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

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"

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

Study Overview

• Status: Terminated
• Conditions: Idiopathic Parkinson Disease
• Intervention / Treatment: Drug: Tozadenant

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.

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1Y 4E9
      • Ottawa Hospital Research Institute
• United Kingdom
  • England
    • Liverpool, England, United Kingdom, L9 7U
      • The Walton Centre NHS Foundation Trust, Neuroscience Research Center
    • Newcastle upon Tyne, England, United Kingdom, NE4 5PL
      • Newcastle University Clinical Ageing Research Unit (CARU)
  • Scottland
    • Glasgow, Scottland, United Kingdom, G51 4TF
      • The Queen Elizabeth University Hospital Department of Neurology
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Barrow Neurology Clinics, St. Joseph's Hospital and Medical Center, Dignity Health
  • Arkansas
    • Little Rock, Arkansas, United States, 77215
      • University of Arkansas for Medical Sciences
  • California
    • Long Beach, California, United States, 90802
      • Collaborative Neuroscience Network, LLC
    • Los Angeles, California, United States, 90089
      • USC, Keck School of Medicine
    • Pasadena, California, United States, 91105
      • SC3 Research Group
  • Florida
    • Atlantis, Florida, United States, 33462
      • Jem Research Institute
    • Aventura, Florida, United States, 33180
      • Aventura Neurologic Associates
    • Boca Raton, Florida, United States, 33486
      • Parkinson's Disease and Movement Disorders Center of Boca Raton
    • Maitland, Florida, United States, 32751
      • Neurology Associates, P.A.
    • Ormond Beach, Florida, United States, 32174
      • Neurology Associates of Ormond Beach
    • Port Charlotte, Florida, United States, 33980
      • Parkinson's Disease Treatment Center of SW Florida
    • Sunrise, Florida, United States, 33513
      • Infinity Clinical Research
  • Hawaii
    • Honolulu, Hawaii, United States, 96817
      • Hawaii Pacific Neuroscience
  • Iowa
    • Des Moines, Iowa, United States, 10034
      • Unity Point Health
    • Des Moines, Iowa, United States, 50312
      • Unity Point Health
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky, Department of Neurology
  • Michigan
    • Bloomfield Hills, Michigan, United States, 48322
      • Henry Ford West Bloomfield Hospital
  • Minnesota
    • Golden Valley, Minnesota, United States, 55427
      • Struthers Parkinson's Center
    • Golden Valley, Minnesota, United States, 55416
      • Struthers Parkinson's Center
  • New York
    • New York, New York, United States, 10029
      • The Robert and John M. Bendheim Parkinson and Movement Disorders Center
  • North Carolina
    • Asheville, North Carolina, United States, 28806
      • Asheville Neurology Specialists, PA
    • Raleigh, North Carolina, United States, 27607
      • Raleigh Neurology Associates
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Movement Disorders Clinic of Oklahoma
  • Pennsylvania
    • Willow Grove, Pennsylvania, United States, 27607
      • Abington Neurological Associates
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
  • Virginia
    • Charlottesville, Virginia, United States, 98034
      • University of Virginia, Department of Neurology
  • Washington
    • Kirkland, Washington, United States, 98034
      • Booth Gardner Parkinson's Care Center
    • Spokane, Washington, United States, 99202
      • Premier Clinical Research
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin-Madison
    • Madison, Wisconsin, United States, 53706
      • University of Wisconsin - Madison

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Biotie Therapies Inc.
• Collaborators: Acorda Therapeutics
• Investigators: Study Director: Christopher Kenney, MD, Acorda Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2017
• Primary Completion (Actual): January 16, 2018
• Study Completion (Actual): January 16, 2018

Study Registration Dates

• First Submitted: February 9, 2017
• First Submitted That Met QC Criteria: February 9, 2017
• First Posted (Actual): February 13, 2017

Study Record Updates

• Last Update Posted (Actual): May 3, 2019
• Last Update Submitted That Met QC Criteria: April 9, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Dyskinesia; Motor Fluctuations; Off time; On time
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: TOZ-CL06

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No