Truts
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Professor Lakshminarayan Ranganath, Consultant in Metabolic medicine, University of Liverpool Identifier: NCT01828463    
Other Study ID Numbers: UoL000928
First Posted: April 10, 2013    Key Record Dates
Last Update Posted: June 11, 2014
Last Verified: June 2014
Additional relevant MeSH terms:
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Amino Acid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Pathologic Processes
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action