Safety and Efficacy Study of SYN115 in Parkinson's Patients Using Levodopa to Treat End of Dose Wearing Off

A Double-blind, Randomized, Placebo-controlled Study of the Safety and Efficacy of SYN115 as Adjunctive Therapy in Levodopa-treated Parkinson's Subjects With End of Dose Wearing Off

The purpose of this research study is to test the effect of SYN115 compared to placebo (a "sugar pill" that looks like SYN115 but does not include active drug) on movement during the "on" and "off" states as well as other symptoms that some patients with Parkinson's disease experience. This study will also look at whether or not patients with Parkinson's disease experience "side-effects" with SYN115.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: Tozadenant (SYN115) 60 mg BID; Drug: Levodopa (L-dopa); Drug: Tozadenant (SYN115) 120 mg BID; Drug: Tozadenant (SYN115) 180 mg BID; Drug: Tozadenant (SYN115) 240 mg BID; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 420
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
  • Santa Fe, Argentina
• Canada
  • Alberta
    • Edmonton, Alberta, Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada
  • Ontario
    • Ottawa, Ontario, Canada
  • Quebec
    • Montreal, Quebec, Canada
    • Quebec City, Quebec, Canada
• Chile
  • Santiago, Chile
  • Valdivia, Chile
• Romania
  • Brasov, Romania
  • Bucharest, Romania
  • Constanta, Romania
  • Timisoara, Romania
  • Târgu-Mureş, Romania
• Ukraine
  • Dnipropetrovsk, Ukraine
  • Donetsk, Ukraine
  • Kiev, Ukraine
  • Lviv, Ukraine
  • Poltava, Ukraine
  • Vinnytsia, Ukraine
  • Zaporizhzhya, Ukraine
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35005
  • California
    • La Jolla, California, United States, 92037
    • Loma Linda, California, United States, 92318
    • Los Angeles, California, United States, 90001
    • Oxnard, California, United States, 93030
    • San Francisco, California, United States, 94016
  • Colorado
    • Denver, Colorado, United States, 80014
  • Connecticut
    • Manchester, Connecticut, United States, 06040
    • New Haven, Connecticut, United States, 06501
  • Florida
    • Boca Raton, Florida, United States, 33427
    • Gainesville, Florida, United States, 32601
    • Miami, Florida, United States, 33101
    • Tampa, Florida, United States, 33601
    • Weston, Florida, United States, 33326
  • Georgia
    • Atlanta, Georgia, United States, 30301
    • Augusta, Georgia, United States, 30901
  • Idaho
    • Boise, Idaho, United States, 83701
  • Illinois
    • Springfield, Illinois, United States, 62629
  • Indiana
    • Indianapolis, Indiana, United States, 46077
  • Iowa
    • Des Moines, Iowa, United States, 50047
  • Kansas
    • Kansas City, Kansas, United States, 66012
  • Kentucky
    • Lexington, Kentucky, United States, 40502
  • Maryland
    • Baltimore, Maryland, United States, 21201
  • Michigan
    • West Bloomfield, Michigan, United States, 48302
  • Minnesota
    • Minneapolis, Minnesota, United States, 55111
  • New York
    • Commack, New York, United States, 11725
    • New York, New York, United States, 10001
  • North Carolina
    • Durham, North Carolina, United States, 27517
  • Ohio
    • Cincinnati, Ohio, United States, 41073
    • Cleveland, Ohio, United States, 44101
    • Columbus, Ohio, United States, 43004
    • Toledo, Ohio, United States, 43460
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74008
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18001
    • Philadelphia, Pennsylvania, United States, 19019
  • South Carolina
    • Charleston, South Carolina, United States, 29401
  • Texas
    • Dallas, Texas, United States, 75001
    • Houston, Texas, United States, 77001
  • Virginia
    • Roanoke, Virginia, United States, 24001
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53201

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Meet Parkinson's Disease (PD) diagnosis consistent with UK PD diagnostic criteria
• Meet Hoehn and Yahr PD stage
• Good response to levodopa
• Stable regimen of anti-parkinson medications
• Are able to complete a Parkinson's disease diary
• If of childbearing potential(male and female), use an acceptable method of birth control
• Able and willing to sign an IRB/IEC approved informed consent
• Able and willing to understand study requirements, follow study instructions, attend all visits and undergo all planned tests.

