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

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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.

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).

Condition or disease Intervention/treatment Phase
Idiopathic Parkinson's Disease Drug: tozadenant Drug: placebo Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 449 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : July 2015
Actual Primary Completion Date : January 12, 2018
Actual Study Completion Date : January 12, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.

Drug: tozadenant
Other Name: SYN115

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.

Drug: tozadenant
Other Name: SYN115

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.

Drug: placebo
Other Name: tozadenant placebo




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.


  2. 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.


  3. 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.


Other Outcome Measures:
  1. 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.

  2. 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.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02453386


  Show 71 Study Locations
Sponsors and Collaborators
Biotie Therapies Inc.
Investigators
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Study Director: Christopher Kenney, MD Biotie Inc.
  Study Documents (Full-Text)

Documents provided by Biotie Therapies Inc.:
Study Protocol  [PDF] October 13, 2017
Statistical Analysis Plan  [PDF] May 19, 2015


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Responsible Party: Biotie Therapies Inc.
ClinicalTrials.gov Identifier: NCT02453386     History of Changes
Other Study ID Numbers: TOZ-CL05
2014-005630-60 ( EudraCT Number )
First Posted: May 25, 2015    Key Record Dates
Results First Posted: March 26, 2019
Last Update Posted: April 3, 2019
Last Verified: March 2019
Keywords provided by Biotie Therapies Inc.:
Motor fluctuations
Off time
On time
Dyskinesia
Additional relevant MeSH terms:
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Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases