Safety and Tolerability of Tozadenant as Adjunctive Therapy in Levodopa-Treated Patients With Parkinson's Disease.

• Sponsor: Biotie Therapies Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03051607
• Collaborator: Acorda Therapeutics (Industry)
• Enrollment: 66
• Locations: 35
• Arm: 1
• Actual Duration (Months): 9.2
• Patients Per Site: 1.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Phase 3, international, multicenter, open-label 12 month safety study.

Condition or Disease	Intervention/Treatment	Phase
Idiopathic Parkinson Disease	Drug: Tozadenant	Phase 3

Detailed Description

Each patient will participate for up to 52 weeks, which includes a Screening Period, followed by a Baseline Visit and open-label treatment for 1 year with a safety Follow-up 4 weeks after the last treatment.

• Screening Period: up to 6 weeks.

• Open-Label Treatment Period: 52 weeks (1 year)

• Post-Treatment Safety Follow Up: 4 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 66 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Eligible patients will begin dosing with tozadenant at a dose of 120 mg twice daily. At Week 2 or thereafter, the investigator may adjust the patient's IMP dose as clinically indicated; doses of 60 mg BID and 120 mg BID will be permitted.Eligible patients will begin dosing with tozadenant at a dose of 120 mg twice daily. At Week 2 or thereafter, the investigator may adjust the patient's IMP dose as clinically indicated; doses of 60 mg BID and 120 mg BID will be permitted.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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"
• Actual Study Start Date: Apr 10, 2017
• Actual Primary Completion Date: Jan 16, 2018
• Actual Study Completion Date: Jan 16, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tozadenant 120 mg twice daily. At Week 2 or thereafter doses of 60 mg BID and 120 mg BID will be permitted.	Drug: Tozadenant; 1 Year Open Label, 120 mg BID tozadenant, with dose modification to 60 mg BID tozadenant permitted.; Other Names: SYN115

Outcome Measures

Primary Outcome Measures

1. To Evaluate the Safety and Tolerability of Tozadenant in Levodopa-treated PD Patients Experiencing Motor Fluctuations. [Up to 28 Weeks including safety follow-up visit.]

   The primary objective of this study was to evaluate the safety and tolerability of tozadenant in levodopa-treated Parkinson's Disease (PD) patients experiencing motor fluctuations, based on assessment of treatment-emergent adverse events (TEAEs), vital signs, electrocardiograms (ECGs), and clinical laboratory tests. 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).

Secondary Outcome Measures

1. To Evaluate the Effects of Tozadenant on the Occurrences of Daytime Drowsiness by Using the Epworth Sleepiness Scale. [Up to 28 Weeks including safety follow-up visit.]

   The Epworth Sleepiness Scale (ESS) is a scale intended to measure daytime sleepiness that is measured by use of a short questionnaire. Minimum range is 0 - Maximum range is 24. 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.

2. To Evaluate the Effects of Tozadenant on the Number of Participants With Suicidal Ideation or Behavior Using the Columbia-Suicide Severity Scale (C-SSRS) Summarized by Visit. [Up to 28 Weeks including safety follow-up visit.]

   The Columbia Suicide Severity Rating Scale (C-SSRS) is a standardized suicidality rating system. The interview measures presence of suicidality and consists of 4 categories: suicidal ideation, intensity of ideation, suicidal behavior, and actual/potential lethality. Suicidal Ideation - A series of 1 -5 questions with 5 types of ideation of increasing severity. Score of Yes = 1, No= 0. A positive answer to question 4 (active suicidal ideation with some intent to act) or 5 (active suicidal ideation with specific plan and intent) indicates that the individual has some intent to act on suicidal thoughts and will need further evaluation. Suicidal Behavior - Different types of suicidal behavior are scored (Yes=1, No=0) and identify the occurrence of actual, interrupted, or aborted attempts; preparatory behaviors; and suicide. The total number of each type of suicidal behavior show the density of suicide, (more behaviors represent a higher degree of risk).

3. To Evaluate the Effects of Tozadenant on the Number of Participants With Occurrence of Impulsive Behavior - Modified Minnesota Impulse Disorder Interview (mMIDI) [Up to 28 Weeks including safety follow-up visit.]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 (except DBS if electrode placement has been performed over 12 months prior to screening)

• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Barrow Neurology Clinics, St. Joseph's Hospital and Medical Center, Dignity Health	Phoenix	Arizona	United States	85013
2	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	77215
3	Collaborative Neuroscience Network, LLC	Long Beach	California	United States	90802
4	USC, Keck School of Medicine	Los Angeles	California	United States	90089
5	SC3 Research Group	Pasadena	California	United States	91105
6	JEM Research Institute	Atlantis	Florida	United States	33462
7	Aventura Neurologic Associates	Aventura	Florida	United States	33180
8	Parkinson's Disease and Movement Disorders Center of Boca Raton	Boca Raton	Florida	United States	33486
9	Neurology Associates, P.A.	Maitland	Florida	United States	32751
10	Neurology Associates of Ormond Beach	Ormond Beach	Florida	United States	32174
11	Parkinson's Disease Treatment Center of SW Florida	Port Charlotte	Florida	United States	33980
12	Infinity Clinical Research	Sunrise	Florida	United States	33513
13	Hawaii Pacific Neuroscience	Honolulu	Hawaii	United States	96817
14	Unity Point Health	Des Moines	Iowa	United States	10034
15	Unity Point Health	Des Moines	Iowa	United States	50312
16	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
17	University of Kentucky, Department of Neurology	Lexington	Kentucky	United States	40536
18	Henry Ford West Bloomfield Hospital	Bloomfield Hills	Michigan	United States	48322
19	Struthers Parkinson's Center	Golden Valley	Minnesota	United States	55416
20	Struthers Parkinson's Center	Golden Valley	Minnesota	United States	55427
21	The Robert and John M. Bendheim Parkinson and Movement Disorders Center	New York	New York	United States	10029
22	Asheville Neurology Specialists, PA	Asheville	North Carolina	United States	28806
23	Raleigh Neurology Associates	Raleigh	North Carolina	United States	27607
24	Movement Disorders Clinic of Oklahoma	Tulsa	Oklahoma	United States	74136
25	Abington Neurological Associates	Willow Grove	Pennsylvania	United States	27607
26	Baylor College of Medicine	Houston	Texas	United States	77030
27	University of Virginia, Department of Neurology	Charlottesville	Virginia	United States	98034
28	Booth Gardner Parkinson's Care Center	Kirkland	Washington	United States	98034
29	Premier Clinical Research	Spokane	Washington	United States	99202
30	University of Wisconsin-Madison	Madison	Wisconsin	United States	53705
31	University of Wisconsin - Madison	Madison	Wisconsin	United States	53706
32	Ottawa Hospital Research Institute	Ottawa	Ontario	Canada	K1Y 4E9
33	The Walton Centre NHS Foundation Trust, Neuroscience Research Center	Liverpool	England	United Kingdom	L9 7U
34	Newcastle University Clinical Ageing Research Unit (CARU)	Newcastle upon Tyne	England	United Kingdom	NE4 5PL
35	The Queen Elizabeth University Hospital Department of Neurology	Glasgow	Scottland	United Kingdom	G51 4TF

Sponsors and Collaborators

• Biotie Therapies Inc.
• Acorda Therapeutics

Investigators

• Study Director: Christopher Kenney, MD, Acorda Therapeutics

Study Documents (Full-Text)

• Study Protocol - Oct 9, 2017
• Statistical Analysis Plan - Feb 13, 2018

More Information

Publications

None provided.

• Responsible Party: Biotie Therapies Inc.
• ClinicalTrials.gov Identifier: NCT03051607
• Other Study ID Numbers: TOZ-CL06
• First Posted: Feb 13, 2017
• Last Update Posted: May 3, 2019
• Last Verified: Apr 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Biotie Therapies Inc.: Motor Fluctuations; Off time; On time; Dyskinesia
• Additional relevant MeSH terms: Parkinson Disease

Study Results

Participant Flow

Recruitment Details	The disposition of study patients. 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) as well as the Full Analysis Set (FAS).

Arm/Group Title	Tozadenant
Arm/Group Description	120 mg twice daily. At Week 2 or thereafter doses of 60 mg BID and 120 mg BID will be permitted. Tozadenant: 1 Year Open Label, 120 mg BID tozadenant, with dose modification to 60 mg BID tozadenant permitted.
Period Title: Overall Study
STARTED	66
COMPLETED	0
NOT COMPLETED	66

Baseline Characteristics

Arm/Group Title	Tozadenant
Arm/Group Description	120 mg twice daily. At Week 2 or thereafter doses of 60 mg BID and 120 mg BID will be permitted. Tozadenant: 1 Year Open Label, 120 mg BID tozadenant, with dose modification to 60 mg BID tozadenant permitted.
Overall Participants	66
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	27 40.9%
>=65 years	39 59.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.8 (8.14)
Sex: Female, Male (Count of Participants)
Female	16 24.2%
Male	50 75.8%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	61 92.4%
Black or African American	1 1.5%
Asian	3 4.5%
American Indian or Alaska Native	1 1.5%
Hispanic or Latino	6 9.1%
Not Hispanic or Latino	60 90.9%
Region of Enrollment (Count of Participants)
United States	51 77.3%
United Kingdom	6 9.1%
Canada	1 1.5%
Spain	1 1.5%
Hungary	1 1.5%
Italy	6 9.1%
Weight at Screening (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	80.4 (17.18)

Outcome Measures

1. Primary Outcome

Title	To Evaluate the Safety and Tolerability of Tozadenant in Levodopa-treated PD Patients Experiencing Motor Fluctuations.
Description	The primary objective of this study was to evaluate the safety and tolerability of tozadenant in levodopa-treated Parkinson's Disease (PD) patients experiencing motor fluctuations, based on assessment of treatment-emergent adverse events (TEAEs), vital signs, electrocardiograms (ECGs), and clinical laboratory tests. 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).
Time Frame	Up to 28 Weeks including safety follow-up visit.

Outcome Measure Data

Analysis Population Description

Safety evaluation was based on Safety Set which included all 66 patients enrolled in the study.

Arm/Group Title	Tozadenant
Arm/Group Description	120 mg twice daily. At Week 2 or thereafter doses of 60 mg BID and 120 mg BID will be permitted. Tozadenant: 1 Year Open Label, 120 mg BID tozadenant, with dose modification to 60 mg BID tozadenant permitted.
Measure Participants	66
Subjects with at least one treatment-emergent AE	46 69.7%
Subjects with at least one related TEAE	33 50%
Subjects discontinuing study drug due to an AE	7 10.6%
Subjects with at least one SAE	5 7.6%
Subjects with at least one life-threatening SAE	5 7.6%
Subjects with AE leading to death	2 3%

2. Secondary Outcome

Title	To Evaluate the Effects of Tozadenant on the Occurrences of Daytime Drowsiness by Using the Epworth Sleepiness Scale.
Description	The Epworth Sleepiness Scale (ESS) is a scale intended to measure daytime sleepiness that is measured by use of a short questionnaire. Minimum range is 0 - Maximum range is 24. 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.
Time Frame	Up to 28 Weeks including safety follow-up visit.

Outcome Measure Data

Analysis Population Description

Planned patient enrollment numbers were not achieved as this study and the tozadenant development program were terminated early, based on an unexpected emerging safety signal. No patient completed the 52 Week study treatment period prior to Sponsor termination of the study.

Arm/Group Title	Tozadenant
Arm/Group Description	120 mg twice daily. At Week 2 or thereafter doses of 60 mg BID and 120 mg BID will be permitted. Tozadenant: 1 Year Open Label, 120 mg BID tozadenant, with dose modification to 60 mg BID tozadenant permitted.
Measure Participants	66
Baseline	7.9 (5.32)
Week 2	7.4 (5.29)
Week 6	8.5 (4.72)
Week 12	10.0 (3.53)
Week 24	12.0 (4.08)
Early Termination	7.9 (5.08)
Safety Follow-up	7.3 (4.95)

3. Secondary Outcome

Title	To Evaluate the Effects of Tozadenant on the Number of Participants With Suicidal Ideation or Behavior Using the Columbia-Suicide Severity Scale (C-SSRS) Summarized by Visit.
Description	The Columbia Suicide Severity Rating Scale (C-SSRS) is a standardized suicidality rating system. The interview measures presence of suicidality and consists of 4 categories: suicidal ideation, intensity of ideation, suicidal behavior, and actual/potential lethality. Suicidal Ideation - A series of 1 -5 questions with 5 types of ideation of increasing severity. Score of Yes = 1, No= 0. A positive answer to question 4 (active suicidal ideation with some intent to act) or 5 (active suicidal ideation with specific plan and intent) indicates that the individual has some intent to act on suicidal thoughts and will need further evaluation. Suicidal Behavior - Different types of suicidal behavior are scored (Yes=1, No=0) and identify the occurrence of actual, interrupted, or aborted attempts; preparatory behaviors; and suicide. The total number of each type of suicidal behavior show the density of suicide, (more behaviors represent a higher degree of risk).
Time Frame	Up to 28 Weeks including safety follow-up visit.

Outcome Measure Data

Analysis Population Description

Planned patient enrollment numbers were not achieved as this study and the tozadenant development program were terminated early, based on an unexpected emerging safety signal. No patient completed the 52 Week study treatment period prior to Sponsor termination of the study.

Arm/Group Title	Tozadenant
Arm/Group Description	120 mg twice daily. At Week 2 or thereafter doses of 60 mg BID and 120 mg BID will be permitted. Tozadenant: 1 Year Open Label, 120 mg BID tozadenant, with dose modification to 60 mg BID tozadenant permitted.
Measure Participants	66
Screening - Lifetime: Actual attempts	2 3%
Screening - Lifetime: Interrupted attempts	2 3%
Screening - Lifetime: Aborted attempts	3 4.5%
Screening - Past 5 years: Actual attempts	2 3%
Screening - Past 5 years: Interrupted attempts	2 3%
Screening - Past 5 years: Aborted attempts	2 3%
Screening - Past 6 months: Actual attempts	2 3%
Screening - Past 6 months: Interrupted attempts	2 3%
Screening - Past 6 months: Aborted attempts	2 3%
Baseline - Since last visit: Actual attempts	3 4.5%
Baseline - Since last visit: Interrupted attempts	2 3%
Baseline - Since last visit: Aborted attempts	3 4.5%
Week 2 - Since last visit: Actual attempts	3 4.5%
Week 2 - Since last visit: Interrupted attempts	3 4.5%
Week 2 - Since last visit: Aborted attempts	3 4.5%
Week 6 - Since last visit: Actual attempts	1 1.5%
Week 6 - Since last visit: Interrupted attempts	1 1.5%
Week 6 - Since last visit: Aborted attempts	1 1.5%
Week 12 - Since last visit: Actual attempts	1 1.5%
Week 12 - Since last visit: Interrupted attempts	1 1.5%
Week 12 - Since last visit: Aborted attempts	1 1.5%
Week 24 - Since last visit: Actual attempts	1 1.5%
Week 24 - Since last visit: Interrupted attempts	1 1.5%
Week 24 - Since last visit: Aborted attempts	1 1.5%
Early Termination: Actual attempts	10 15.2%
Early Termination: Interrupted attempts	10 15.2%
Early Termination: Aborted attempts	10 15.2%
Safety Follow-up: Actual attempts	8 12.1%
Safety Follow-up: Interrupted attempts	8 12.1%
Safety Follow-up: Aborted attempts	11 16.7%

4. Secondary Outcome

Title	To Evaluate the Effects of Tozadenant on the Number of Participants With Occurrence of Impulsive Behavior - Modified Minnesota Impulse Disorder Interview (mMIDI)
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.
Time Frame	Up to 28 Weeks including safety follow-up visit.

Outcome Measure Data

Analysis Population Description

Planned patient enrollment numbers were not achieved as this study and the tozadenant development program were terminated early, based on an unexpected emerging safety signal. No patient completed the 52 Week study treatment period prior to Sponsor termination of the study. .

