Results of the MOTION and SETTLE Trials Investigating the Use of Safinamide as Add-On Therapy to Dopamine Agonist and Levodopa

In the MOTION and SETTLE studies, safinamide was shown to be effective in the treatment of patients with Parkinson's disease (PD) as add-on therapy to a stable dose of a single dopamine agonist (DA) and as add-on therapy for patients taking levodopa, respectively, according to research presented at the 65^th Annual Meeting of the American Academy of Neurology.

Safinamide, a monoamine oxidase B (MAO-B) inhibitor with both dopaminergic and nondopaminergic mechanisms of action, has previously demonstrated efficacy in placebo-controlled trials at doses of 50-100mg/day as add-on therapy to DA-agonist in early nonfluctuating PD patients, and as add-on treatment to levodopa and other PD medications in PD patients with motor fluctuations in six-month treatment trials. Additional studies are ongoing investigating the potential use of safinamide in the treatment of epilepsy and restless legs syndrome.

In the MOTION study, Paulo Barone, MD, of the University of Salerno in Fisciano, Italy, and colleagues reported results from a 24-week randomized trial involving 607 patients with early idiopathic PD from North and South America, Europe, and India who were treated with a stable dose of a single dopamine agonist and either safinamide, 50 or 100 mg/day, or placebo.

Compared with placebo-treated patients, patients treated with safinamide, 100 mg/day, exhibited significantly improved Unified Parkinson's Disease Rating Scale (UPDRS) Part III and Parkinson's Disease Questionnaire (PDQ-39) scores and achieved a borderline statistically significant improvement in activities of daily living (100 mg/day) and UPDRS III (50 mg/day). Approximately 90% of patients completed the study, and common adverse events, occurring in 5% or more of patients, included arthralgia, dizziness, somnolence, headache, nausea, nasopharyngitis, and back pain.

In the SETTLE trial, Anthony Schapira, MD, of the University College of London in the United Kingdom, and colleagues reported results from a 24-week randomized trial involving 484 patients with PD and motor fluctuations from North America, Europe, and the Asia-Pacific region who were treated with levodopa and either safinamide, 50 to 100 mg/day, or placebo.

Compared with placebo-treated patients, safinamide (50-100 mg/day) significantly improved “ON” time (without worsening troublesome dyskinesia ), “OFF” time, UPDRS III, Clinical Global Impression—severity (CGI-S), Clinical Global Impression-Cognition (CGI-C), PDQ-39, and “OFF” time following the first morning levodopa dose. The authors also reported that safinamide significantly improved motor symptoms and patient quality of life vs. placebo as add-on to a single DA. Overall, 88% of patients completed the study, and the most common adverse events, occurring in 5% or more patients, included back pain, dyskinesia, fall, headache, nausea, and urinary tract infection.

“These results confirm the efficacy and good tolerability profile of safinamide 50 and 100 mg, already demonstrated in previous studies. Safinamide may be a new treatment option for patients with early PD who show signs of loss of benefit on DA-agonist monotherapy and for the treatment of PD patients treated with levodopa who continue to experience motor fluctuations ,” the authors concluded.

These studies were supported by Newron Pharmaceuticals/MerckSerono.