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Safety and Efficacy Study of Tozadenant to Treat End of Dose Wearing Off in Parkinson's Patients (TOZ-PD)

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: NCT02453386
Recruitment Status : Terminated (New Safety Information)
First Posted : May 25, 2015
Results First Posted : March 26, 2019
Last Update Posted : April 3, 2019
Sponsor:
Information provided by (Responsible Party):
Biotie Therapies Inc.

Tracking Information
First Submitted Date  ICMJE May 21, 2015
First Posted Date  ICMJE May 25, 2015
Results First Submitted Date  ICMJE January 31, 2019
Results First Posted Date  ICMJE March 26, 2019
Last Update Posted Date April 3, 2019
Actual Study Start Date  ICMJE July 2015
Actual Primary Completion Date January 12, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 4, 2019)
Change From Baseline to Week 24 in the Number of Hours Per Day Spent in OFF Time [ Time Frame: Baseline to 24 Weeks ]
Awake time in OFF state (hr) is the average of maximum of 3 days diary. The primary efficacy endpoint was the change from baseline to Week 24 in OFF time, where OFF time in the Hauser Parkinson's Disease Home Diary (PD) was averaged over 3 days prior to the study visit. During Screening and through Part A of the study, the Hauser Parkinson's Disease Home Diary (PD) was completed on specified days directly preceding the scheduled study visits/assessments. Motor activity was recorded as OFF, ON (mobility improved), or asleep time. Patients were asked to record ON time according to dyskinesia categories "without dyskinesia", "with non troublesome dyskinesia" or "with troublesome dyskinesia". Patients (and/or caregivers) were trained to complete the PD diary to record their status at half hourly intervals as OFF, ON without dyskinesia, ON with non troublesome dyskinesia, ON with troublesome dyskinesia, or asleep.
Original Primary Outcome Measures  ICMJE
 (submitted: May 21, 2015)
Number of hours per day spent in the OFF state [ Time Frame: Baseline to Week 24 ]
Assessed by patient-completed PD diaries and averaged over 3 consecutive days
Change History Complete list of historical versions of study NCT02453386 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 4, 2019)
  • Change in Good ON Time From Baseline to Week 24 [ Time Frame: Baseline to 24 Weeks ]
    The first key secondary efficacy endpoint was the change from baseline to Week 24 in good ON which was defined as ON without dyskinesia or ON with non-troublesome dyskinesia. Awake Time in Good ON State (hr) is the average of a maximum of 3 days diary. Patients were asked to record ON time according to dyskinesia categories "without dyskinesia", "with non troublesome dyskinesia" or "with troublesome dyskinesia" . Patients (and/or caregivers) were trained to complete the PD diary to record their status at half hourly intervals as OFF, ON without dyskinesia, ON with non troublesome dyskinesia, ON with troublesome dyskinesia, or asleep. For patients with missing baseline or baseline was measured post-dose, screening was used as baseline in the calculation of change from baseline.
  • Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Activities of Daily Living (ADL) Subscale + Part III Motor Function [ Time Frame: Baseline to Week 24 ]
    The Unified Parkinson's Disease Rating Scale (UPDRS) is a scale to monitor Parkinson's Disease related disability and impairment. The scale itself has 4 components are titled; (1) nonmotor experiences of daily living (13 items), (2) motor experiences of daily living (13 items), (3) motor examination (18 items), and (4) motor complications (six items). Each subscale now has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. In this outcome measure we are evaluating Part II and Part III. Part II: self-evaluation of the activities of daily life (ADLs) including speech, swallowing, handwriting, dressing, hygiene, falling, salivating, turning in bed, walking, and cutting food Part III: clinician-scored monitored motor evaluation Range of score is 0 - 160: 0 meaning less impact and Higher score indicates greater impact of PD symptoms.
  • Change From Baseline to Week 24 in the ON State in Unified Parkinson's Disease Rating Scale (UPDRS) Part IIl [ Time Frame: Baseline to Week 24 ]
    Change from Baseline to Week 24 in the Unified Parkinson's Disease Rating Scale (UPDRS) Parts III Motor Function (motor subscale) total scores. Each subscale has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Range of score is 0 - 108. Higher scores indicate greater impact of PD symptoms. Unified Parkinson's Disease Rating Scale (UPDRS) in the ON state was measured at a time representative of the ON state in that patient, not in "best" ON. Unified Parkinson's Disease Rating Scale Part III in OFF was not evaluated.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 21, 2015)
  • Number of hours per day spent in ON time without dyskinesia and ON time with non troublesome dyskinesia. [ Time Frame: Baseline to Week 24 ]
    Assessed by patient-completed PD diaries and averaged over 3 consecutive days
  • UPDRS Part II + Part III [ Time Frame: Baseline to Week 24 ]
    United Parkinson's Disease Rating Scale Parts II (ADL subscale) + III (motor subscale) total scores.
Current Other Pre-specified Outcome Measures
 (submitted: March 4, 2019)
  • Global Assessments of Improvement: Clinical Global Impression of Improvement (CGI-I) Week 24 [ Time Frame: At Week 24 ]
    For the Clinical Global Impression of Improvement (CGI-I), the investigator or rater is asked to rate the patient's total improvement, whether or not in his or her judgment it is due entirely to drug treatment, based on a 1-7 point weighted scale ranging from "very much improved" (1) to "very much worse" (7). A zero score is assigned if the score is not assessed. Scale: 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, 7 = Very much worse. Tables show Treatment vs Placebo.
  • Patient Global Impression of Improvement (PGI-I) Week 24 [ Time Frame: At Week 24 ]
    For the Patient Global Impression of Improvement (PG-I), the patient is asked to rate the total improvement of their Parkinson's Disease, whether or not in the patient's judgment it is due entirely to drug treatment, based on a 1-7 point weighted scale. "very much improved" (1) to "very much worse" (7). A zero score is assigned if the score is not assessed. Scale: 1 = Normal, not at all ill, 2 = Borderline ill, 3 = Mildly ill, 4 = Moderately ill, 5 = Markedly ill, 6 = Severly ill, 7 = Among the most extremely ill. Tables show Treatment vs Placebo.
Original Other Pre-specified Outcome Measures
 (submitted: May 21, 2015)
  • CGI-I [ Time Frame: Week 24 ]
    Clinical Global Impression - Improvement
  • PGI-I [ Time Frame: Week 24 ]
    Patient Global Impression - Improvement
  • UPDRS Part III [ Time Frame: Baseline to Week 24 ]
    United Parkinson's Disease Rating ScalePart III (motor subscale) total score
  • CGI-S [ Time Frame: Baseline to Week 24 ]
    Clinical Global Impressions - severity of illness
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy Study of Tozadenant to Treat End of Dose Wearing Off in Parkinson's Patients
Official Title  ICMJE A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Determine the Efficacy and Safety of Tozadenant as Adjunctive Therapy in Levodopa-Treated Patients With Parkinson's Disease Experiencing End of Dose "Wearing-Off" (TOZ-PD)
Brief Summary Phase 3, international, multicenter, randomized, double-blind, placebo-controlled, parallel-group, 3-arm safety and efficacy study (Part A) with an open-label phase (Part B).
Detailed Description