Arm/Group Title	Tozadenant
Arm/Group Description	120 mg twice daily. At Week 2 or thereafter doses of 60 mg BID and 120 mg BID will be permitted. Tozadenant: 1 Year Open Label, 120 mg BID tozadenant, with dose modification to 60 mg BID tozadenant permitted.
Measure Participants	66
Negative	66 100%
Positive	0 0%
Negative	59 89.4%
Positive	1 1.5%
Negative	43 65.2%
Positive	1 1.5%
Negative	22 33.3%
Positive	0 0%
Negative	4 6.1%
Positive	0 0%
Negative	60 90.9%
Positive	2 3%
Negative	56 84.8%
Positive	1 1.5%
Negative	65 98.5%
Positive	1 1.5%
Negative	59 89.4%
Positive	1 1.5%
Negative	44 66.7%
Positive	0 0%
Negative	22 33.3%
Positive	0 0%
Negative	4 6.1%
Positive	0 0%
Negative	61 92.4%
Positive	1 1.5%
Negative	56 84.8%
Positive	1 1.5%
Negative	66 100%
Positive	0 0%
Negative	60 90.9%
Positive	0 0%
Negative	44 66.7%
Positive	0 0%
Negative	22 33.3%
Positive	0 0%
Negative	4 6.1%
Positive	0 0%
Negative	60 90.9%
Positive	2 3%
Negative	56 84.8%
Positive	1 1.5%
Negative	66 100%
Positive	0 0%
Negative	60 90.9%
Positive	0 0%
Negative	43 65.2%
Positive	1 1.5%
Negative	22 33.3%
Positive	0 0%
Negative	4 6.1%
Positive	0 0%
Negative	61 92.4%
Positive	1 1.5%
Negative	57 86.4%
Positive	0 0%
Negative	66 100%
Positive	0 0%
Negative	60 90.9%
Positive	0 0%
Negative	44 66.7%
Positive	0 0%
Negative	22 33.3%
Positive	0 0%
Negative	4 6.1%
Positive	0 0%
Negative	62 93.9%
Positive	0 0%
Negative	57 86.4%
Positive	0 0%

Adverse Events

Time Frame	This study and the tozadenant development program were terminated early, based on an unexpected emerging safety signal. Due to Sponsor termination of the study, Adverse Events were collected up to Week 24.
Arm/Group Title	Tozadenant
Arm/Group Description	120 mg twice daily. At Week 2 or thereafter doses of 60 mg BID and 120 mg BID will be permitted. Tozadenant: 1 Year Open Label, 120 mg BID tozadenant, with dose modification to 60 mg BID tozadenant permitted.
All Cause Mortality
	Tozadenant
	Affected / at Risk (%)	# Events
Total	2/66 (3%)
Serious Adverse Events
	Tozadenant
	Affected / at Risk (%)	# Events
Total	5/66 (7.6%)
Blood and lymphatic system disorders
Agranulocytosis	2/66 (3%)
Gastrointestinal disorders
Colitis ischaemic	1/66 (1.5%)
Hepatobiliary disorders
Gallbladder disorder	1/66 (1.5%)
Infections and infestations
Abdominal abscess	1/66 (1.5%)
Atypical pneumonia	1/66 (1.5%)
Diverticulitis	1/66 (1.5%)
Septic shock	1/66 (1.5%)
Injury, poisoning and procedural complications
Tibia fracture	1/66 (1.5%)
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration	1/66 (1.5%)
Other (Not Including Serious) Adverse Events
	Tozadenant
	Affected / at Risk (%)	# Events
Total	46/66 (69.7%)
Blood and lymphatic system disorders
Agranulocytosis	2/66 (3%)
Gastrointestinal disorders
Nausea	6/66 (9.1%)
Diarrhea	3/66 (4.5%)
Abdominal pain	2/66 (3%)
Constipation	2/66 (3%)
Infections and infestations
Upper respiratory tract infection	4/66 (6.1%)
Nasopharyngitis	3/66 (4.5%)
Urinary tract infection	2/66 (3%)
Injury, poisoning and procedural complications
Fall	7/66 (10.6%)
Contusion	2/66 (3%)
Drug administration error	2/66 (3%)
Investigations
Blood creatinine increased	2/66 (3%)
Blood glucose increased	2/66 (3%)
Blood pressure increased	2/66 (3%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/66 (3%)
Joint Swelling	2/66 (3%)
Nervous system disorders
Dyskinesia	17/66 (25.8%)
Parkinson's Disease	3/66 (4.5%)
Headache	2/66 (3%)
Tremor	2/66 (3%)
Psychiatric disorders
Hallucination	3/66 (4.5%)
Anxiety	2/66 (3%)
Insomnia	2/66 (3%)
Respiratory, thoracic and mediastinal disorders
Cough	2/66 (3%)
Vascular disorders
Hypertension	2/66 (3%)
Orthostatic hypotension	2/66 (3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding the study results for a period up to 30 days from the date the communication is submitted to the sponsor. The sponsor shall have the right to defer proposed publication an additional 60 days from the end of the review period. The sponsor cannot require changes to the communication and cannot unilaterally extend the embargo.