Trial Outcomes & Findings for Phase II Subthalamic Nucleus (STN) vs. Globus Pallidus (GPi) Trial (NCT NCT01076452)

Last Updated: 2014-07-14

Results Overview

The primary outcome measure for the comparison of GPi deep brain stimulation (DBS) to STN DBS is the motor function score of the Unified Parkinson's Disease Rating Scale (UPDRS Part III) measured while the patient is off medications and on stimulation at follow-up visits post surgery. UPDRS Part III has 14 items assessing motor skills including facial expression and speech, tremors, rigidity, posture, gait, and bradykinesia. Left and right sides (arms, legs, and hands) are assessed separately for seven of the functions. The motor function (UPDRS part III) assessments are done by turning on the stimulation with and without taking PD medications (on/off) at each in-person visit. A summary score ranging from 0 to 108 is generated by adding the 14 specific motor function responses. The higher score indicates the worse motor function.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

299 participants

Primary outcome timeframe

Baseline and 24 months

Results posted on

2014-07-14

Participant Flow

299 subjects were enrolled into the study from May 2002 to September 2006 at 13 clinical sites including 7 VA Medical Centers and 6 affiliated university medical centers.

Participant milestones

Participant milestones
Measure	Arm 1 STN (Subthalamic Nucleus) Bilateral Deep Brain Stimulation : The DBS site (STN or GPi) will be assigned on a random basis at the time the patient enters the surgical phase of the trial.	Arm 2 GPi (Globus Pallidus) Bilateral Deep Brain Stimulation : The DBS site (STN or GPi) will be assigned on a random basis at the time the patient enters the surgical phase of the trial.
Overall Study STARTED	147	152
Overall Study COMPLETED	123	138
Overall Study NOT COMPLETED	24	14

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Phase II Subthalamic Nucleus (STN) vs. Globus Pallidus (GPi) Trial

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm 1 n=147 Participants STN (Subthalamic Nucleus) Bilateral Deep Brain Stimulation : The DBS site (STN or GPi) will be assigned on a random basis at the time the patient enters the surgical phase of the trial.	Arm 2 n=152 Participants GPi (Globus Pallidus) Bilateral Deep Brain Stimulation : The DBS site (STN or GPi) will be assigned on a random basis at the time the patient enters the surgical phase of the trial.	Total n=299 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	113 Participants n=5 Participants	117 Participants n=7 Participants	230 Participants n=5 Participants
Age, Categorical >=65 years	34 Participants n=5 Participants	35 Participants n=7 Participants	69 Participants n=5 Participants
Age, Continuous	61.9 years STANDARD_DEVIATION 8.7 • n=5 Participants	61.8 years STANDARD_DEVIATION 8.7 • n=7 Participants	61.8 years STANDARD_DEVIATION 8.6 • n=5 Participants
Sex: Female, Male Female	31 Participants n=5 Participants	19 Participants n=7 Participants	50 Participants n=5 Participants
Sex: Female, Male Male	116 Participants n=5 Participants	133 Participants n=7 Participants	249 Participants n=5 Participants
Region of Enrollment United States	147 participants n=5 Participants	152 participants n=7 Participants	299 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 24 months

Outcome measures

Outcome measures
Measure	STN (Subthalamic Nucleus) n=147 Participants STN (Subthalamic Nucleus) Bilateral Deep Brain Stimulation : The DBS site (STN or GPi) will be assigned on a random basis at the time the patient enters the surgical phase of the trial.	GPi (Globus Pallidus) n=152 Participants GPi (Globus Pallidus) Bilateral Deep Brain Stimulation : The DBS site (STN or GPi) will be assigned on a random basis at the time the patient enters the surgical phase of the trial.
The Change From Baseline in the UPDRS-III Score at 24 Months With Deep-brain Stimulation and Without Medication.	-12.9 units on a scale Interval -15.4 to -10.4	-13.1 units on a scale Interval -15.5 to -10.8

SECONDARY outcome

Timeframe: Baseline and 24 months

The UPDRS has four parts (Parts I-IV) in which a total of 42 disease characteristics are assessed. Most characteristics are assessed according to their severity on a 0-4 scale (0 = normal, 4 = most substantial impairment), and some are assessed only for absence (score = 0) or presence (score = 1). Part I has four items assessing intellectual impairment, thought disorder, depression and motivation. A summary score ranging from 0 to16 is generated by adding the four items. The higher score indicates worse condition.

Outcome measures

Outcome measures
Measure	STN (Subthalamic Nucleus) n=147 Participants STN (Subthalamic Nucleus) Bilateral Deep Brain Stimulation : The DBS site (STN or GPi) will be assigned on a random basis at the time the patient enters the surgical phase of the trial.	GPi (Globus Pallidus) n=152 Participants GPi (Globus Pallidus) Bilateral Deep Brain Stimulation : The DBS site (STN or GPi) will be assigned on a random basis at the time the patient enters the surgical phase of the trial.
The Change From Baseline in the UPDRS Scores Part I (Mentation) at 24 Months.	0.6 units on a scale Standard Deviation 2.2	0.4 units on a scale Standard Deviation 2.2

SECONDARY outcome

Timeframe: Baseline and 24 months

The UPDRS has four parts (Parts I-IV) in which a total of 42 disease characteristics are assessed. Most characteristics are assessed according to their severity on a 0-4 scale (0 = normal, 4 = most substantial impairment), and some are assessed only for absence (score = 0) or presence (score = 1). Part II has 13 items focusing on activities of daily living including walking, writing, dressing and speech. A summary score ranging from 0 to 52 is generated by adding the 13 items. The higher score indicates worse condition.

