Study to Evaluate SYN115 in Parkinson's Disease

A Randomized, Double-blind, Placebo Controlled, Two-way Cross-over Study to Explore the Effects of 7 Days of Dosing With SYN115 20 mg p.o. BID or 60 mg p.o. BID on Clinical and fMRI Response to Intravenous Levodopa in Patients With Mild to Moderate Parkinson's Disease

This is an exploratory study to evaluate if SYN115 has an effect on Parkinson's disease as measured by clinical symptoms and brain images using magnetic resonance imaging (MRI) when a function test is administered.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: Tozadenant; Drug: Placebo

Detailed Description

This is a randomized, double-blind, placebo-controlled, two-way crossover study in which each patient will act as their own control. Each patient enrolled will receive both SYN115 (20 mg or 60 mg) and placebo separated by a minimum of one week washout between periods. An adaptive design will be used to determine if SYN115 elicits effects relevant to PD in the fewest number of patients by performing interim analyses in successive cohorts of patients receiving 60 or 20 mg.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University St. Louis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of Parkinson's disease
• Hoen and Yahr stage 1-3
• On stable dose of anti-parkinsons treatment for 30 days prior to screening
• Age 40 to 75 years
• Sign an IRB approved informed consent
• Men and women agree to use adequate birth control
• ECG measurements are within normal limits
• Able to understand study requirements

Exclusion Criteria:

• Secondary Parkinson's (drug induced or post stroke)
• Received treatment with other investigational drug 30 days prior to study entry
• Using disallowed medications
• Significant neurological illness other than Parkinson's
• IQ less than 70 on IQ test
• MMSE score < or = 23
• History of psychosis or on anti-psychotic medication
• Current serious medical illness
• History of substance abuse
• History of head injury with loss of consciousness
• History of brain surgery
• Contraindications to MRI like claustrophobia, metal implants or other implantable devices
• Abnormal liver function tests and/or hepatitis or cholangitis
• Gilberts disease
• Pregnant or nursing
• Known hypersensitivity to SYN115

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Active medication Tozadenant 20 mg oral capsules with a daily dosage of either 20 mg BID or 60 mg BID	Drug: Tozadenant; 20 mg oral capsules with a daily dosage of either 20 mg BID or 60 mg BID; Other Names: SYN115; A2a antagonist
Placebo Comparator: 2; Crossover from arm 1 to arm 2 with one week washout. One of the arms is placebo control	Drug: Placebo; Placebo oral capsules Placebo for 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
This is an exploratory study to evaluate effects of SYN115 in patients with PD, as determined by clinical and fMRI evaluation. The results of this initial study will help determine the range to be used in subsequent studies.	Before treatment and at the end of each treatment period

Secondary Outcome Measures

Outcome Measure	Time Frame
Pittsburgh side effect scale	Before, after the first dose and end of each treatment period
VAS for overall well being, dizziness/light-headedness, nausea/vomiting, mood anxiety	Before, after the first dose and end of each treatment period
Measurement of motor symptoms of Parkinson's disease and tapping speed	Before, after the first dose and end of each treatment period

Collaborators and Investigators

• Sponsor: Biotie Therapies Inc.
• Investigators: Study Chair: Steve Bandak, MB BS MRCP, Synosia Therapeutics; Study Director: Ann Neale, RN, Synosia Therapeutics; Study Chair: Uwe Meya, MD, Synosia Therapeutics

Publications and helpful links

General Publications

• Black KJ, Campbell MC, Dickerson W, Creech ML, Koller JM, Chung SC, Bandak SI: A randomized, double-blind, placebo-controlled cross-over trial of the adenosine 2a antagonist SYN115 in Parkinson disease. Neurology 74(9): A317, 2010.
• Black KJ, Koller JM, Campbell MC, Gusnard DA, Bandak SI. Quantification of indirect pathway inhibition by the adenosine A2a antagonist SYN115 in Parkinson disease. J Neurosci. 2010 Dec 1;30(48):16284-92. doi: 10.1523/JNEUROSCI.2590-10.2010.

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): May 1, 2009
• Study Completion (Actual): May 1, 2009

Study Registration Dates

• First Submitted: January 15, 2008
• First Submitted That Met QC Criteria: January 30, 2008
• First Posted (Estimate): January 31, 2008

Study Record Updates

• Last Update Posted (Actual): August 8, 2017
• Last Update Submitted That Met QC Criteria: August 3, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: SYN115-CL01