Adjunctive Safinamide Increases On Time in Parkinson's Disease
Patients with Parkinson’s disease often experience “off” periods where symptoms reemerge.
The addition of safinamide to levodopa therapy for Parkinson's disease (PD) increases “on” time without troublesome dyskinesia, according to results of a randomized clinical trial published in JAMA Neurology.1 The investigators, led by Anthony Schapira, MD, of the University College London Institute of Neurology, concluded that safinamide is a safe and effective adjunct to levodopa in patients with PD and motor fluctuations.
The 24-week clinical trial enrolled 549 PD patients (mean age= 61 +/- 9 years) from 119 centers. Participants were randomly assigned to receive either safinamide (n= 274) or placebo (n=275). Patients on active drug were started on a dose of 50 mg/d of safinamide and increased to 100 mg/d if therapy was well tolerated by day 14. At baseline, all participants had an average of >1.5 hours of “off” time despite levodopa therapy (mean dose= 776.8 mg/d), during which they experienced dyskinesias. The majority (74.3%, n= 408) were also on dopamine agonist therapy, while amantadine, anticholinergics, and entacapone were adjunctively being taken by 30.2%, 17.3%, and 15.1% of patients, respectively. Changes in therapy during the study were nearly twice as frequent in the placebo group (7.6%, 21 patients) compared with the safinamide group (4.0%, 11 patients).
At the end of 6 months, safinamide increased total daily “on” time without troublesome dyskinesia by a mean of +1.42 (2.80) hours compared to +0.52 (2.47) hours with placebo. Safinamide also showed modest benefits in 18 patients (6.6%) compared with 4 patients (1.5%) taking placebo in secondary measures including Clinical Global Impression Change (CGI-C), Patient Global Impression Change (PGI-C), Clinical Global Impression Severity (CGI-S), and EuroQoL5 dimensions (EQ-5D) index scores, as well as time “off” after morning levodopa dose and total levodopa dose. Complications to therapy as measured by Unified Parkinson's Disease Rating Scale (UPDRS) Part IV scores were mildly worsened (+0.1 points) with safinamide.
A total of 245 patients (89.4%) in the safinamide group and 241 patients (87.6%) in the placebo group completed the study. The main reason for discontinuation was for treatment-emergent adverse events (TEAEs) reported by 12 safinamide patients and 10 taking placebo (4.4% and 3.6%, respectively). Serious adverse events (SAEs) related to treatment were reported more frequently in the placebo group than those taking safinamide (9.5% vs 6.6%), although the emergence of dyskinesia occurred more frequently with safinamide than placebo (14.6% vs 5.5%). One death occurred in the safinamide group (deemed unlikely to be related to treatment) and 2 in the placebo group.
The results of the Safinamide Treatment as Add-on to Levodopa study showed clear benefit for this treatment in increasing “on” time to levodopa without troublesome dyskinesia. This supports results from a preclinical study indicating that safinamide reduced the intensity and duration of dyskinesias and prolonged the motor effects of levodopa in monkeys.2 Both studies suggest that safinamide is a safe and effective adjunctive therapy to stable dose levodopa for PD.
- Schapira AHV, Fox SH, Hauser RA, et al. Assessment of safety and efficacy of safinamide as a levodopa adjunct in patients with Parkinson Disease and motor fluctuations. JAMA Neurol. 2016. doi:10.1001/jamaneurol.2016.4467
- Gregoire L, Jourdain VA, Townsend M, et al. Safinamide reduces dyskinesias and prolongs L-DOPA antiparkinsonian effect in parkinsonian monkeys. Parkinsonism Relat Disord. 2013;19:508-514.