A proof-of-concept, randomized, placebo-controlled, multiple cross-overs (n-of-1) study of naftazone in Parkinson's disease.

Abstract

To explore for the first time the tolerability and efficacy of naftazone in patients with Parkinson's disease (PD). Proof-of-concept, randomized, double-blind, placebo-controlled, multiple-cross-over n-of-1 study in patients with PD with wearing-off and dyskinesias. Naftazone was titrated up to 120 mg/day during an initial single-blind dose-finding phase. Seven patients entered the placebo-controlled phase (four consecutive 28-day cross-overs). Three outcome measures were used to collect preliminary indices of efficacy: (i) 48-h ON-OFF diaries; (ii) Unified PD Rating Scale (UPDRS) part III while ON; (iii) seven-point Likert scale to assess "patients' discomfort caused by dyskinesias" (Q1) and 'disability during OFF-periods' (Q2). A 'responder' analysis (proportion of patients with mean treatment effect [naftazone minus placebo] favoring naftazone over the 4 cross-over periods) was used. Treatment effects were derived from mixed-effects anova. On diaries, 5/7 patients responded to naftazone for 'ON-time with troublesome dyskinesia' (reduced time, treatment effect: -49 [95% CI: -93/-4] min, P = 0.03), 6/7 regarding 'ON-time without troublesome dyskinesia' (increased time, treatment effect: 35 [-19/88], P = 0.2). No trend was observed for 'OFF' time. There were 7/7 'responders' regarding UPDRSIII (reduced score, treatment effect: -2.1[-4.5/0.2], P = 0.08). The 7-point scales did not show clear trends in favor of naftazone (3/7 responders for Q1 and 4/7 for Q2). Four of the seven patients reported adverse events after randomization, mostly related to the CNS (mild: 2, severe: 2). These pilot findings are consistent with preclinical data in primates and support the hypothesis that naftazone may have antiparkinsonian and antidyskinetic effects in humans that deserve further clinical investigation.

• Authors: Olivier Rascol, Joaquim Ferreira, Laurence Nègre-Pages, Santiago Perez-Lloret, Lucette Lacomblez, Monique Galitzky, Jean-Christophe Lemarié, Jean-Christophe Corvol, Jonathan M Brotchie, Laura Bossi
• Journal: Fundamental & clinical pharmacology (Fundam Clin Pharmacol) Vol. 26 Issue 4 Pg. 557-64 (Aug 2012) ISSN: 1472-8206 [Electronic] England
• PMID: 21585523 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: © 2011 The Authors Fundamental and Clinical Pharmacology © 2011 Société Française de Pharmacologie et de Thérapeutique.

Chemical References

• Antiparkinson Agents
• Naphthoquinones
• Placebos
• naftazone

Topics

• Aged
• Antiparkinson Agents (adverse effects, therapeutic use)
• Cross-Over Studies
• Double-Blind Method
• Dyskinesias (drug therapy)
• Female
• Humans
• Male
• Naphthoquinones (adverse effects, therapeutic use)
• Parkinson Disease (drug therapy)
• Pilot Projects
• Placebos
• Single-Blind Method
• Treatment Outcome