Objective:

To investigate the efficacy of safinamide, compared to placebo, as add-on therapy to stable doses of levodopa, on both motor and non-motor symptoms in fluctuating Parkinson’s Disease (PD) patients.

Background: Chronic levodopa treatment is associated with motor complications and non-motor symptoms. Glutamate has been implicated in the neural mechanism undelying the development of these phenomena. Safinamide (Xadago^®, Zambon SpA Italy) has a unique dopaminergic and non-dopaminergic mode of action that includes the enhancement of the dopaminergic transmission through the selective and reversible inhibition of the monoamine-oxidase B enzyme, and the control of the abnormal glutamate release through the state- and use-dependent blockade of the sodium channels. It has therefore the potential to improve both motor and non-motor symptoms.

Methods:

The effects of safinamide on motor complications and on non-motor symptoms were investigated using the data from studies 016, 018 and SETTLE.  Studies 016 and SETTLE were 6-month, double-blind, placebo-controlled trials comparing safinamide versus placebo as adjunct therapy to levodopa (alone or with other antiparkinson drugs) in fluctuating PD patients. Study 018 was the 18-month extension of trial 016. Data from studies 016 and SETTLE were combined to analyze motor fluctuations and pain, while data from study 018 were used to analyze dyskinesia.

Results:

Safinamide significantly improved motor fluctuations, dyskinesia and pain in PD patients, irrespective of whether or not other drugs were added to the baseline levodopa treatment, thus suggesting that could be considered either as a first adjunct medication in PD patients not sufficiently controlled on levodopa, and as an add-on in patients already taking levodopa and other concomitant dopaminergic medications.  

Conclusions: Safinamide, administered as add-on therapy in fluctuating PD patient, improved motor complication and non-motor symptoms without increasing troublesome dyskinesia, maintaning the benefits in the long-term with a significant improvement of patients’ quality of life. These favourable effects may be explained by its modulation of glutamatergic hyperactivity. 

References: Cattaneo C., La Ferla R., Bonizzoni E., Sardina M. Long-term effects of safinamide on dyskinesia in mid- to late-stage Parkinson’s Disease: a post-hoc analysis. J Parkinsons Dis 2015; 5(3): 475-481 Cattaneo C., Sardina M., Bonizzoni E. Safinamide as add-on therapy to levodopa in mid- to late-stage Parkinson’s Disease fluctuating patients: post-hoc analyses of studies 016 and SETTLE. J Parkinsons Dis 2016; 6(1): 165-173

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MDS Abstracts - https://www.mdsabstracts.org/abstract/safinamide-improves-both-motor-and-non-motor-symptoms-in-fluctuating-parkinsons-disease-patients/