AlkaptonuriaPhase 2SONIA1NCT01828463
Dose Response Study of Nitisinone in Alkaptonuria
A Phase 2 study testing Nitisinone in people with Alkaptonuria, run by University of Liverpool at 1 site in United Kingdom.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Alkaptonuria
- What is being tested?
- Nitisinone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- May 2013to Dec 2013
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Royal Liverpool Hospital
Liverpool, Merseyside, L7 8XP
About this study
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.
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.
- Conditions
- Alkaptonuria
- Being tested
- Nitisinone
- Medical subject headings
- Alkaptonuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NitisinoneDrug
doses 1, 2, 4 \& 8 mg plus no treatment arm
| Study group | Role | What they receive |
|---|---|---|
| no treatment | No intervention | comparrator |
| Nitisinone 1mg | Experimental | interventional Receives: Drug: Nitisinone |
| Nitisinone 2mg | Experimental | interventional Receives: Drug: Nitisinone |
| Nitisinone 4mg | Experimental | interventional Receives: Drug: Nitisinone |
| Nitisinone 8mg | Experimental | interventional Receives: Drug: Nitisinone |
What is being measured
The primary outcome is the main question the study is designed to answer.
dose of nitisinone that decreases urinary homogentisic acid to near normal
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2013 (estimated)
- Study startMay 2013
- Primary completionOct 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for AlkaptonuriaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Liverpool
- Sponsor type
- University, hospital or other
- Collaborators
- Liverpool University Hospitals NHS Foundation Trust
- Responsible party
- Principal investigator, Professor Lakshminarayan Ranganath, University of Liverpool
- Investigators
- L Ranganath, Principal investigator, Royal Liverpool & Broadgreen University Hospitals NHS Truts
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01828463
- Sponsor's protocol ID
- UoL000928
- Acronym
- SONIA1
- Status last verified
- Jun 2014
- First submitted
- 5 Apr 2013
- Last updated
- 11 Jun 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Milan AM, Hughes AT, Davison AS, Khedr M, Rovensky J, Psarelli EE, Cox TF, Rhodes NP, Gallagher JA, Ranganath LR. Quantification of the flux of tyrosine pathway metabolites during nitisinone treatment of Alkaptonuria. Sci Rep. 2019 Jul 11;9(1):10024. doi: 10.1038/s41598-019-46033-x.
PubMed 31296884Ranganath LR, Milan AM, Hughes AT, Dutton JJ, Fitzgerald R, Briggs MC, Bygott H, Psarelli EE, Cox TF, Gallagher JA, Jarvis JC, van Kan C, Hall AK, Laan D, Olsson B, Szamosi J, Rudebeck M, Kullenberg T, Cronlund A, Svensson L, Junestrand C, Ayoob H, Timmis OG, Sireau N, Le Quan Sang KH, Genovese F, Braconi D, Santucci A, Nemethova M, Zatkova A, McCaffrey J, Christensen P, Ross G, Imrich R, Rovensky J. Suitability Of Nitisinone In Alkaptonuria 1 (SONIA 1): an international, multicentre, randomised, open-label, no-treatment controlled, parallel-group, dose-response study to investigate the effect of once daily nitisinone on 24-h urinary homogentisic acid excretion in patients with alkaptonuria after 4 weeks of treatment. Ann Rheum Dis. 2016 Feb;75(2):362-7. doi: 10.1136/annrheumdis-2014-206033. Epub 2014 Dec 4.
PubMed 25475116
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01828463
- Acronym / sponsor ID
- SONIA1 / UoL000928
- Conditions
- Alkaptonuria
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- University of LiverpoolUniversity, hospital or other
- Collaborators
- Liverpool University Hospitals NHS Foundation Trust
- Study start
- May 2013
- Primary completion
- Oct 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 10 Apr 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| no treatment | No intervention | –comparrator |
| Nitisinone 1mg | Experimental | Drug: Nitisinoneinterventional |
| Nitisinone 2mg | Experimental | Drug: Nitisinoneinterventional |
| Nitisinone 4mg | Experimental | Drug: Nitisinoneinterventional |
| Nitisinone 8mg | Experimental | Drug: Nitisinoneinterventional |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (24 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nitisinonedoses 1, 2, 4 \& 8 mg plus no treatment arm | Drug | Nitisinone 1mg, Nitisinone 2mg, Nitisinone 4mg, Nitisinone 8mg |
Primary outcome
dose of nitisinone that decreases urinary homogentisic acid to near normal
Time frame: 4 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2014.
- Derived from this study: PubMed 31296884Milan AM, Hughes AT, Davison AS, Khedr M, Rovensky J, Psarelli EE, Cox TF, Rhodes NP, Gallagher JA, Ranganath LR. Quantification of the flux of tyrosine pathway metabolites during nitisinone treatment of Alkaptonuria. Sci Rep. 2019 Jul 11;9(1):10024. doi: 10.1038/s41598-019-46033-x.
- Derived from this study: PubMed 25475116Ranganath LR, Milan AM, Hughes AT, Dutton JJ, Fitzgerald R, Briggs MC, Bygott H, Psarelli EE, Cox TF, Gallagher JA, Jarvis JC, van Kan C, Hall AK, Laan D, Olsson B, Szamosi J, Rudebeck M, Kullenberg T, Cronlund A, Svensson L, Junestrand C, Ayoob H, Timmis OG, Sireau N, Le Quan Sang KH, Genovese F, Braconi D, Santucci A, Nemethova M, Zatkova A, McCaffrey J, Christensen P, Ross G, Imrich R, Rovensky J. Suitability Of Nitisinone In Alkaptonuria 1 (SONIA 1): an international, multicentre, randomised, open-label, no-treatment controlled, parallel-group, dose-response study to investigate the effect of once daily nitisinone on 24-h urinary homogentisic acid excretion in patients with alkaptonuria after 4 weeks of treatment. Ann Rheum Dis. 2016 Feb;75(2):362-7. doi: 10.1136/annrheumdis-2014-206033. Epub 2014 Dec 4.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
L Ranganath principal investigator
Royal Liverpool & Broadgreen University Hospitals NHS Truts
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nitisinone in people with Alkaptonuria, run by University of Liverpool at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
dose of nitisinone that decreases urinary homogentisic acid to near normal (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01828463, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2014.