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

Idiopathic Parkinson's Disease Clinical Trial

— 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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02453386
• Other study ID #: TOZ-CL05
• Secondary ID: 2014-005630-60
• Status: Terminated
• Phase: Phase 3
• Start date: July 2015
• Est. completion date: January 12, 2018

Study information

• Verified date: March 2019
• Source: Biotie Therapies Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 449
• Est. completion date: January 12, 2018
• Est. primary completion date: January 12, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Idiopathic Parkinson's Disease
• Parkinson Disease

Intervention

Drug:
• tozadenant

• placebo

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Biotie Therapies Inc.

Countries where clinical trial is conducted

United States,  Austria,  Canada,  Czechia,  Germany,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Global Assessments of Improvement: Clinical Global Impression of Improvement (CGI-I) 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.	At Week 24
Other	Patient Global Impression of Improvement (PGI-I) 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.	At Week 24
Primary	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.	Baseline to 24 Weeks
Secondary	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.	Baseline to 24 Weeks
Secondary	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.	Baseline to Week 24
Secondary	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.	Baseline to Week 24