Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03051607
Recruitment Status : Terminated (New Safety Information)
First Posted : February 13, 2017
Results First Posted : May 3, 2019
Last Update Posted : May 3, 2019
Sponsor:
Collaborator:
Acorda Therapeutics
Information provided by (Responsible Party):
Biotie Therapies Inc.

Tracking Information
First Submitted Date  ICMJE February 9, 2017
First Posted Date  ICMJE February 13, 2017
Results First Submitted Date  ICMJE January 14, 2019
Results First Posted Date  ICMJE May 3, 2019
Last Update Posted Date May 3, 2019
Actual Study Start Date  ICMJE April 10, 2017
Actual Primary Completion Date January 16, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 9, 2019)
To Evaluate the Safety and Tolerability of Tozadenant in Levodopa-treated PD Patients Experiencing Motor Fluctuations. [ Time Frame: 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).
Original Primary Outcome Measures  ICMJE
 (submitted: February 9, 2017)
  • Treatment Emergent Adverse Events (TEAEs) [ Time Frame: 12 months ]
    To evaluate the safety and tolerability of tozadenant in levodopa-treated PD patients experiencing motor fluctuations, based on number subjects with TEAEs
  • Vital Signs [ Time Frame: 12 months ]
    To evaluate the safety and tolerability of tozadenant in levodopa-treated PD patients experiencing motor fluctuations, based on changes in blood pressure and heart rate during treatment, including changes in orthostatic response
  • Electrocardiograms (ECGs) [ Time Frame: 12 months ]
    To evaluate the safety and tolerability of tozadenant in levodopa-treated PD patients experiencing motor fluctuations, based on changes on ECG recordinds of the RR, PR, QRS, QT and QTcF intervals.
  • Clinical Laboratory Tests [ Time Frame: 12 months ]
    To evaluate the safety and tolerability of tozadenant in levodopa-treated PD patients experiencing motor fluctuations, based on changes in clinical chemistry, hematology and urine samples
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 9, 2019)
  • To Evaluate the Effects of Tozadenant on the Occurrences of Daytime Drowsiness by Using the Epworth Sleepiness Scale. [ Time Frame: 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. [ Time Frame: 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).
  • To Evaluate the Effects of Tozadenant on the Number of Participants With Occurrence of Impulsive Behavior - Modified Minnesota Impulse Disorder Interview (mMIDI) [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Tolerability of Tozadenant as Adjunctive Therapy in Levodopa-Treated Patients With Parkinson's Disease.
Official Title  ICMJE 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"
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention 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)
Primary Purpose: Treatment
Condition  ICMJE Idiopathic Parkinson Disease
Intervention  ICMJE Drug: Tozadenant
1 Year Open Label, 120 mg BID tozadenant, with dose modification to 60 mg BID tozadenant permitted.
Other Name: SYN115
Study Arms  ICMJE Experimental: Tozadenant
120 mg twice daily. At Week 2 or thereafter doses of 60 mg BID and 120 mg BID will be permitted.
Intervention: Drug: Tozadenant
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: December 13, 2017)
66
Original Estimated Enrollment  ICMJE
 (submitted: February 9, 2017)
450
Actual Study Completion Date  ICMJE January 16, 2018
Actual Primary Completion Date January 16, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 30 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03051607
Other Study ID Numbers  ICMJE TOZ-CL06
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Biotie Therapies Inc.
Study Sponsor  ICMJE Biotie Therapies Inc.
Collaborators  ICMJE Acorda Therapeutics
Investigators  ICMJE
Study Director: Christopher Kenney, MD Acorda Therapeutics
PRS Account Biotie Therapies Inc.
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP