Clinical Trial Results:
A Multicenter, Open-Label Study to Evaluate the Safety and Tolerability of Tozadenant as Adjunctive Therapy in Levodopa-Treated Patients with Parkinson’s Disease Experiencing End of Dose “Wearing-Off”
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Summary
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EudraCT number |
2016-003961-25 |
Trial protocol |
DE GB HU ES CZ IT |
Global end of trial date |
16 Jan 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
30 Jan 2019
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First version publication date |
30 Jan 2019
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
10TOZ-CL06
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03051607 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
IND Number: 78230 | ||
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Sponsors
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Sponsor organisation name |
Acorda Therapeutics
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Sponsor organisation address |
420 Saw Mill River Road, Ardsley, United States, 10502
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Public contact |
Christopher Kenny, Senior Vice President - Medical Affairs
, Acorda Therapeutics
, 914 326-5775, ckenney@acorda.com
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Scientific contact |
Christopher Kenny, Senior Vice President - Medical Affairs
, Acorda Therapeutics
, 914 326-5775, ckenney@acorda.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
16 Jan 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
16 Jan 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
16 Jan 2018
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To evaluate the safety and tolerability of tozadenant in levodopa-treated PD patients experiencing motor fluctuations.
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Protection of trial subjects |
Conduct of the study must be approved by an appropriately constituted IRB or IEC. Approval is required for the study protocol, investigational drug brochure, protocol amendments, informed consent forms, patient information sheets, and advertising materials. For each study patient, written informed consent will be obtained prior to any protocol-related activities. As part of this procedure, the principal investigator or one of his/her associates must explain orally and in writing the nature, duration, and purpose of the study, and the action of the drug in such a manner that the patient is aware of the potential risks, inconveniences, or adverse effects that may occur. The patient should be informed that he/she may withdraw from the study at any time, and the patient will receive all information that is required by local regulations and ICH guidelines. The principal investigator will provide the Sponsor or its representative with a copy of the IRB/IEC-approved informed consent form prior to the start of the study.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
25 May 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Spain: 1
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Country: Number of subjects enrolled |
United Kingdom: 6
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Country: Number of subjects enrolled |
Hungary: 1
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Country: Number of subjects enrolled |
Italy: 6
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Country: Number of subjects enrolled |
Canada: 1
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Country: Number of subjects enrolled |
United States: 51
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Worldwide total number of subjects |
66
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EEA total number of subjects |
14
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
27
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From 65 to 84 years |
39
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85 years and over |
0
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Recruitment
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Recruitment details |
A total of 66 patients were enrolled in 27 study centers across 6 countries and were included in the Safety Set (SS) as well as the Full Analysis Set (FAS). | ||||||||||||||||||
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Pre-assignment
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Screening details |
A total of 66 patients were enrolled in 27 study centers across 6 countries. | ||||||||||||||||||
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Period 1
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Period 1 title |
52 Weeks (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||
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Arms
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Arm title
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Tozadenant | ||||||||||||||||||
Arm description |
120 mg BID | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Tozadenant
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
120 mg BID Oral tablet
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Baseline characteristics reporting groups
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Reporting group title |
52 Weeks
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Reporting group description |
- | ||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Tozadenant
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Reporting group description |
120 mg BID | ||
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End point title |
The Safety and tolerability of Tozadenant in Levodopa-treated Parkinson Disease patients experiencing motor fluctuations. [1] | ||||||||||||||||||
End point description |
The primary objective of this study was to evaluate the safety and tolerability of tozadenant in levodopa-treated PD patients experiencing motor fluctuations. A total of 66 patients were enrolled in 27 study centers across 6 countries: USA, United Kingdom, Italy, Canada, Spain and Hungary, and were included in the Safety Set (SS). A total of 60 out of 66 enrolled patients completed up to Week 2, 44 completed Week 4, 22 completed Week 12, and 4 completed Week 24.
