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

Study Overview
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Brief Summary
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Parkinson's Disease is a major neurodegenerative disorder in which there is a progressive loss of dopamine-containing 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. Safinamide is an inhibitor of MAO-B. This is a phase III trial to evaluate the efficacy and safety of safinamide (50 and 100 mg p.o. q.a.m.) compared to placebo as add-on therapy to a stable dose to levodopa in subjects with advance idiopathic Parkinson's Disease. The principal efficacy measure is the increase in mean daily on time during the 18-hr diary recording period.

Official Title
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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

Conditions
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Idiopathic Parkinson's Disease

Intervention / Treatment
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* Drug: Safinimide 50-100 mg/day
* Drug: Matching Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female between the ages of 30 to 80 years with diagnosis of idiopathic Parkinson's Disease of more than 5 years duration, with a Hoehn and Yahr stage of I-IV during an off phase. Be levodopa-responsive and have been receiving treatment with a stable dose of levodopa for at least 4 weeks. Have motor fluctuations, with >1.5 hours off time during the day. Be able to maintain an accurate and complete diary (18-hour) Exclusion Criteria: Patients with medical conditions and/or taking concomitant medications that would have put them at risk, interfered with the study evaluations, or made them unable to complete the requirements of the study;. Be in a late stage of Parkinson's Disease, and experiencing severe, disabling peak-dose or biphasic dyskinesia and/or unpredictable or widely swinging fluctuations in their symptoms. Current diagnosis of substance abuse or history of alcohol or drug abuse in the past 3 months. Have received treatment with safinamide previously. History of, or current depression psychosis (e.g. schizophrenia or psychotic depression) Evidence of dementia or cognitive dysfunction. History of allergic response to anticonvulsants, levodopa, or other anti-Parkinsonian agents. Hypersensitivity or contraindications to MAO-B inhibitors. Ophthalmologic history including any of the following conditions: albino subjects, family history of hereditary retinal disease, progressive and/or severe diminution of visual acuity (i.e., 20/70), retinitis pigmentosa, retinal pigmentation due to any cause, any active retinopathy or ocular inflammation (uveitis), or diabetic retinopathy.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>1 active (50 - 100 mg/day) | Drug: Safinimide 50-100 mg/day<br>* Safinamide, (S)-(+)-2-[4-(3-fluorobenzyloxy) benzylamino] propanamide methanesulfonate, is an a-aminoamide derivative<br>|
| Placebo Comparator: 2<br> | Drug: Matching Placebo<br>* Matching Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the change from baseline to W24 in daily on time (on time without dyskinesia plus on time with minor dyskinesia) |  | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the changes from baseline to W24 in Activities of Daily Living, cognition, dyskinesias, change in global clinical status, motor symptoms, motor fluctuations, change in levopoda dose and Health Related Quality of life |  | 24 weeks |