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

Background: Studies 016 and SETTLE showed that safinamide was safe and effective as adjunct therapy in patients with advanced Parkinson's disease (PD) and motor fluctuations. The addition of safinamide to a stable dose of levodopa alone or with other antiparkinsonian medications significantly increased ON time with no/non-troublesome dyskinesia, decreased OFF time and improved Parkinson's symptoms. Objective: To evaluate the clinical effects of safinamide 100 mg/day on motor fluctuations and cardinal Parkinson's symptoms in specific patient subgroups using pooled data from Studies 016 and SETTLE. Methods: Both studies were double blind, placebo-controlled, randomized, phase 3 trials which enrolled patients with midto late-stage PD experiencing motor fluctuations while receiving optimized and stable doses of levodopa, alone or with other dopaminergic treatments. The present post-hoc analyses assessed the change from baseline in ON time (with no or non-troublesome dyskinesia) and OFF time in subgroups of patients who were receiving only levodopa at baseline, who were classified as mild fluctuators (daily OFF time <= 4 h), and who were receiving concomitant dopaminergic therapy, with or without amantadine, and the effects of safinamide versus placebo on individual cardinal PD symptoms during ON time. Results: Safinamide significantly increased mean ON time (with no or non-troublesome dyskinesia) and reduced mean OFF time when used as first adjunct therapy in levodopa-treated patients and patients with mild motor fluctuations. Mean daily ON time (with no or non-troublesome dyskinesia) and OFF time were favorably changed, compared with placebo, to similar extents regardless of whether patients were receiving concomitant dopamine agonists, catechol-O-methyltransferase inhibitors and amantadine. Additionally, safinamide improved bradykinesia, rigidity, tremor and gait. Conclusions: Safinamide was a safe and effective first adjunct therapy in levodopa-treated patients and improved 4/5 cardinal symptoms of PD while providing benefits to mild and non-mild fluctuators and patients receiving other concomitant dopaminergic therapies.