Back to resultsSafety and Tolerability of Tozadenant as Adjunctive Therapy in Levodopa-Treated Patients With Parkinson's Disease.
Primary Purpose
Idiopathic Parkinson Disease
Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Tozadenant
Sponsored by
About this trial
This is an interventional treatment trial for Idiopathic Parkinson Disease focused on measuring Motor Fluctuations, Off time, On time, Dyskinesia
Eligibility Criteria
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
Sites / Locations
- Barrow Neurology Clinics, St. Joseph's Hospital and Medical Center, Dignity Health
- University of Arkansas for Medical Sciences
- Collaborative Neuroscience Network, LLC
- USC, Keck School of Medicine
- SC3 Research Group
- JEM Research Institute
- Aventura Neurologic Associates
- Parkinson's Disease and Movement Disorders Center of Boca Raton
- Neurology Associates, P.A.
- Neurology Associates of Ormond Beach
- Parkinson's Disease Treatment Center of SW Florida
- Infinity Clinical Research
- Hawaii Pacific Neuroscience
- Unity Point Health
- Unity Point Health
- University of Kansas Medical Center
- University of Kentucky, Department of Neurology
- Henry Ford West Bloomfield Hospital
- Struthers Parkinson's Center
- Struthers Parkinson's Center
- The Robert and John M. Bendheim Parkinson and Movement Disorders Center
- Asheville Neurology Specialists, PA
- Raleigh Neurology Associates
- Movement Disorders Clinic of Oklahoma
- Abington Neurological Associates
- Baylor College of Medicine
- University of Virginia, Department of Neurology
- Booth Gardner Parkinson's Care Center
- Premier Clinical Research
- University of Wisconsin-Madison
- University of Wisconsin - Madison
- Ottawa Hospital Research Institute
- The Walton Centre NHS Foundation Trust, Neuroscience Research Center
- Newcastle University Clinical Ageing Research Unit (CARU)
- The Queen Elizabeth University Hospital Department of Neurology
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Tozadenant
Arm Description
120 mg twice daily. At Week 2 or thereafter doses of 60 mg BID and 120 mg BID will be permitted.
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
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.
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).
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.
Full Information
NCT ID
NCT03051607
First Posted
February 9, 2017
Last Updated
April 9, 2019
Sponsor
Biotie Therapies Inc.
Collaborators
Acorda Therapeutics
1. Study Identification
Unique Protocol Identification Number
NCT03051607
Brief Title
Safety and Tolerability of Tozadenant as Adjunctive Therapy in Levodopa-Treated Patients With Parkinson's Disease.
Official Title
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"
Study Type
Interventional
2. Study Status
Record Verification Date
April 2019
Overall Recruitment Status
Terminated
Why Stopped
New Safety Information
Study Start Date
April 10, 2017 (Actual)
Primary Completion Date
January 16, 2018 (Actual)
Study Completion Date
January 16, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biotie Therapies Inc.
Collaborators
Acorda Therapeutics
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Idiopathic Parkinson Disease
Keywords
Motor Fluctuations, Off time, On time, Dyskinesia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
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)
Allocation
N/A
Enrollment
66 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tozadenant
Arm Type
Experimental
Arm Description
120 mg twice daily. At Week 2 or thereafter doses of 60 mg BID and 120 mg BID will be permitted.
Intervention Type
Drug
Intervention Name(s)
Tozadenant
Other Intervention Name(s)
SYN115
Intervention Description
1 Year Open Label, 120 mg BID tozadenant, with dose modification to 60 mg BID tozadenant permitted.
Primary Outcome Measure Information:
Title
To Evaluate the Safety and Tolerability of Tozadenant in Levodopa-treated PD Patients Experiencing Motor Fluctuations.
Description
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.
Secondary Outcome Measure Information:
Title
To Evaluate the Effects of Tozadenant on the Occurrences of Daytime Drowsiness by Using the Epworth Sleepiness Scale.
Description
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.
Title
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.
Description
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.
