Safety and Tolerability of Tozadenant as Adjunctive Therapy in Levodopa-Treated Patients With Parkinson's Disease.

Study Overview
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Brief Summary
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Phase 3, international, multicenter, open-label 12 month safety study.

Detailed Description
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Each patient will participate for up to 52 weeks, which includes a Screening Period, followed by a Baseline Visit and open-label treatment for 1 year with a safety Follow-up 4 weeks after the last treatment. Screening Period: up to 6 weeks. Open-Label Treatment Period: 52 weeks (1 year) Post-Treatment Safety Follow Up: 4 weeks.

Official Title
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A Multicenter, Open-Label Study to Evaluate the Safety and Tolerability of Tozadenant as Adjunctive Therapy in Levodopa-Treated Patients With Parkinson's Disease Experiencing End of Dose Wearing-Off

Conditions
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Idiopathic Parkinson Disease

Intervention / Treatment
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* Drug: Tozadenant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient understands study requirements and has given his/her written informed consent on an Institutional Review Board (IRB) or Independent Ethics Committee (IEC) approved consent form. Parkinson's disease diagnosis consistent with UK Parkinson's Disease Society Brain Bank Diagnostic criteria Minimum of 3 years since diagnosis. Meet Hoehn and Yahr PD stage Good response to levodopa Stable regimen of anti-PD medications Patients must have been taking a levodopa-containing anti-PD medication continuously for at least the previous 12 months Patient has documented a minimum amount of Off time. If of childbearing potential (male and female) must use an acceptable method of contraception Exclusion Criteria: Previous tozadenant study participation Current or recent participation in another study. Secondary or atypical parkinsonism Neurosurgical intervention for PD (except DBS if electrode placement has been performed over 12 months prior to screening) Patient is taking apomorphine, budipine, istradefylline, tolcapone, or DUOPA™/Duodopa® Treatment with excluded medications Untreated or uncontrolled hyperthyroidism or hypothyroidism Clinically significant out-of-range laboratory MMSE out of range Current episode of major depression (stable treatment for depression is permitted). Recent suicide attempt or suicidal ideation type 4 or type 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) Women lactating or pregnant Hypersensitivity to any components of tozadenant or excipients Abnormal findings on the physical or neurological examination, or medical history that would make the patient unsuitable for the study History of hepatitis or cholangitis

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
Intervention Model: Single Group Assignment
Interventional Model Description: Eligible patients will begin dosing with tozadenant at a dose of 120 mg twice daily. At Week 2 or thereafter, the investigator may adjust the patient's IMP dose as clinically indicated; doses of 60 mg BID and 120 mg BID will be permitted.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tozadenant<br>120 mg twice daily. At Week 2 or thereafter doses of 60 mg BID and 120 mg BID will be permitted. | Drug: Tozadenant<br>* 1 Year Open Label, 120 mg BID tozadenant, with dose modification to 60 mg BID tozadenant permitted.<br>* Other names: SYN115;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Evaluate the Safety and Tolerability of Tozadenant in Levodopa-treated PD Patients Experiencing Motor Fluctuations. | The primary objective of this study was to evaluate the safety and tolerability of tozadenant in levodopa-treated Parkinson's Disease (PD) patients experiencing motor fluctuations, based on assessment of treatment-emergent adverse events (TEAEs), vital signs, electrocardiograms (ECGs), and clinical laboratory tests. A total of 66 patients were enrolled in 27 study centers across 6 countries: USA, United Kingdom, Italy, Canada, Spain and Hungary, and were included in the Safety Set (SS). | Up to 28 Weeks including safety follow-up visit. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Evaluate the Effects of Tozadenant on the Occurrences of Daytime Drowsiness by Using the Epworth Sleepiness Scale. | The Epworth Sleepiness Scale (ESS) is a scale intended to measure daytime sleepiness that is measured by use of a short questionnaire. Minimum range is 0 - Maximum range is 24. A score within the range 0-9 is considered to be normal while a score within the range of 10-24 would indicate that medical help should be solicited. | Up to 28 Weeks including safety follow-up visit. | 
| To Evaluate the Effects of Tozadenant on the Number of Participants With Suicidal Ideation or Behavior Using the Columbia-Suicide Severity Scale (C-SSRS) Summarized by Visit. | The Columbia Suicide Severity Rating Scale (C-SSRS) is a standardized suicidality rating system. The interview measures presence of suicidality and consists of 4 categories: suicidal ideation, intensity of ideation, suicidal behavior, and actual/potential lethality. Suicidal Ideation - A series of 1 -5 questions with 5 types of ideation of increasing severity. Score of Yes = 1, No= 0. A positive answer to question 4 (active suicidal ideation with some intent to act) or 5 (active suicidal ideation with specific plan and intent) indicates that the individual has some intent to act on suicidal thoughts and will need further evaluation. Suicidal Behavior - Different types of suicidal behavior are scored (Yes=1, No=0) and identify the occurrence of actual, interrupted, or aborted attempts; preparatory behaviors; and suicide. The total number of each type of suicidal behavior show the density of suicide, (more behaviors represent a higher degree of risk). | Up to 28 Weeks including safety follow-up visit. | 
| To Evaluate the Effects of Tozadenant on the Number of Participants With Occurrence of Impulsive Behavior - Modified Minnesota Impulse Disorder Interview (mMIDI) | The Minnesota Impulsive Disorders Interview (MIDI) 8 is a global instrument that includes questions for compulsive gambling, buying, and sexual behavior (as well as other disorders not reported to occur in PD). The mMIDI consists of 5 modules: compulsive buying, compulsive gambling, compulsive eating, hypersexuality and punding. Positive Answer: Any answer other than no on any question is considered a yes/positive answer. Negative Module: A module is considered negative if the patient's answer to a gateway (initial) question is no or if a patient answers yes to a gateway question and no to all of the remaining answers after the gateway question in that module. Positive Module: A module is considered positive if a patient gives a positive answer (No = 0, rarely = 1, occasionally = 2, frequently = 3) to any question after the gateway (initial) question in one or more of the 5 modules. | Up to 28 Weeks including safety follow-up visit. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Off time, On time, Motor Fluctuations, Dyskinesia