Exclusion Criteria:

• Secondary or atypical Parkinson's
• Neurosurgical intervention for Parkinson's disease
• Treatment with apomorphine
• Treatment with anti-psychotic drugs
• Other abnormal findings on physical or neuro exam or history that in the opinion of the investigator would make subject unsuitable for the study or prejudice safety and efficacy evaluation
• MMSE less than 26
• Subjects with untreated or uncontrolled current episode of major depression
• Receipt of any anti-psychotic drugs greater than 1 month in the past 5 years or any exposure in past year (except for quetiapine at doses <100mg per day)
• Women pregnant or lactating
• History of hepatitis, cholangitis
• Untreated or uncontrolled hypothyroidism or hyperthyroidism
• Drops in blood pressure requiring medication to maintain blood pressure
• Any clinically significant out of range laboratory evaluations
• Known sensitivity to the study medication or its components
• Suicide ideation or type 4 or type 5 on the Columbia suicide severity rating scale
• Finding of malignant melanoma on full body skin exam
• Impulse disorder conditions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tozadenant (SYN115) 60 mg BID; Tozadenant tablets, white-coated, modified-oval tablets manufactured in 60 mg dosage strengths.	Drug: Tozadenant (SYN115) 60 mg BID; Tozadenant tablets, white-coated, modified-oval tablets manufactured in 60 mg dosage strengths. Total daily doses include 60 mg BID.; Drug: Levodopa (L-dopa); One intravenous infusion of L-dopa to reach approximately 600 ng/ ml plasma concentration.; Other Names: L-dopa
Experimental: Tozadenant (SYN115) 120 mg BID; Tozadenant tablets, white-coated, modified-oval tablets manufactured in 60 mg dosage strengths.	Drug: Levodopa (L-dopa); One intravenous infusion of L-dopa to reach approximately 600 ng/ ml plasma concentration.; Other Names: L-dopa; Drug: Tozadenant (SYN115) 120 mg BID; Tozadenant tablets, white-coated, modified-oval tablets manufactured in 60 mg dosage strengths. Total daily doses include 120 mg BID.
Experimental: Tozadenant (SYN115) 180 mg BID; Tozadenant tablets, white-coated, modified-oval tablets manufactured in 60 mg dosage strengths.	Drug: Levodopa (L-dopa); One intravenous infusion of L-dopa to reach approximately 600 ng/ ml plasma concentration.; Other Names: L-dopa; Drug: Tozadenant (SYN115) 180 mg BID; Tozadenant tablets, white-coated, modified-oval tablets manufactured in 60 mg dosage strengths. Total daily doses include 180 mg BID.
Experimental: Tozadenant (SYN115) 240 mg BID; Tozadenant tablets, white-coated, modified-oval tablets manufactured in 60 mg dosage strengths.	Drug: Levodopa (L-dopa); One intravenous infusion of L-dopa to reach approximately 600 ng/ ml plasma concentration.; Other Names: L-dopa; Drug: Tozadenant (SYN115) 240 mg BID; Tozadenant tablets, white-coated, modified-oval tablets manufactured in 60 mg dosage strengths. Total daily doses include 240 mg BID.
Placebo Comparator: Sugar Pill; White-coated, modified-oval placebo tablets.	Drug: Levodopa (L-dopa); One intravenous infusion of L-dopa to reach approximately 600 ng/ ml plasma concentration.; Other Names: L-dopa; Drug: Placebo; White-coated, modified-oval placebo tablets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Assess efficacy of different doses of SYN115 for reducing the mean total hours of awake time per day spent in the off state	12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
To assess the effect of SYN115 on dyskinesia	12 weeks
To assess the effect of SYN115 on UPDRS scores	12 weeks
To assess investigator and patient impressions of PD severity and change	12 weeks
To assess the effect of SYN115 on non motor symptoms of PD	12 weeks
To assess the safety and tolerability of SYN115	12 weeks
To assess the effects of SYN115 on daytime drowsiness, impulsive behavior, development of melanoma and suicidal ideation	12 weeks

Collaborators and Investigators

• Sponsor: Biotie Therapies Inc.
• Investigators: Study Chair: Steve Bandak, MD, Biotie Therapies Inc.; Study Director: Ann Neale, RN, Biotie Therapies Inc.

Publications and helpful links

General Publications

• Hauser RA, Olanow CW, Kieburtz KD, Pourcher E, Docu-Axelerad A, Lew M, Kozyolkin O, Neale A, Resburg C, Meya U, Kenney C, Bandak S. Tozadenant (SYN115) in patients with Parkinson's disease who have motor fluctuations on levodopa: a phase 2b, double-blind, randomised trial. Lancet Neurol. 2014 Aug;13(8):767-76. doi: 10.1016/S1474-4422(14)70148-6. Epub 2014 Jul 6.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: January 24, 2011
• First Submitted That Met QC Criteria: January 24, 2011
• First Posted (Estimate): January 26, 2011

Study Record Updates

• Last Update Posted (Actual): January 17, 2019
• Last Update Submitted That Met QC Criteria: January 14, 2019
• Last Verified: May 1, 2014

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; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Levodopa
• Other Study ID Numbers: SYN115-CL02