Naftazone in advanced Parkinson’s disease: An acute L-DOPA challenge randomized controlled trial
Parkinsonism & Related Disorders. 2018-10-01; :
DOI: 10.1016/j.parkreldis.2018.10.005
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1. Parkinsonism Relat Disord. 2018 Oct 4. pii: S1353-8020(18)30431-0. doi:
10.1016/j.parkreldis.2018.10.005. [Epub ahead of print]
Naftazone in advanced Parkinson’s disease: An acute L-DOPA challenge randomized
controlled trial.
Corvol JC(1), Durif F(2), Meissner WG(3), Azulay JP(4), Haddad R(5),
Guimarães-Costa R(6), Mariani LL(6), Cormier-Dequaire F(6), Thalamas C(7),
Galitzky M(7), Boraud T(3), Debilly B(2), Eusebio A(4), Houot M(8), Dellapina
E(7), Chaigneau V(7), Salis A(7), Lacomblez L(6), Benel L(5), Rascol O(7); French
NS-Park/F-CRIN Network.
Author information:
(1)Sorbonne Université, INSERM UMRS 1127 and CIC-1422, CNRS UMR, 7225, ICM,
Assistance Publique Hôpitaux de Paris, CHU Pitié-Salpêtrière, Department of
Neurology, Paris, France. Electronic address: .
(2)Department of Neurology, CHU Clermont-Ferrand, UFR Medicine, EA 7980,
University Clermont Auvergne, Clermont-Ferrand, France.
(3)Service de Neurologie, IMNc, CHU Bordeaux, 33000, Bordeaux, France; Univ. de
Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux,
France.
(4)Aix Marseille Univ, APHM, CNRS, UMR 7289, Hôpital de la Timone, Department of
Neurology and Movement Disorders, Marseille, France.
(5)Clevexel Pharma SA, Paris, France.
(6)Sorbonne Université, INSERM UMRS 1127 and CIC-1422, CNRS UMR, 7225, ICM,
Assistance Publique Hôpitaux de Paris, CHU Pitié-Salpêtrière, Department of
Neurology, Paris, France.
(7)Clinical Investigation Center CIC-1436, Departments of Clinical Pharmacology
and Neurosciences, University Hospital of Toulouse, INSERM, University of
Toulouse 3, Toulouse, France; F-CRIN, UMS 015, Toulouse, France.
(8)Institute of Memory and Alzheimer’s Disease (IM2A), Centre of Excellence of
Neurodegenerative Disease (CoEN), ICM, CIC Neurosciences, APHP Department of
Neurology, Hopital Pitié-Salpêtrière, University Paris 6, Paris, France.
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.
Copyright © 2018 Elsevier Ltd. All rights reserved.
DOI: 10.1016/j.parkreldis.2018.10.005
PMID: 30297210