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

Primary Purpose

Idiopathic Parkinson's Disease

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
tozadenant
placebo
Sponsored by
Biotie Therapies Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Idiopathic Parkinson's Disease focused on measuring Motor fluctuations, Off time, On time, Dyskinesia

Eligibility Criteria

30 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

Tozadenant 60 mg BID

Tozadenant 120 mg BID

Placebo BID

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Change From Baseline to Week 24 in the Number of Hours Per Day Spent in OFF Time
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

Change in Good ON Time From Baseline to Week 24
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
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
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.

Full Information

First Posted
May 21, 2015
Last Updated
March 25, 2019
Sponsor
Biotie Therapies Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02453386
Brief Title
Safety and Efficacy Study of Tozadenant to Treat End of Dose Wearing Off in Parkinson's Patients
Acronym
TOZ-PD
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)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2019
Overall Recruitment Status
Terminated
Why Stopped
New Safety Information
Study Start Date
July 2015 (Actual)
Primary Completion Date
January 12, 2018 (Actual)
Study Completion Date
January 12, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biotie Therapies Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Idiopathic Parkinson's Disease
Keywords
Motor fluctuations, Off time, On time, Dyskinesia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
449 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Tozadenant 60 mg BID
Arm Type
Experimental
Arm Description
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.
Arm Title
Tozadenant 120 mg BID
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo BID
Arm Type
Placebo Comparator
Arm Description
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 Type
Drug
Intervention Name(s)
tozadenant
Other Intervention Name(s)
SYN115
Intervention Type
Drug
Intervention Name(s)
placebo
Other Intervention Name(s)
tozadenant placebo
Primary Outcome Measure Information:
Title
Change From Baseline to Week 24 in the Number of Hours Per Day Spent in OFF Time
Description
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.
Time Frame
Baseline to 24 Weeks
Secondary Outcome Measure Information:
Title
Change in Good ON Time From Baseline to Week 24
Description
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.
Time Frame
Baseline to 24 Weeks
Title
Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Activities of Daily Living (ADL) Subscale + Part III Motor Function
Description
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.
Time Frame
Baseline to Week 24
Title
Change From Baseline to Week 24 in the ON State in Unified Parkinson's Disease Rating Scale (UPDRS) Part IIl
Description
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.
Time Frame
Baseline to Week 24
Other Pre-specified Outcome Measures:
Title
Global Assessments of Improvement: Clinical Global Impression of Improvement (CGI-I) Week 24
Description
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.
Time Frame
At Week 24
Title
Patient Global Impression of Improvement (PGI-I) Week 24
Description
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.
Time Frame
At Week 24

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 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
Biotie Inc.
Official's Role
Study Director
Facility Information:
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35005
Country
United States
City
Sun City
State/Province
Arizona
ZIP/Postal Code
85351
Country
United States
City
Loma Linda
State/Province
California
ZIP/Postal Code
92318
Country
United States
City
Los Angeles
State/Province
California
ZIP/Postal Code
90001
Country
United States
City
Oxnard
State/Province
California
ZIP/Postal Code
93030
Country
United States
City
Reseda
State/Province
California
ZIP/Postal Code
91335
Country
United States
City
Sacramento
State/Province
California
ZIP/Postal Code
914203
Country
United States
City
Sunnyvale
State/Province
California
ZIP/Postal Code
94043
Country
United States
City
Englewood
State/Province
Colorado
ZIP/Postal Code
80110
Country
United States
City
Vernon
State/Province
Connecticut
ZIP/Postal Code
06029
Country
United States
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33428
Country
United States
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32601
Country
United States
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32034
Country
United States
City
Tampa
State/Province
Florida
ZIP/Postal Code
33601
Country
United States
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30301
Country
United States
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30805
Country
United States
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60007
Country
United States
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66012
Country
United States
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40502
Country
United States
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02101
Country
United States
City
East Lansing
State/Province
Michigan
ZIP/Postal Code
48808
Country
United States
City
Farmington Hills
State/Province
Michigan
ZIP/Postal Code
48167
Country
United States
City
West Bloomfield
State/Province
Michigan
ZIP/Postal Code
48302
Country
United States
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63101
Country
United States
City
Albany
State/Province
New York
ZIP/Postal Code
12084
Country
United States
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
City
Rochester
State/Province
New York
ZIP/Postal Code
14602
Country
United States
City
Asheville
State/Province
North Carolina
ZIP/Postal Code
28715
Country
United States
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27517
Country
United States
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
41073
Country
United States
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44101
Country
United States
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43460
Country
United States
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74008
Country
United States
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19019
Country
United States
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37011
Country
United States
City
Houston
State/Province
Texas
ZIP/Postal Code
77001
Country
United States
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05401
Country
United States
City
Roanoke
State/Province
Virginia
ZIP/Postal Code
24001
Country
United States
City
Kirkland
State/Province
Washington
ZIP/Postal Code
98033
Country
United States
City
Innsbruck
Country
Austria
City
Vienna
Country
Austria
City
Edmonton
State/Province
Alberta
Country
Canada
City
Ottawa
State/Province
Ontario
Country
Canada
City
Toronto
State/Province
Ontario
Country
Canada
City
Brno
Country
Czechia
City
Chocen
Country
Czechia
City
Pardubice
Country
Czechia
City
Prague
Country
Czechia
City
Rychnov nad Kneznou
Country
Czechia
City
Beelitz-Heilstätten
Country
Germany
City
Berlin
Country
Germany
City
Dresden
Country
Germany
City
Haag in Oberbayern
Country
Germany
City
Marburg
Country
Germany
City
Ulm
Country
Germany
City
Arcugnano
Country
Italy
City
Cassino
Country
Italy
City
Chieti
Country
Italy
City
Grosseto
Country
Italy
City
Pavia
Country
Italy
City
Pisa
Country
Italy
City
Rome
Country
Italy
City
Salerno
Country
Italy
City
Venice
Country
Italy
City
Manresa
State/Province
Barcelona
Country
Spain
City
Sant Cugat del Valles
State/Province
Barcelona
Country
Spain
City
Terrassa
State/Province
Barcelona
Country
Spain
City
San Sebastian
State/Province
Guipuzcoa
Country
Spain
City
Barcelona
Country
Spain
City
Madrid
Country
Spain

12. IPD Sharing Statement

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Safety and Efficacy Study of Tozadenant to Treat End of Dose Wearing Off in Parkinson's Patients

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