NCT01828463

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
40

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started May 2013

Shorter than P25 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 5, 2013

Completed
5 days until next milestone

First Posted

Study publicly available on registry

April 10, 2013

Completed
21 days until next milestone

Study Start

First participant enrolled

May 1, 2013

Completed
5 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2013

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2013

Completed
Last Updated

June 11, 2014

Status Verified

June 1, 2014

Enrollment Period

5 months

First QC Date

April 5, 2013

Last Update Submit

June 10, 2014

Conditions

Alkaptonuria

Outcome Measures

Primary Outcomes (1)

  • dose of nitisinone that decreases urinary homogentisic acid to near normal

    4 weeks

Study Arms (5)

no treatment

NO INTERVENTION

comparrator

Nitisinone 1mg

EXPERIMENTAL

interventional

Drug: Nitisinone

Nitisinone 2mg

EXPERIMENTAL

interventional

Drug: Nitisinone

Nitisinone 4mg

EXPERIMENTAL

interventional

Drug: Nitisinone

Nitisinone 8mg

EXPERIMENTAL

interventional

Drug: Nitisinone

Interventions

NitisinoneDRUG

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

Nitisinone 1mgNitisinone 2mgNitisinone 4mgNitisinone 8mg

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.
  • 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.
  • +7 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Royal Liverpool Hospital

Liverpool, Merseyside, L7 8XP, United Kingdom

Location

Related Publications (2)

  • 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.

    PMID: 31296884DERIVED

  • Ranganath 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.

    PMID: 25475116DERIVED

MeSH Terms

Conditions

Alkaptonuria

Interventions

nitisinone

Condition Hierarchy (Ancestors)

Amino Acid Metabolism, Inborn ErrorsMetabolism, Inborn ErrorsGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesMetabolic DiseasesNutritional and Metabolic Diseases

Study Officials

  • L Ranganath

    Royal Liverpool & Broadgreen University Hospitals NHS Truts

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Consultant in Metabolic medicine

Study Record Dates

First Submitted

April 5, 2013

First Posted

April 10, 2013

Study Start

May 1, 2013

Primary Completion

October 1, 2013

Study Completion

December 1, 2013

Last Updated

June 11, 2014

Record last verified: 2014-06

Locations

GB(1)