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

Phase 3

Terminated

Conditions: Idiopathic Parkinson Disease

Interventions: Drug: Tozadenant

Registration Number: NCT03051607

Lead Sponsor: Biotie Therapies Inc.

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

Detailed Description: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 66

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Tozadenant	Tozadenant	120 mg twice daily. At Week 2 or thereafter doses of 60 mg BID and 120 mg BID will be permitted.

Primary Outcome Measures

Name	Time	Method
To Evaluate the Safety and Tolerability of Tozadenant in Levodopa-treated PD Patients Experiencing Motor Fluctuations.	Up to 28 Weeks including safety follow-up visit.	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).

Secondary Outcome Measures

Name	Time	Method
To Evaluate the Effects of Tozadenant on the Number of Participants With Occurrence of Impulsive Behavior - Modified Minnesota Impulse Disorder Interview (mMIDI)	Up to 28 Weeks including safety follow-up visit.	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.
To Evaluate the Effects of Tozadenant on the Occurrences of Daytime Drowsiness by Using the Epworth Sleepiness Scale.	Up to 28 Weeks including safety follow-up visit.	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.
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.	Up to 28 Weeks including safety follow-up 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).

Trial Locations

Locations (33): Newcastle University Clinical Ageing Research Unit (CARU)
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Newcastle upon Tyne, England, United Kingdom
The Queen Elizabeth University Hospital Department of Neurology
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Glasgow, Scottland, United Kingdom
SC3 Research Group
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Pasadena, California, United States
Neurology Associates of Ormond Beach
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Ormond Beach, Florida, United States
Raleigh Neurology Associates
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Raleigh, North Carolina, United States
Asheville Neurology Specialists, PA
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Asheville, North Carolina, United States
Infinity Clinical Research
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Sunrise, Florida, United States
Struthers Parkinson's Center
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Golden Valley, Minnesota, United States
Collaborative Neuroscience Network, LLC
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Long Beach, California, United States
JEM Research Institute
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Atlantis, Florida, United States
Unity Point Health
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Des Moines, Iowa, United States
Parkinson's Disease and Movement Disorders Center of Boca Raton
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Boca Raton, Florida, United States
Neurology Associates, P.A.
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Maitland, Florida, United States
Henry Ford West Bloomfield Hospital
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Bloomfield Hills, Michigan, United States
Parkinson's Disease Treatment Center of SW Florida
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Port Charlotte, Florida, United States
Hawaii Pacific Neuroscience
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Honolulu, Hawaii, United States
The Robert and John M. Bendheim Parkinson and Movement Disorders Center
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New York, New York, United States
Premier Clinical Research
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Spokane, Washington, United States
University of Wisconsin-Madison
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Madison, Wisconsin, United States
Ottawa Hospital Research Institute
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Ottawa, Ontario, Canada
The Walton Centre NHS Foundation Trust, Neuroscience Research Center
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Liverpool, England, United Kingdom
Aventura Neurologic Associates
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Aventura, Florida, United States
Movement Disorders Clinic of Oklahoma
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Tulsa, Oklahoma, United States
University of Virginia, Department of Neurology
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Charlottesville, Virginia, United States
Barrow Neurology Clinics, St. Joseph's Hospital and Medical Center, Dignity Health
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Phoenix, Arizona, United States
USC, Keck School of Medicine
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Los Angeles, California, United States
Baylor College of Medicine
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Houston, Texas, United States
University of Arkansas for Medical Sciences
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Little Rock, Arkansas, United States
University of Kentucky, Department of Neurology
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Lexington, Kentucky, United States
Abington Neurological Associates
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Willow Grove, Pennsylvania, United States
Booth Gardner Parkinson's Care Center
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Kirkland, Washington, United States
University of Wisconsin - Madison
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Madison, Wisconsin, United States
University of Kansas Medical Center
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Kansas City, Kansas, United States