Date: 2013-06-19
Type of information:
phase: 3
Announcement: presentation of phase 3 studies at the 17th International Congress of Parkinson’s disease and Movement Disorders, taking place from June 16 to 20, 2013, at the Sydney Convention and Exhibition Centre, Sydney, Australia.Abstracts• “Safinamide significantly improves responder rates in fluctuating PD patients as add-on to levodopa (SETTLE)”, abstract no. 424• “Safinamide is associated with clinically important improvement in motor symptoms in fluctuating PD patients as add-on to levodopa (SETTLE)”, abstract no. 422
Company: Newron Pharmaceuticals (Italy) Zambon (Italy)
Product: safinamide
Action mechanism: Safinamide, 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. 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 earlyParkinson’s disease and as an add-on to levodopa therapy in patients with advanced Parkinson’s disease.
Latest
news: * On June 19, 2013, Newron Pharmaceuticals and its partner Zambon have presented results from SETTLE Phase III study with safinamide at the 17th International Congress of Parkinson’s disease and Movement Disorders. Results presented showed that in the SETTLE study safinamide significantly improved “super responder“ rates in fluctuating PD patients as add-on to levodopa and other dopaminergic therapies. Safinamide was also associated with clinically important improvement in motor symptoms in fluctuating PD patients as add-on to levodopa and other dopaminergic therapies. The results indicate a magnitude of benefit with safinamide which is of clinical relevance, i.e improvements of more than one hour in the patient and caregiver-rated ON and OFF time plus 30 per cent or greater improvement in motor symptoms (UPDRS Part III, as rated by a neurologist) in a significantly (p=0.018) larger proportion of patients than standard of care. In addition, safinamide shows a very rapid onset of efficacy with significant improvements being observed in ON-time (p=0.0003) and OFF-time (p<.0001) from week two onwards.
These results will be part of the regulatory submission planned to be filed in Europe and USA in QIV/2013.* On June 12, 2013, Newron Pharmaceuticals, a R&D company focused on novel CNS and pain therapies, and its partner Zambon, a pharmaceutical company strongly committed in the respiratory, primary care and CNS therapeutic area, have announced that additional results from the safinamide Phase III studies will be presented at the 17th International Congress of Parkinson’s disease and Movement Disorders, taking place from June 16 to 20, 2013, at the Sydney Convention and Exhibition Centre, Sydney, Australia.Ravi Anand, Newron’s CMO, stated: “Previous results have established that safinamide significantly improves motor symptoms, activities of daily living and motor fluctuations in PD patients. Responder rate analyses to be presented at the MDS conference will demonstrate that safinamide is associated with a highly clinically significant increase in responders based on an integrated measure of ON-time, OFF-time and motor function, compared to optimized standard of care in PD patients with motor fluctuations. These results will be part of the regulatory submission that Newron intends to file in the US and Europe in QIV/2013."* On April 22, 2013, Newron Pharmaceuticals and its partner Zambon have announced that they have presented results from Phase III studies with safinamide at the 9th International Congress on Mental Dysfunction & Other Non-Motor Features in Parkinson’s Disease and Related Disorders, on April 20, 2013.Statistically significant improvement in Quality of Life, as assessed by the Parkinson’s disease Quality of Life (PDQ-39) and/or the European Quality of Life (EuroQoL, EQ-5D) scales has been associated with short term (six months), and long term (eighteen to twenty four months) treatment with safinamide.In patients with early PD on a single dopamine agonist, safinamide 100mg/day was associated with significant improvement in PDQ-39 (p=0.03) and EQ-5D (p=0.005) after six months (MOTION study), while in studies 015/017, a statistically significant benefit of safinamide 50-100mg/day on EuroQoL (EQ-5D) was noted at 18 months of treatment (p=0.008), all compared to dopamine agonist monotherapy (placebo).Patients with moderate to severe PD with motor fluctuations stabilized on levodopa and other dopaminergic treatments (standard of care) experienced statistically significant improvement in PDQ-39 after six (p=0.036) and twenty four months (p=0.019) of treatment with 100mg/day of safinamide (study 016/018), compared to standard of care (placebo). In the SETTLE study, safinamide at a dose of 50-100 mg/day was associated with a statistically significant improvement in PDQ-39 (p=0.006) and EQ-5D (p<0.001) at six months, compared to standard of care (placebo).Safinamide filing for regulatory approval as add-on in early and mid-to late PD patients in EU and US is now expected in Q4/2013.
Newron and Zambon have concluded a strategic collaboration and license agreement for safinamide last year.
