Safety and Efficacy Study of SYN115 in Parkinson's Patients Using Levodopa to Treat End of Dose Wearing Off

Study Overview
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Brief Summary
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The purpose of this research study is to test the effect of SYN115 compared to placebo (a sugar pill that looks like SYN115 but does not include active drug) on movement during the on and off states as well as other symptoms that some patients with Parkinson's disease experience. This study will also look at whether or not patients with Parkinson's disease experience side-effects with SYN115.

Official Title
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A Double-blind, Randomized, Placebo-controlled Study of the Safety and Efficacy of SYN115 as Adjunctive Therapy in Levodopa-treated Parkinson's Subjects With End of Dose Wearing Off

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: Tozadenant (SYN115) 60 mg BID
* Drug: Placebo
* Drug: Levodopa (L-dopa)
* Drug: Tozadenant (SYN115) 120 mg BID
* Drug: Tozadenant (SYN115) 180 mg BID
* Drug: Tozadenant (SYN115) 240 mg BID


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meet Parkinson's Disease (PD) diagnosis consistent with UK PD diagnostic criteria Meet Hoehn and Yahr PD stage Good response to levodopa Stable regimen of anti-parkinson medications Are able to complete a Parkinson's disease diary If of childbearing potential(male and female), use an acceptable method of birth control Able and willing to sign an IRB/IEC approved informed consent Able and willing to understand study requirements, follow study instructions, attend all visits and undergo all planned tests. Exclusion Criteria: Secondary or atypical Parkinson's Neurosurgical intervention for Parkinson's disease Treatment with apomorphine Treatment with anti-psychotic drugs Other abnormal findings on physical or neuro exam or history that in the opinion of the investigator would make subject unsuitable for the study or prejudice safety and efficacy evaluation MMSE less than 26 Subjects with untreated or uncontrolled current episode of major depression Receipt of any anti-psychotic drugs greater than 1 month in the past 5 years or any exposure in past year (except for quetiapine at doses <100mg per day) Women pregnant or lactating History of hepatitis, cholangitis Untreated or uncontrolled hypothyroidism or hyperthyroidism Drops in blood pressure requiring medication to maintain blood pressure Any clinically significant out of range laboratory evaluations Known sensitivity to the study medication or its components Suicide ideation or type 4 or type 5 on the Columbia suicide severity rating scale Finding of malignant melanoma on full body skin exam Impulse disorder conditions

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tozadenant (SYN115) 60 mg BID<br>Tozadenant tablets, white-coated, modified-oval tablets manufactured in 60 mg dosage strengths. | Drug: Tozadenant (SYN115) 60 mg BID<br>* Tozadenant tablets, white-coated, modified-oval tablets manufactured in 60 mg dosage strengths. Total daily doses include 60 mg BID.<br>Drug: Levodopa (L-dopa)<br>* One intravenous infusion of L-dopa to reach approximately 600 ng/ ml plasma concentration.<br>* Other names: L-dopa;|
| Experimental: Tozadenant (SYN115) 120 mg BID<br>Tozadenant tablets, white-coated, modified-oval tablets manufactured in 60 mg dosage strengths. | Drug: Levodopa (L-dopa)<br>* One intravenous infusion of L-dopa to reach approximately 600 ng/ ml plasma concentration.<br>* Other names: L-dopa;Drug: Tozadenant (SYN115) 120 mg BID<br>* Tozadenant tablets, white-coated, modified-oval tablets manufactured in 60 mg dosage strengths. Total daily doses include 120 mg BID.<br>|
| Experimental: Tozadenant (SYN115) 180 mg BID<br>Tozadenant tablets, white-coated, modified-oval tablets manufactured in 60 mg dosage strengths. | Drug: Levodopa (L-dopa)<br>* One intravenous infusion of L-dopa to reach approximately 600 ng/ ml plasma concentration.<br>* Other names: L-dopa;Drug: Tozadenant (SYN115) 180 mg BID<br>* Tozadenant tablets, white-coated, modified-oval tablets manufactured in 60 mg dosage strengths. Total daily doses include 180 mg BID.<br>|
| Experimental: Tozadenant (SYN115) 240 mg BID<br>Tozadenant tablets, white-coated, modified-oval tablets manufactured in 60 mg dosage strengths. | Drug: Levodopa (L-dopa)<br>* One intravenous infusion of L-dopa to reach approximately 600 ng/ ml plasma concentration.<br>* Other names: L-dopa;Drug: Tozadenant (SYN115) 240 mg BID<br>* Tozadenant tablets, white-coated, modified-oval tablets manufactured in 60 mg dosage strengths. Total daily doses include 240 mg BID.<br>|
| Placebo Comparator: Sugar Pill<br>White-coated, modified-oval placebo tablets. | Drug: Placebo<br>* White-coated, modified-oval placebo tablets.<br>Drug: Levodopa (L-dopa)<br>* One intravenous infusion of L-dopa to reach approximately 600 ng/ ml plasma concentration.<br>* Other names: L-dopa;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess efficacy of different doses of SYN115 for reducing the mean total hours of awake time per day spent in the off state |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the effect of SYN115 on dyskinesia |  | 12 weeks | 
| To assess the effect of SYN115 on UPDRS scores |  | 12 weeks | 
| To assess investigator and patient impressions of PD severity and change |  | 12 weeks | 
| To assess the effect of SYN115 on non motor symptoms of PD |  | 12 weeks | 
| To assess the safety and tolerability of SYN115 |  | 12 weeks | 
| To assess the effects of SYN115 on daytime drowsiness, impulsive behavior, development of melanoma and suicidal ideation |  | 12 weeks |