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

NCT02453386 | Terminated Phase 3 Results DMC

• 2 other identifiers: TOZ-CL052014-005630-60
• Study Type: interventional
• Target: 449
• Locations: 7 countries
• Sites: 71

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).

Conditions

Idiopathic Parkinson's Disease

Keywords

Motor fluctuations; Off time; On time; Dyskinesia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Change in Good ON Time From Baseline to Week 24

  Baseline to 24 Weeks

• Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Activities of Daily Living (ADL) Subscale + Part III Motor Function

  Baseline to Week 24

• Change From Baseline to Week 24 in the ON State in Unified Parkinson's Disease Rating Scale (UPDRS) Part IIl

  Baseline to Week 24

Other Outcomes (2)

• Global Assessments of Improvement: Clinical Global Impression of Improvement (CGI-I) Week 24

  At Week 24

• Patient Global Impression of Improvement (PGI-I) Week 24

  At Week 24

Study Arms (3)

Tozadenant 60 mg BID

EXPERIMENTAL

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.

Drug: tozadenant

Tozadenant 120 mg BID

EXPERIMENTAL

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.

Drug: tozadenant

Placebo BID

PLACEBO COMPARATOR

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.

Drug: placebo

Interventions

tozadenant DRUG

Also known as: SYN115

Tozadenant 120 mg BID; Tozadenant 60 mg BID

placebo DRUG

Also known as: tozadenant placebo

Placebo BID

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Biotie Therapies Inc.: lead

Study Sites (71)

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Birmingham, Alabama, 35005, United States

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Sun City, Arizona, 85351, United States

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Loma Linda, California, 92318, United States

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Los Angeles, California, 90001, United States

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Oxnard, California, 93030, United States

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Reseda, California, 91335, United States

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Sacramento, California, 914203, United States

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Sunnyvale, California, 94043, United States

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Englewood, Colorado, 80110, United States

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Vernon, Connecticut, 06029, United States

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Boca Raton, Florida, 33428, United States

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Gainesville, Florida, 32601, United States

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Jacksonville, Florida, 32034, United States

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Tampa, Florida, 33601, United States

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Atlanta, Georgia, 30301, United States

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Augusta, Georgia, 30805, United States

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Chicago, Illinois, 60007, United States

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Kansas City, Kansas, 66012, United States

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Lexington, Kentucky, 40502, United States

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Baltimore, Maryland, 21201, United States

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Boston, Massachusetts, 02101, United States

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East Lansing, Michigan, 48808, United States

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Farmington Hills, Michigan, 48167, United States

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West Bloomfield, Michigan, 48302, United States

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St Louis, Missouri, 63101, United States

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Albany, New York, 12084, United States

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Commack, New York, 11725, United States

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Rochester, New York, 14602, United States

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Asheville, North Carolina, 28715, United States

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Durham, North Carolina, 27517, United States

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Cincinnati, Ohio, 41073, United States

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Cleveland, Ohio, 44101, United States

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Toledo, Ohio, 43460, United States

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Tulsa, Oklahoma, 74008, United States

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Philadelphia, Pennsylvania, 19019, United States

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Nashville, Tennessee, 37011, United States

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Houston, Texas, 77001, United States

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Burlington, Vermont, 05401, United States

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Roanoke, Virginia, 24001, United States

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Kirkland, Washington, 98033, United States

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Innsbruck, Austria

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Vienna, Austria

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Edmonton, Alberta, Canada

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Ottawa, Ontario, Canada

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Toronto, Ontario, Canada

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Brno, Czechia

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Choceň, Czechia

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Pardubice, Czechia

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Prague, Czechia

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Rychnov nad Kněžnou, Czechia

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Beelitz-Heilstätten, Germany

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Berlin, Germany

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Dresden, Germany

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Haag in Oberbayern, Germany

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Marburg, Germany

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Ulm, Germany

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Arcugnano, Italy

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Cassino, Italy

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Chieti, Italy

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Grosseto, Italy

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Pavia, Italy

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Pisa, Italy

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Rome, Italy

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Salerno, Italy

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Venice, Italy

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Manresa, Barcelona, Spain

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Sant Cugat del Vallès, Barcelona, Spain

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Terrassa, Barcelona, Spain

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Donostia / San Sebastian, Guipuzcoa, Spain

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Barcelona, Spain

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Madrid, Spain

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MeSH Terms

Conditions

Parkinson Disease; Dyskinesias

Interventions

tozadenant

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Christopher Kenney, Senior Vice President - Medical Affairs
• Organization: Acorda Therapeutics

ckenney@acorda.com

914-326-5775

Study Officials

• Christopher Kenney, MD

  Biotie Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2015
• First Posted: May 25, 2015
• Study Start: July 1, 2015
• Primary Completion: January 12, 2018
• Study Completion: January 12, 2018
• Last Updated: April 3, 2019
• Results First Posted: March 26, 2019

Record last verified: 2019-03

Locations

US (40); CZ (5); DE (6); IT (9); ES (6); AU (2); CA (3)