During Part A, each patient will participate for up to 30 weeks, which includes a Screening Period of 1 to ≤ 6 weeks, followed by a Baseline Visit and 24 weeks of double-blind treatment:

  • Screening Period: 1 - 6 weeks.
  • Double-Blind Treatment Period: 24 weeks.

After completion of Part A, patients will continue in Part B for an additional 56 weeks:

  • Open-Label Treatment Period: 52 weeks.
  • Post-Treatment Safety Follow Up: 4 weeks.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Idiopathic Parkinson's Disease
Intervention  ICMJE
  • Drug: tozadenant
    Other Name: SYN115
  • Drug: placebo
    Other Name: tozadenant placebo
Study Arms  ICMJE
  • Experimental: Tozadenant 60 mg BID

    During Part A, patients took two (2) tablets, one 60 mg tozadenant and one placebo, by mouth BID for a total of four (4) tablets per day.

    Upon completion of Part A, all patients will begin dosing with open label tozadenant in Part B.

    Intervention: Drug: tozadenant
  • Experimental: Tozadenant 120 mg BID

    During Part A, patients took two (2) tablets of 60 mg tozadenant, by mouth BID for a total of four (4) tablets per day.

    Upon completion of Part A, all patients will begin dosing with open label tozadenant in Part B.

    Intervention: Drug: tozadenant
  • Placebo Comparator: Placebo BID

    During Part A, patients took two (2) tablets of placebo, by mouth BID for a total of four (4) tablets per day.

    Upon completion of Part A, all patients will begin dosing with open label tozadenant in Part B.

    Intervention: Drug: placebo
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 22, 2017)
449
Original Estimated Enrollment  ICMJE
 (submitted: May 21, 2015)
450
Actual Study Completion Date  ICMJE January 12, 2018
Actual Primary Completion Date January 12, 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
  • 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 Austria,   Canada,   Czechia,   Germany,   Italy,   Spain,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT02453386
Other Study ID Numbers  ICMJE TOZ-CL05
2014-005630-60 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Biotie Therapies Inc.
Study Sponsor  ICMJE Biotie Therapies Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Christopher Kenney, MD Biotie Inc.
PRS Account Biotie Therapies Inc.
Verification Date March 2019

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