Efficacy and safety of once-daily nitisinone for patients with alkaptonuria (SONIA 2): an international, multicentre, open-label, randomised controlled trial.
Adult
Aged
Alkaptonuria
/ diagnosis
Cyclohexanones
/ administration & dosage
Drug Administration Schedule
Enzyme Inhibitors
/ administration & dosage
Female
Homogentisic Acid
/ metabolism
Humans
Internationality
Longitudinal Studies
Male
Middle Aged
Nitrobenzoates
/ administration & dosage
Single-Blind Method
Treatment Outcome
Journal
The lancet. Diabetes & endocrinology
ISSN: 2213-8595
Titre abrégé: Lancet Diabetes Endocrinol
Pays: England
ID NLM: 101618821
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
12
03
2020
revised:
28
05
2020
accepted:
02
06
2020
pubmed:
22
8
2020
medline:
2
9
2020
entrez:
22
8
2020
Statut:
ppublish
Résumé
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. 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-HGA 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-HGA 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. European Commission Seventh Framework Programme.
Sections du résumé
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-HGA
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-HGA
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.
FUNDING
European Commission Seventh Framework Programme.
Identifiants
pubmed: 32822600
pii: S2213-8587(20)30228-X
doi: 10.1016/S2213-8587(20)30228-X
pii:
doi:
Substances chimiques
Cyclohexanones
0
Enzyme Inhibitors
0
Nitrobenzoates
0
nitisinone
K5BN214699
Homogentisic Acid
NP8UE6VF08
Banques de données
ClinicalTrials.gov
['NCT01916382']
Types de publication
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
762-772Informations de copyright
Copyright © 2017 Elsevier Ltd. All rights reserved.