Study to Evaluate SYN115 in Parkinson's Disease

Study Overview
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Brief Summary
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This is an exploratory study to evaluate if SYN115 has an effect on Parkinson's disease as measured by clinical symptoms and brain images using magnetic resonance imaging (MRI) when a function test is administered.

Detailed Description
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This is a randomized, double-blind, placebo-controlled, two-way crossover study in which each patient will act as their own control. Each patient enrolled will receive both SYN115 (20 mg or 60 mg) and placebo separated by a minimum of one week washout between periods. An adaptive design will be used to determine if SYN115 elicits effects relevant to PD in the fewest number of patients by performing interim analyses in successive cohorts of patients receiving 60 or 20 mg.

Official Title
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A Randomized, Double-blind, Placebo Controlled, Two-way Cross-over Study to Explore the Effects of 7 Days of Dosing With SYN115 20 mg p.o. BID or 60 mg p.o. BID on Clinical and fMRI Response to Intravenous Levodopa in Patients With Mild to Moderate Parkinson's Disease

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: Placebo
* Drug: Tozadenant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Parkinson's disease Hoen and Yahr stage 1-3 On stable dose of anti-parkinsons treatment for 30 days prior to screening Age 40 to 75 years Sign an IRB approved informed consent Men and women agree to use adequate birth control ECG measurements are within normal limits Able to understand study requirements Exclusion Criteria: Secondary Parkinson's (drug induced or post stroke) Received treatment with other investigational drug 30 days prior to study entry Using disallowed medications Significant neurological illness other than Parkinson's IQ less than 70 on IQ test MMSE score < or = 23 History of psychosis or on anti-psychotic medication Current serious medical illness History of substance abuse History of head injury with loss of consciousness History of brain surgery Contraindications to MRI like claustrophobia, metal implants or other implantable devices Abnormal liver function tests and/or hepatitis or cholangitis Gilberts disease Pregnant or nursing Known hypersensitivity to SYN115

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Active medication Tozadenant 20 mg oral capsules with a daily dosage of either 20 mg BID or 60 mg BID | Drug: Tozadenant<br>* 20 mg oral capsules with a daily dosage of either 20 mg BID or 60 mg BID<br>* Other names: SYN115;|
| Placebo Comparator: 2<br>Crossover from arm 1 to arm 2 with one week washout. One of the arms is placebo control | Drug: Placebo<br>* Placebo oral capsules Placebo for 7 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| This is an exploratory study to evaluate effects of SYN115 in patients with PD, as determined by clinical and fMRI evaluation. The results of this initial study will help determine the range to be used in subsequent studies. |  | Before treatment and at the end of each treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pittsburgh side effect scale |  | Before, after the first dose and end of each treatment period | 
| VAS for overall well being, dizziness/light-headedness, nausea/vomiting, mood anxiety |  | Before, after the first dose and end of each treatment period | 
| Measurement of motor symptoms of Parkinson's disease and tapping speed |  | Before, after the first dose and end of each treatment period |