Details

Autor(en) / Beteiligte

• Ranganath, Lakshminarayan R
• Milan, Anna M
• Hughes, Andrew T
• Dutton, John J
• Fitzgerald, Richard
• Briggs, Michael C
• Bygott, Helen
• Psarelli, Eftychia E
• Cox, Trevor F
• Gallagher, James A
• Jarvis, Jonathan C
• van Kan, Christa
• Hall, Anthony K
• Laan, Dinny
• Olsson, Birgitta
• Szamosi, Johan
• Rudebeck, Mattias
• Kullenberg, Torbjörn
• Cronlund, Arvid
• Svensson, Lennart
• Junestrand, Carin
• Ayoob, Hana
• Timmis, Oliver G
• Sireau, Nicolas
• Le Quan Sang, Kim-Hanh
• Genovese, Federica
• Braconi, Daniela
• Santucci, Annalisa
• Nemethova, Martina
• Zatkova, Andrea
• McCaffrey, Judith
• Christensen, Peter
• Ross, Gordon
• Imrich, Richard
• Rovensky, Jozef

Titel

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

Ist Teil von

• Annals of the rheumatic diseases, 2016-02, Vol.75 (2), p.362-367

Ort / Verlag

England: BMJ Publishing Group LTD

Erscheinungsjahr

2016

Quelle

BMJ Journals Archiv - DFG Nationallizenzen

Beschreibungen/Notizen

• BackgroundAlkaptonuria (AKU) is a serious genetic disease characterised by premature spondyloarthropathy. Homogentisate-lowering therapy is being investigated for AKU. Nitisinone decreases homogentisic acid (HGA) in AKU but the dose-response relationship has not been previously studied.MethodsSuitability Of Nitisinone In Alkaptonuria 1 (SONIA 1) was an international, multicentre, randomised, open-label, no-treatment controlled, parallel-group, dose-response study. The primary objective was to investigate the effect of different doses of nitisinone once daily on 24-h urinary HGA excretion (u-HGA24) in patients with AKU after 4 weeks of treatment. Forty patients were randomised into five groups of eight patients each, with groups receiving no treatment or 1 mg, 2 mg, 4 mg and 8 mg of nitisinone.FindingsA clear dose-response relationship was observed between nitisinone and the urinary excretion of HGA. At 4 weeks, the adjusted geometric mean u-HGA24 was 31.53 mmol, 3.26 mmol, 1.44 mmol, 0.57 mmol and 0.15 mmol for the no treatment or 1 mg, 2 mg, 4 mg and 8 mg doses, respectively. For the most efficacious dose, 8 mg daily, this corresponds to a mean reduction of u-HGA24 of 98.8% compared with baseline. An increase in tyrosine levels was seen at all doses but the dose-response relationship was less clear than the effect on HGA. Despite tyrosinaemia, there were no safety concerns and no serious adverse events were reported over the 4 weeks of nitisinone therapy.ConclusionsIn this study in patients with AKU, nitisinone therapy decreased urinary HGA excretion to low levels in a dose-dependent manner and was well tolerated within the studied dose range.Trial registration numberEudraCT number: 2012-005340-24. Registered at ClinicalTrials.gov: NCTO1828463.