Safinamide in Idiopathic Parkinson's Disease (IPD) With Motor Fluctuations, as Add-on to Levodopa (SETTLE)

This study is not yet open for participant recruitment.

Verified by EMD Serono, February 2008

Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Parallel Assignment, Safety/Efficacy Study
Official Title: A Phase III, Double-Blind, Placebo-Controlled, Randomised Trial to Determine the Efficacy and Safety of a Dose Range of 50 to 100 mg/Day of Safinamide, as Add-on Therapy, in Subjects With Idiopathic Parkinson's Disease With Motor Fluctuations, Treated With a Stable Dose of Levodopa and Who May be Receiving Concomitant Treatment With Stable Doses of a Dopamine Agonist, an Anticholinergic and/or Amantadine


Purpose

Parkinson's Disease is a major neurodegenerative disorder in which there is a progressive loss of nigrostriatal dopaminergic neurons. The understanding that PD is a syndrome of dopamine (DA) deficiency led to the introduction in the clinical practice of L-dopa, a precursor of DA that crosses the blood brain barrier, and also to the use of selective inhibitors of MAO-B, the major DA metabolising enzyme in man. Recently it has been suggested that they might also slow disease progression by reducing oxidative damage.

Glutamate also plays a role in dopaminergic transmission and may contribute to the pathogenesis of motor fluctuations and neuronal cell loss.

This is a Phase III trial dose range of 50 to 100 mg/day of safinamide versus placebo as add-on therapy in subjects with early idiopathic Parkinson's Disease with motor fluctuations treated with a stable dose of levodopa and who may be receiving concomitant treatment with stable doses of a dopamine agonist, an anticholinergic and/or amantadine.

The objectives of this trial are to evaluate the efficacy and safety. The principal efficacy measure is the increase in mean daily "on" time during the 18-hr diary recording period.

Watch here for information about recruitment:
Clinical Trials.gov
PDTrials.org

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Phase III data on Safinamide in Parkinson's disease
Medical Studies/Trials
Published: Sunday, 6-May-2007
http://www.news-medical.net/?id=24692

Merck Serono S.A. has announced that Phase III data on safinamide, a new agent in Phase III development for the treatment of Parkinson's disease symptoms, were presented by Professor Fabrizio Stocchi at the American Academy of Neurology 59th Annual Meeting in Boston, Massachusetts, USA.

These data are from a 6-month (24 weeks), randomized, double blind, placebo-controlled, international trial.

"These data are promising for patients with Parkinson's disease," said Fabrizio Stocchi, Professor of Neurology and Honorary Consultant at the IRCCS San Raffaele Rome, University La Sapienza, and principal investigator of the study. "The data not only show the benefit of safinamide on motor symptoms and activities of daily living, but also indicate an effect on cognitive performance, which may represent a major advantage for the patient."

The data demonstrated that the addition of safinamide to a stable dose of a single dopamine agonist in patients with early stage Parkinson's disease resulted in a statistically significant improvement in motor symptoms, as measured by the Unified Parkinson's Disease Rating Scale(1) (UPDRS) Part III Motor Score (primary endpoint). After 24 weeks of treatment with safinamide at the dose of 50 to 100 mg once daily, the UPDRS Part III Motor Score was significantly improved over the effect of dopamine agonist monotherapy (difference between end of study and baseline of minus 6.0 plus or minus 7.2 in the safinamide-treated group versus minus 3.6 plus or minus 7.1 in the placebo group; p=0.0419; 95% CI=[-3.7;-0.1]).

In addition, treatment with safinamide at the dose of 50 to 100 mg once daily over a 24-week period resulted in a significant improvement of UPDRS Part II Activities of Daily Living Score, compared with dopamine agonist monotherapy (difference between end of study and baseline of minus 2.2 plus or minus 3.8 in the safinamide-treated group versus minus 1.2 plus or minus 3.5 in the placebo group; p=0.0248; 95% CI=[-1.8;-0.1]).

Safinamide was also studied for effects on cognition. Compared with patients on dopamine agonist monotherapy, the addition of safinamide was associated with an improvement in cognitive function as shown by an improvement in tests assessing spatial working memory, strategic target detection and auditory number sequencing.

The side effects observed in the safinamide group were similar to those observed in the placebo group.

The trial was conducted in Europe, South America and Asia. A total of 270 early stage Parkinson's disease patients (less than 5 years of disease) treated with a stable dose of a single dopamine agonist for at least 4 weeks were randomized to one of the three arms of the study to receive either safinamide at a dose of 50 to 100 mg once daily (90 patients), or safinamide at a dose of 150 to 200 mg once daily (90 patients) or matching placebo tablets (90 patients), as an add-on treatment to dopamine agonist therapy.

The higher safinamide dose-range of 150 to 200 mg per day did not offer any incremental advantage over safinamide 50 to 100 mg per day dose-range based on UPDRS scoring.

A one-year (52-week) extension phase of this study is ongoing. A second Phase III pivotal study of safinamide, in patients with mid-to-late stage Parkinson's disease with motor fluctuations treated with a stable dose of levodopa, was initiated in November 2006.

Merck Serono has exclusive worldwide rights to develop, manufacture and commercialize safinamide in Parkinson's disease, Alzheimer's disease, other cognitive disorders and restless leg syndrome, as per the agreement signed with Newron in October 2006.

(1) The UPDRS is one of the most widely used rating scales used to follow the course of Parkinson's disease.

It is made up of 42 items, scored from 0 to 4, to establish individual patients' mental status, activities of daily living, motor function and complications of therapy.

These are evaluated by interview and clinical observation. Clinicians and researchers alike use the UPDRS and the motor section in particular to follow the progression of a person's Parkinson's disease.

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