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End point type |
Primary
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End point timeframe |
24 Weeks due to early termination of study.
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics were provided for this study. |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Effects of Tozadenant on the Occurrence of Daytime Drowsiness by Using the Epworth Sleepiness Scale. | ||||||||||||||||||||||
End point description |
The Secondary objectives was to evaluate the effects of tozadenant on the occurrence of daytime drowsiness by using the Epworth Sleepiness scale. The Epworth Sleepiness Scale (ESS) is a scale intended to measure daytime sleepiness that is measured by use of a short questionnaire. A score within the range 0−9 is considered to be normal while a score within the range of 10−24 would indicate that medical help should be solicited. 60 out of 66 patients completed up to Week 2, 44 completed Week 4, 22 completed Week 12, and 4 completed Week 24.
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End point type |
Secondary
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End point timeframe |
24 Weeks due to early termination of study.
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| No statistical analyses for this end point | |||||||||||||||||||||||
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End point title |
Effects of Tozadenant on the Occurrence of Suicidality Using the Columbia-Suicide Severity Scale (C-SSRS) Summarized by Visit. | ||||||||||||||||||||||||||||||||||||||||||
End point description |
The Columbia Suicide Severity Rating Scale (C-SSRS) is an example of an acceptable instrument that maps to the Columbia Classification Algorithm for Suicide Assessment (C-CASA), directly classifying events of interest into one of 11 categories of suicidal ideation and behavior. Completion of the scale can be based entirely on patient interview, but integration of information from other sources (such as family and friends, significant others, caregivers, health professionals, and medical records) is also allowed.
A total of 60 out of 66 enrolled patients completed up to Week 2, 44 completed Week 4, 22 completed Week 12, and 4 completed Week 24.
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End point type |
Secondary
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End point timeframe |
24 Weeks due to early termination of study.
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||
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End point title |
Effects of Tozadenant on the occurrence of impulsive behavior - Modified Minnesota Impulse Disorder Interview (mMIDI) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The Minnesota Impulsive Disorders Interview (MIDI) 8 is a global instrument that includes questions for compulsive gambling, buying, and sexual behavior (as well as other disorders not reported to occur in PD).
The mMIDI consists of 5 modules: compulsive buying, compulsive gambling, compulsive eating, hypersexuality and punding.
Positive Answer: Any answer other than “no” on any question is considered a “yes”/positive answer.
Negative Module: A module is considered negative if the patient’s answer to a gateway (initial) question is “no” or if a patient answers “yes” to a gateway question and “no” to all of the remaining answers after the gateway question in that module.
Positive Module: A module is considered positive if a patient gives a positive answer (No = 0, rarely = 1, occasionally = 2, frequently = 3) to any question after the gateway (initial) question in one or more of the 5 modules.
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End point type |
Secondary
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End point timeframe |
24 Weeks due to early termination of study.
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
52 weeks but due to early termination subjects last visit was at Week 24.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.1
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Reporting groups
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Reporting group title |
Tozadenant
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 3% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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03 Feb 2017 |
Protocol Version 2.0
To clarify the exclusion criteria that subjects who have had DBS at least 12-months before screening visit are eligible to participate in the study.
To move mMIDI assessment from baseline to the screening visit so that the site has adequate time to rule out ICD prior to subjects performing baseline patient diaries.
120 mg tablet will be blue colored not white to off-white. |
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09 Oct 2017 |
Protocol Version 3.0
New exclusion criteria added:
Addition of lower limit of ANC at screening to avoid situation where criteria are met for both study drug withdrawal and continuation.
New endpoint added:
Fall questionnaire
Added discontinuation requirement that needs definition of severe granulocytopenia to avoid risk that continued study drug exposure could worsen neutrophil count further.
Added clarification for a scale (Non-motor Symptom Assessment Scale) to be collected in ON state.
Added new table to reflect the added hematology testing.
Visits added to allow for more frequent hemotology monitoring to closely monitor white blood cells and absolute neutrophil counts.
Addition of lower limit of ANC at screening to avoid situation where criteria are met for both study drug withdrawal and continuation.
Added a statement allowing for additional review of practice PD diaries and contact details.
Clarification of scales that should be performed during patient's ON state:
PDQ-39
EQ-5D-5L
Non-motor Symptom Assessment Scale
CG-II
PGI-I |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
