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

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).

Time frame: Up to 28 Weeks including safety follow-up visit.

Population: Safety evaluation was based on Safety Set which included all 66 patients enrolled in the study.

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.

Time frame: Up to 28 Weeks including safety follow-up visit.

Population: Planned patient enrollment numbers were not achieved as this study and the tozadenant development program were terminated early, based on an unexpected emerging safety signal. No patient completed the 52 Week study treatment period prior to Sponsor termination of the study. .

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).

Time frame: Up to 28 Weeks including safety follow-up visit.

Population: Planned patient enrollment numbers were not achieved as this study and the tozadenant development program were terminated early, based on an unexpected emerging safety signal. No patient completed the 52 Week study treatment period prior to Sponsor termination of the study.

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.

Time frame: Up to 28 Weeks including safety follow-up visit.

Population: Planned patient enrollment numbers were not achieved as this study and the tozadenant development program were terminated early, based on an unexpected emerging safety signal. No patient completed the 52 Week study treatment period prior to Sponsor termination of the study.