Naftazone in advanced Parkinson's disease: An acute L-DOPA challenge randomized controlled trial. (March 2019)

• Record Type: Journal Article
• Authors: Corvol, Jean-Christophe; Durif, Franck; Meissner, Wassilios G.; Azulay, Jean-Philippe; Haddad, Raphaël; Guimarães-Costa, Raquel; Mariani, Louise-Laure; Cormier-Dequaire, Florence; Thalamas, Claire; Galitzky, Monique; Boraud, Thomas; Debilly, Bérengère; Eusebio, Alexandre; Houot, Marion; Dellapina, Estelle; Chaigneau, Véronique; Salis, Alexandrine; Lacomblez, Lucette; Benel, Laurent; Rascol, Olivier
• Is Part Of: Parkinsonism & related disorders. Volume 60(2019)
• Page Start: 51
• Page End: 56
• Publication Date: 2019-03
• Subjects: Parkinson's disease -- Naftazone -- Levodopa-induced dyskinesia -- Clinical trial; Parkinson's disease -- Periodicals; Movement disorders -- Periodicals; Movement Disorders -- Periodicals; Nerve Degeneration -- Periodicals; Nervous System Diseases -- Periodicals; Parkinson Disease -- Periodicals; Tremor -- Periodicals; Parkinson, Maladie de -- Périodiques; Parkinson's disease; 616.833
• DOI: 10.1016/j.parkreldis.2018.10.005
• Languages: English
• ISSNs: 1353-8020

Abstract

Abstract: Introduction: There is an unmet need to better control motor complications in Parkinson's disease (PD). Naftazone, which exhibits glutamate release inhibition properties, has shown antiparkinsonian and antidyskinetic activity in preclinical models of PD and in a clinical proof of concept study. Methods: We conducted a double-blind randomized placebo-controlled cross-over trial in PD patients with motor fluctuations and dyskinesia testing naftazone 160 mg/day versus placebo for 14 days. The two co-primary endpoints were the area under curve (AUC) of motor (MDS-UPDRS part III) and dyskinesia (AIMS) scores during an acute levodopa challenge performed at the end of each period. Secondary endpoints were UDysRS and axial symptoms scores during the challenge; AIMS, UDysRS, and time spent with or without dyskinesia the day before the challenge. The primary analysis was performed in the per protocol population. Results: Sixteen patients were included in the analysis. There was no difference between naftazone and placebo for the AUC of MDS-UPDRS III (−89, 95%CI[-1071; 893], p = 0.85), and AIMS (70, 95%CI[-192; 332], p = 0.57). At the end of treatment periods, AIMS score tended to be lower with naftazone than placebo (4.4 ± 3.4 versus 6.7 ± 4.4, p = 0.07), but UDysRS scores and other secondary outcomes were not different. Naftazone was safe and well tolerated. Conclusions: This study did not confirm previous results on the efficacy of naftazone on dyskinesia nor motor fluctuations highlighting the problem of translating results obtained in preclinical models into clinical trials. Further investigation of naftazone may be conducted in PD with longer treatment duration. Highlights: There is an unmet need to better control motor complications in Parkinson's disease. Naftazone has antiparkinsonian and antidyskinetic activity in preclinical models. We conducted a cross-over trial testing naftazone versus placebo in advanced PD. This trial failed to confirm previous results on the efficacy of naftazone.