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

Idiopathic Parkinson Disease Clinical Trial

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"

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03051607
• Other study ID #: TOZ-CL06
• Status: Terminated
• Phase: Phase 3
• Start date: April 10, 2017
• Est. completion date: January 16, 2018

Study information

• Verified date: April 2019
• Source: Biotie Therapies Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Terminated
• Enrollment: 66
• Est. completion date: January 16, 2018
• Est. primary completion date: January 16, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Idiopathic Parkinson Disease
• Parkinson Disease

Intervention

Drug:
• Tozadenant
1 Year Open Label, 120 mg BID tozadenant, with dose modification to 60 mg BID tozadenant permitted.

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Biotie Therapies Inc.	Acorda Therapeutics

Countries where clinical trial is conducted

United States,  Canada,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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.
Secondary	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.