Date: 2013-03-18
Type of information:
phase: 3
Announcement: presentation of results at the 65rd AAN Annual Meeting:
" Safinamide as an Add-On Therapy to a Stable Dose of a Single Dopamine Agonist: Results from a Randomized, Placebo-Controlled, 24-Week Multicenter Trial in Early Idiopathic Parkinson Disease (PD) Patients (MOTION Study)" and "Safinamide Add on to L-Dopa: A Randomized, Placebo-Controlled, 24-Week Global Trial in Patients with Parkinson's Disease (PD) and Motor Fluctuations (SETTLE)"
Company: Newron Pharmaceuticals (Italy)
Product: safinamide
Action mechanism: Safinamide is an alpha-aminoamide is currently being developed by Newron as an add-on therapy to dopamine agonists or to levodopa in patients with early or mid- to late-stage Parkinson’s disease (PD). It is believed to have both dopaminergic and non-dopaminergic activities, including selective and reversible inhibition of monoamine oxidase B (MAO-B), activity-dependent sodium channel antagonism and inhibition of glutamate release in vitro.
Disease: Parkinson's disease
Therapeutic area: Neurodegenerative diseases - CNS diseases
Country:
Trial
details: The MOTION (SafinaMide add-On To dopamine agonist for early Idiopathic ParkinsON’s disease with motor fluctuations) study is a six-month (24-week), randomized, double-blind, placebo-controlled international Phase III trial. It enrolled 679 patients with early idiopathic Parkinson’s disease (less than five years of disease duration) treated with a stable dose of a single dopamine agonist for at least four weeks. Study participants were randomized equally to receive once daily safinamide 50 mg, or 100 mg, or matching placebo tablets as adjunctive treatment to a single dopamine agonist at a fixed dose. In accordance with international regulatory guidelines, the primary endpoint of the trial was the change in motor symptoms assessed by the change in the Unified Parkinson’s Disease Rating Scale (UPDRS) Part III score from baseline to week 24.
The SETTLE (SafinamidE Treatment as add-on To LEvodopa in idiopathic Parkinson’s disease with motor fluctuations)study is a six-month (24-week), randomized, double-blind, placebo-controlled international Phase III trial. It enrolled 549 patients with mid- to late-stage idiopathic Parkinson’s disease (more than three years of disease duration) treated with a stable dose of levodopa for at least four weeks, who have motor fluctuations with more than one and a half hours of “OFF” time during the day. Additionally, patients may be receiving concomitant treatment with stable doses of a dopamine agonist, a COMT inhibitor, an anticholinergic and/or amantadine. After a four-week levodopa dosage stabilization phase, study participants were randomized in one of the two arms of the trial (1:1) to receive either safinamide or matching placebo tablets, as adjunctive treatment. Based on discussions with the regulatory authorities, and current guidelines, the primary endpoint of the trial was the change in daily “ON” time, as assessed by the recordings of diary cards maintained by patients after prior training, from baseline to week 24.
The MOTION and SETTLE studies are part of the clinical development program of safinamide in Parkinson’s disease, together with completed placebo-controlled studies 009, 015, 016, 017 and 018. This clinical program is designed to investigate safinamide as an add-on therapy to dopamine agonist therapy in patients with early Parkinson’s disease and as an add-on to levodopa therapy in patients with advanced Parkinson’s disease.
Latest
news: * On March 18, 2013, Newron Pharmaceuticals and its partner Zambon have announced that results from the Phase III studies MOTION and SETTLE have been presented at the 65th Annual Meeting of the American Academy of Neurology (AAN) taking place from March 16–23, 2013, at the San Diego Convention Center, San Diego, CA, USA. Safinamide Phase III development as add-on treatment to dopamine agonist or levodopa in early to late stage Parkinson’s disease (PD) has been completed. MOTION* study was a six-month (24-week), randomized, double-blind, placebo-controlled international Phase III trial. Safinamide was very well tolerated. 607 patients completed the trial; the drop-out rate was similar in all three treatment groups (approx. 11%). The most commonly reported adverse events were nausea, dizziness, somnolence, headache and back pain, with no significant difference in the incidence of any of these events among treatment groups. Similarly, the incidence of treatment induced abnormalities in laboratory results, ophthalmological examinations, vital signs and ECG was similar in all groups. SETTLE** study was a six-month (24-week), randomized, double-blind, placebo-controlled international Phase III trial. Safinamide was very well tolerated. 484 patients completed the trial; the drop-out rate was similar in both treatment groups (approx. 12%). The most commonly reported adverse events were nausea, urinary tract infections, falls, back pain and dyskinesia. Transient dyskinesia occurred more frequently with safinamide, but was mainly mild, and was not associated with treatment discontinuation. Similarly, the incidence of treatment induced abnormalities in laboratory results, ophthalmological examinations, vital signs and ECG was similar in all groups. Safinamide filing for regulatory approval as add-on in early and mid-to late Parkinson's disease patients in EU and US is expected in Q4/2013. * On May 14, 2012, Newron Pharmaceuticals, an italian research and development company focused on novel CNS and pain therapies, has announced the top line results from the last two phase III studies of safinamide as an add-on treatment in both early (MOTION) and advanced (SETTLE) Parkinson's disease patients.
Analyses (On treatment, ANCOVA-LOCF) performed in the ITT population and the modified dopamine agonist monotherapy population (excluding 13 patients not meeting the major inclusion criteria of stable, dopamine agonist monotherapy) provided similar results. Treatment with safinamide 100 mg/day, compared with dopamine agonist alone (=placebo), improved the UPDRS III total score (change from base line to endpoint) by 1.04 ± 0.58 (p=0.07) and 1.20 ± 0.58 (p=0.039) in the ITT and modified dopamine agonist monotherapy population, respectively. Significant benefits of safinamide 100 mg/day were also noted in the PDQ39 (Parkinson’s Disease Quality of Life) and EQ-5D (European Quality of Life 5 domains).
Analyses (On treatment, ANCOVA-LOCF) performed in the ITT population showed treatment with safinamide 50-100 mg/day significantly improved ON-Time without troublesome dyskinesia compared to placebo by 0.96 ± 0.21 hours (p<0.01) in the ITT. Significant benefits of safinamide 50-100 mg/day were also reported in OFF-time, Motor symptoms (UPDRS III), PDQ39, EQ-5D, clinical global impression of change and severity, and OFF-time post morning dose of levodopa.
The results from both MOTION and SETTLE studies were consistent with the positive pattern of efficacy and safety reported in previous phase II/III studies in early (studies 009 and 015) and advanced (study 016) Parkinson\'s disease. Safinamide benefits were evident on primary and secondary measures. The safety results indicated that safinamide was very well tolerated with no significant difference in the incidence of drop outs, serious adverse events, treatment emergent adverse events, laboratory abnormalities and ophthalmologic findings between safinamide and placebo treated patients. A full analysis of the data will be presented at upcoming scientific meetings.
The worldwide rights to develop, manufacture and commercialize safinamide in Parkinson’s disease, Alzheimer’s disease and other therapeutic applications, had been returned to Newron by Merck Serono, the division for biopharmaceuticals of German company Merck KGaA on April 17, 2012.