Title
To Evaluate the Effects of Tozadenant on the Number of Participants With Occurrence of Impulsive Behavior - Modified Minnesota Impulse Disorder Interview (mMIDI)
Description
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.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christopher Kenney, MD
Organizational Affiliation
Acorda Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
Barrow Neurology Clinics, St. Joseph's Hospital and Medical Center, Dignity Health
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85013
Country
United States
Facility Name
University of Arkansas for Medical Sciences
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
77215
Country
United States
Facility Name
Collaborative Neuroscience Network, LLC
City
Long Beach
State/Province
California
ZIP/Postal Code
90802
Country
United States
Facility Name
USC, Keck School of Medicine
City
Los Angeles
State/Province
California
ZIP/Postal Code
90089
Country
United States
Facility Name
SC3 Research Group
City
Pasadena
State/Province
California
ZIP/Postal Code
91105
Country
United States
Facility Name
JEM Research Institute
City
Atlantis
State/Province
Florida
ZIP/Postal Code
33462
Country
United States
Facility Name
Aventura Neurologic Associates
City
Aventura
State/Province
Florida
ZIP/Postal Code
33180
Country
United States
Facility Name
Parkinson's Disease and Movement Disorders Center of Boca Raton
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33486
Country
United States
Facility Name
Neurology Associates, P.A.
City
Maitland
State/Province
Florida
ZIP/Postal Code
32751
Country
United States
Facility Name
Neurology Associates of Ormond Beach
City
Ormond Beach
State/Province
Florida
ZIP/Postal Code
32174
Country
United States
Facility Name
Parkinson's Disease Treatment Center of SW Florida
City
Port Charlotte
State/Province
Florida
ZIP/Postal Code
33980
Country
United States
Facility Name
Infinity Clinical Research
City
Sunrise
State/Province
Florida
ZIP/Postal Code
33513
Country
United States
Facility Name
Hawaii Pacific Neuroscience
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96817
Country
United States
Facility Name
Unity Point Health
City
Des Moines
State/Province
Iowa
ZIP/Postal Code
10034
Country
United States
Facility Name
Unity Point Health
City
Des Moines
State/Province
Iowa
ZIP/Postal Code
50312
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
University of Kentucky, Department of Neurology
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Facility Name
Henry Ford West Bloomfield Hospital
City
Bloomfield Hills
State/Province
Michigan
ZIP/Postal Code
48322
Country
United States
Facility Name
Struthers Parkinson's Center
City
Golden Valley
State/Province
Minnesota
ZIP/Postal Code
55416
Country
United States
Facility Name
Struthers Parkinson's Center
City
Golden Valley
State/Province
Minnesota
ZIP/Postal Code
55427
Country
United States
Facility Name
The Robert and John M. Bendheim Parkinson and Movement Disorders Center
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Asheville Neurology Specialists, PA
City
Asheville
State/Province
North Carolina
ZIP/Postal Code
28806
Country
United States
Facility Name
Raleigh Neurology Associates
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27607
Country
United States
Facility Name
Movement Disorders Clinic of Oklahoma
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74136
Country
United States
Facility Name
Abington Neurological Associates
City
Willow Grove
State/Province
Pennsylvania
ZIP/Postal Code
27607
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Virginia, Department of Neurology
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
98034
Country
United States
Facility Name
Booth Gardner Parkinson's Care Center
City
Kirkland
State/Province
Washington
ZIP/Postal Code
98034
Country
United States
Facility Name
Premier Clinical Research
City
Spokane
State/Province
Washington
ZIP/Postal Code
99202
Country
United States
Facility Name
University of Wisconsin-Madison
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53705
Country
United States
Facility Name
University of Wisconsin - Madison
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53706
Country
United States
Facility Name
Ottawa Hospital Research Institute
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1Y 4E9
Country
Canada
Facility Name
The Walton Centre NHS Foundation Trust, Neuroscience Research Center
City
Liverpool
State/Province
England
ZIP/Postal Code
L9 7U
Country
United Kingdom
Facility Name
Newcastle University Clinical Ageing Research Unit (CARU)
City
Newcastle upon Tyne
State/Province
England
ZIP/Postal Code
NE4 5PL
Country
United Kingdom
Facility Name
The Queen Elizabeth University Hospital Department of Neurology
City
Glasgow
State/Province
Scottland
ZIP/Postal Code
G51 4TF
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Safety and Tolerability of Tozadenant as Adjunctive Therapy in Levodopa-Treated Patients With Parkinson's Disease.
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