Summary of project PR001471
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001471. The data can be accessed directly via it's Project DOI: 10.21228/M8KH70 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001471 |
| Project DOI: | doi: 10.21228/M8KH70 |
| Project Title: | Metabolomic analysis in SONIA 2, a phase 3 international randomised-controlled trial of nitisinone in alkaptonuria (AKU) |
| Project Summary: | Abstract from main SONIA 2 publication: Background Alkaptonuria is a rare, genetic, multisystem disease characterised by the accumulation of homogentisic acid (HGA). No HGA-lowering therapy has been approved to date. The aim of SONIA 2 was to investigate the efficacy and safety of once-daily nitisinone for reducing HGA excretion in patients with alkaptonuria and to evaluate whether nitisinone has a clinical benefit. Methods SONIA 2 was a 4-year, open-label, evaluator-blind, randomised, no treatment controlled, parallel-group study done at three sites in the UK, France, and Slovakia. Patients aged 25 years or older with confirmed alkaptonuria and any clinical disease manifestations were randomly assigned (1:1) to receive either oral nitisinone 10 mg daily or no treatment. Patients could not be masked to treatment due to colour changes in the urine, but the study was evaluator-blinded as far as possible. The primary endpoint was daily urinary HGA excretion (u-HGA24) after 12 months. Clinical evaluation Alkaptonuria Severity Score Index (cAKUSSI) score was assessed at 12, 24, 36, and 48 months. Efficacy variables were analysed in all randomly assigned patients with a valid u-HGA24 measurement at baseline. Safety variables were analysed in all randomly assigned patients. The study was registered at ClinicalTrials.gov (NCT01916382). Findings Between May 7, 2014, and Feb 16, 2015, 139 patients were screened, of whom 138 were included in the study, with 69 patients randomly assigned to each group. 55 patients in the nitisinone group and 53 in the control group completed the study. u-HGA24 at 12 months was significantly decreased by 99·7% in the nitisinone group compared with the control group (adjusted geometric mean ratio of nitisinone/control 0·003 [95% CI 0·003 to 0·004], p<0·0001). At 48 months, the increase in cAKUSSI score from baseline was significantly lower in the nitisinone group compared with the control group (adjusted mean difference –8·6 points [–16·0 to –1·2], p=0·023). 400 adverse events occurred in 59 (86%) patients in the nitisinone group and 284 events occurred in 57 (83%) patients in the control group. No treatment-related deaths occurred. Interpretation Nitisinone 10 mg daily was well tolerated and effective in reducing urinary excretion of HGA. Nitisinone decreased ochronosis and improved clinical signs, indicating a slower disease progression. |
| Institute: | University of Liverpool Institute of Life Course & Medical Sciences |
| Department: | Department of Musculoskeletal & Ageing Science |
| Last Name: | Brendan |
| First Name: | Norman |
| Address: | William Henry Duncan Building, 6 West Derby Street, Liverpool, UK. L7 8TX |
| Email: | bnorman@liverpool.ac.uk |
| Phone: | +447809606497 |
| Funding Source: | European Commission for the Framework 7 grant award (DevelopAKUre, project number: 304985), Alkaptonuria Society (BPN is funded by the Alkaptonuria Society through a Sireau Fellowship Award). |
Summary of all studies in project PR001471
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002296 | Comprehensive biotransformation analysis of phenylalanine-tyrosine metabolism reveals alternative routes of metabolite clearance in nitisinone-treated alkaptonuria (Serum metabolomic analysis) | Homo sapiens | University of Liverpool Institute of Life Course & Medical Sciences | MS | 2022-10-14 | 1 | 276 | Uploaded data (400.2G)* |
| ST002297 | Comprehensive biotransformation analysis of phenylalanine-tyrosine metabolism reveals alternative routes of metabolite clearance in nitisinone-treated alkaptonuria (Urine metabolomic analysis) | Homo sapiens | University of Liverpool Institute of Life Course & Medical Sciences | MS | 2022-10-14 | 1 | 309 | Uploaded data (319.3G)* |
