A Phase 3, Multicenter, Randomized, Double-Blind, Placebo- Controlled Study with an Open-Label Phase 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)

• Register: EUCTR
• Last refreshed on: 12 February 2018
• Main ID: EUCTR2014-005630-60-AT
• Date of registration: 04/12/2015
• Prospective Registration: Yes
• Primary sponsor: Biotie Therapies Inc.(a wholly owned subsidiary of Acorda Therapeutics Inc.)
• Public title: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo- Controlled Study with an Open-Label Phase 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)
• Scientific title: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo- Controlled Study with an Open-Label Phase 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) - TOZ-PD
• Date of first enrolment: 12/04/2016
• Target sample size: 450
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-005630-60
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Canada, Czech Republic, European Union, Germany, Spain, United States

Contacts

• Name: Antero Kallio
• Affiliation: Biotie Therapies Corp.

• Name: Antero Kallio
• Affiliation: Biotie Therapies Corp.

Key inclusion & exclusion 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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 158
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 292

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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Parkinson’s Disease
MedDRA version: 20.0 Level: PT Classification code 10061536 Term: Parkinson's disease System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Product Name: Tozadenant
Product Code: SYN115
Pharmaceutical Form: Tablet
INN or Proposed INN: Tozadenant
CAS Number: 870070-55-6
Current Sponsor code: SYN115
Other descriptive name: TOZADENANT
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 60-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: The key secondary efficacy objectives of this study are:
1. To evaluate the effect of tozadenant on good ON time (defined as the sum of ON time without dyskinesia and ON time with non-troublesome dyskinesia).
2. To evaluate the effect of tozadenant on UPDRS Parts II (Activities of Daily Living [ADL] subscale) + III (motor subscale) total scores.

Primary end point(s): Primary Efficacy Endpoint (Part A):
The primary efficacy endpoint will be the change from Baseline to
Week 24 in the number of hours per day spent in the OFF state, as
assessed by patient-completed PD diaries and averaged over
3 consecutive days.

Main Objective: The primary efficacy objective of this study is to demonstrate the efficacy of the A2a receptor antagonist tozadenant in the treatment of levodopa-treated PD patients experiencing end-of-dose “wearing-off”, based on the change from Baseline to Week 24 in the number of hours per day spent in the OFF state.

Timepoint(s) of evaluation of this end point: Analysis of the Primary Efficacy Variable
The primary efficacy variable will be the change from Baseline to
Week 24 in the number of hours per day spent in the OFF state, as
assessed by patient-completed PD diaries and averaged over 3
consecutive days.

Secondary Outcome(s)

Secondary end point(s): Key Secondary Efficacy Endpoints (Part A):
1. Change from Baseline to Week 24 in the number of hours per day
spent in good ON time, defined as the sum of ON time without
dyskinesia and ON time with non-troublesome dyskinesia.
2. Change from Baseline to Week 24 on UPDRS Parts II (ADL subscale) + III (motor subscale) total scores.

Timepoint(s) of evaluation of this end point: Analysis of the key Secondary Efficacy Endpoints (Part A):
1. Change from Baseline to Week 24 in the number of hours per day
spent in good ON time, defined as the sum of ON time without
dyskinesia and ON time with non-troublesome dyskinesia.
2. Change from Baseline to Week 24 on UPDRS Parts II (ADL subscale) + III (motor subscale) total scores.

Secondary ID(s)

TOZ-CL05

2014-005630-60-DE

NCT02453386

Source(s) of Monetary Support

Biotie Therapies Inc.