Melevodopa/Carbidopa Effervescent Formulation in the Treatment of Motor Fluctuations in Advanced Parkinson’s Disease Fabrizio Stocchi, MD, PhD, 1 * Mario Zappia, MD, 2 Valentina Dall’Armi, MSc, 3 Jaime Kulisevsky, MD, 4 Paolo Lamberti, MD, 5 and Jose ´ Angel Obeso, MD, 6 on behalf of the Melevodopa Plus Carbidopa Study Group 1 Department of Neuroscience, Institute of Neurology, IRCCS San Raffaele Pisana, Roma 00163, Italy 2 Neuroscience Department, University of Catania, Catania 95123, Italy 3 Department of Clinical and Molecular Epidemiology, IRCCS San Raffaele Pisana, Roma 00163, Italy 4 Neurology Department, Movement Disorders Unit, Fundacio´de G. S. de l’Hospital de la Santa Creu Sant Pau, Barcelona, Spain 5 Department of Neurology, Ospedale Policlinico Consorziale, Bari 70124, Italy 6 Department of Neurology, Neurology, Clinica Universitaria de Navarra, Pamplona 31008, Spain Abstract: Melevodopa hydrochloride plus carbidopa in effer- vescent tablets (M/C) is a readily soluble antiparkinsonian tablet formulation. A total of 221 patients with Parkinson’s disease and motor fluctuations entered a randomized, double- blind, double-dummy, controlled parallel group study, which compared the effectiveness of oral M/C effervescent tablets with standard oral formulation levodopa/carbidopa tablets (L/C; Sinemet) in reducing total daily OFF time. The dif- ference of total daily OFF time (intention-to-treat popula- tion) between the two groups was not statistically signifi- cant (P 5 0.07): 239.4 minutes (95%CI: 267.08 to 211.73) in M/C group vs. 13.5 minutes (95%CI: 236.19 to 143.26) in the L/C group. In the intragroup analysis, M/C signifi- cantly reduced the baseline daily OFF, which remained unchanged in the L/C group. There were no unexpected adverse events in either treatment arms, and discontinuation rates due to adverse events did not differ between the two groups [M/C: 2 patients (1.3%); L/C: 1 patient (1.4%)]. This study failed to meet the primary endpoint (P 5 0.07); how- ever, there was a trend in favour of the M/C preparation, which deserves further attention. Ó 2010 Movement Disor- der Society Key words: melevodopa; levodopa methylester; motor fluctuations; Parkinson’s disease; liquid formulation Levodopa combined with a peripheral dopa decar- boxylase inhibitor, carbidopa or benserazide, remains irreplaceable in the treatment of Parkinson’s disease (PD). 1 Unfortunately, the majority of treated patients de- velop motor complications, and the duration of benefit following a given dose of L-dopa becomes progressively shorter, gradually mirroring the plasma half-life of L-dopa. At this point, factors interfering with L-dopa delivery and absorption may induce motor fluctuations. 2–6 To reach its site of absorption in the small intestine, orally administered L-dopa has to pass through the stomach 7,8 and, thus, has to rely on gastric emptying, which is often delayed in PD patients due to the dis- ease itself, the effects of PD drugs, and dietary intake. 9,10 Another problem that hinders optimal absorption of oral L-dopa is its poor solubility when formulated as a tablet. 8 Compared with conventional See appendix for a complete list of participating investigators. Potential conflict of interest: This trial was a trial sponsored by Chiesi pharma Italy. F.S. and J.O. has served as a paid consultant for Chiesi pharma. The authors have complied with all rules regarding journal ghost-writing policies. The manuscript has been written by the authors, no ghost writer has been employed in preparing the manuscript. All the authors, but Valentina Dall’Armi, received a research grant from Chiesi Pharma for the conduction of the study. *Correspondence to: Dr. Fabrizio Stocchi, Institute of Neurology, IRCCS San Raffaele, Via della Pisana 235, 00163 Roma, Italy. E-mail: fabrizio.stocchi@fastwebnet.it Received 26 January 2009; Revised 30 October 2009; Accepted 30 March 2010 Published online 28 July 2010 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/mds.23206 Movement Disorders Vol. 25, No. 12, 2010, pp. 1881–1887 Ó 2010 Movement Disorder Society 1881