Outcome measures

Outcome measures
Measure	STN (Subthalamic Nucleus) n=147 Participants STN (Subthalamic Nucleus) Bilateral Deep Brain Stimulation : The DBS site (STN or GPi) will be assigned on a random basis at the time the patient enters the surgical phase of the trial.	GPi (Globus Pallidus) n=152 Participants GPi (Globus Pallidus) Bilateral Deep Brain Stimulation : The DBS site (STN or GPi) will be assigned on a random basis at the time the patient enters the surgical phase of the trial.
The Change From Baseline in the UPDRS Scores Part II (Activity of Daily Living) at 24 Months.	-2.3 units on a scale Standard Deviation 6.6	-3.4 units on a scale Standard Deviation 6.5

SECONDARY outcome

Timeframe: Baseline and 24 months

The UPDRS has four parts (Parts I-IV) in which a total of 42 disease characteristics are assessed. Most characteristics are assessed according to their severity on a 0-4 scale (0 = normal, 4 = most substantial impairment), and some are assessed only for absence (score = 0) or presence (score = 1). Part IV includes four categories (11 items) related to dyskinesias, clinical fluctuations of symptoms, and other complications. A summary score ranging from 0 to 23 is generated by adding the four items. The higher score indicates worse condition.

Outcome measures

Outcome measures
Measure	STN (Subthalamic Nucleus) n=147 Participants STN (Subthalamic Nucleus) Bilateral Deep Brain Stimulation : The DBS site (STN or GPi) will be assigned on a random basis at the time the patient enters the surgical phase of the trial.	GPi (Globus Pallidus) n=152 Participants GPi (Globus Pallidus) Bilateral Deep Brain Stimulation : The DBS site (STN or GPi) will be assigned on a random basis at the time the patient enters the surgical phase of the trial.
The Change From Baseline in the UPDRS Scores Part IV (Complication of Therapy) at 24 Months.	-3.9 units on a scale Standard Deviation 3.4	-3.4 units on a scale Standard Deviation 3.8

Adverse Events

Arm 1

Serious events: 83 serious events

Other events: 145 other events

Deaths: 0 deaths

Arm 2

Serious events: 77 serious events

Other events: 150 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Frances M. Weaver, Ph.D

Hines Veterans Affairs Hospital Center for Management of Complex Chronic Care

Phone: 708-202-8387

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Serious adverse events
Measure	Arm 1 n=147 participants at risk STN (Subthalamic Nucleus) Bilateral Deep Brain Stimulation : The DBS site (STN or GPi) will be assigned on a random basis at the time the patient enters the surgical phase of the trial.	Arm 2 n=152 participants at risk GPi (Globus Pallidus) Bilateral Deep Brain Stimulation : The DBS site (STN or GPi) will be assigned on a random basis at the time the patient enters the surgical phase of the trial.
Infections and infestations Implantation-site infection	7.5% 11/147 • Number of events 14 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	7.9% 12/152 • Number of events 17 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Injury, poisoning and procedural complications Fall	8.8% 13/147 • Number of events 16 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	3.3% 5/152 • Number of events 5 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Infections and infestations Pneumonia	2.7% 4/147 • Number of events 4 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	5.3% 8/152 • Number of events 8 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Psychiatric disorders Confusional state	3.4% 5/147 • Number of events 5 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	1.3% 2/152 • Number of events 2 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Injury, poisoning and procedural complications Medical device complication	2.7% 4/147 • Number of events 5 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	1.3% 2/152 • Number of events 2 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Musculoskeletal and connective tissue disorders Lumbar spine stenosis	1.4% 2/147 • Number of events 2 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	2.0% 3/152 • Number of events 4 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Psychiatric disorders Mental Status Change	0.68% 1/147 • Number of events 2 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	2.6% 4/152 • Number of events 4 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Musculoskeletal and connective tissue disorders Osteoarthritis	1.4% 2/147 • Number of events 2 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	2.0% 3/152 • Number of events 3 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Nervous system disorders Syncope	2.7% 4/147 • Number of events 4 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	0.66% 1/152 • Number of events 1 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Psychiatric disorders Depression	0.68% 1/147 • Number of events 1 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	2.6% 4/152 • Number of events 4 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
General disorders Adverse Drug Reaction	1.4% 2/147 • Number of events 2 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	1.3% 2/152 • Number of events 2 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Cardiac disorders Coronary Artery Disease	2.0% 3/147 • Number of events 3 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	0.66% 1/152 • Number of events 1 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Nervous system disorders Dyskinesia	2.0% 3/147 • Number of events 3 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	0.66% 1/152 • Number of events 1 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Gastrointestinal disorders Gastroesophageal reflux disease	1.4% 2/147 • Number of events 2 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	1.3% 2/152 • Number of events 2 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Gastrointestinal disorders Inguinal hernia	1.4% 2/147 • Number of events 2 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	1.3% 2/152 • Number of events 2 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Psychiatric disorders Suicidal Depression	0.68% 1/147 • Number of events 1 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	1.3% 2/152 • Number of events 2 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Psychiatric disorders Suicidal Ideation	0.68% 1/147 • Number of events 1 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	0.00% 0/152 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Psychiatric disorders Suicide Attempt	1.4% 2/147 • Number of events 2 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	0.00% 0/152 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Nervous system disorders Cerebral hemorrhage	1.4% 2/147 • Number of events 2 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	0.66% 1/152 • Number of events 1 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Nervous system disorders Stroke	2.0% 3/147 • Number of events 3 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	0.00% 0/152 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Nervous system disorders Intracranial Hemorrhage	0.00% 0/147 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	2.0% 3/152 • Number of events 3 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Blood and lymphatic system disorders Anaemia	0.68% 1/147 • Number of events 2 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	0.66% 1/152 • Number of events 1 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Cardiac disorders Cardiac Failure Congestive	1.4% 2/147 • Number of events 3 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	0.00% 0/152 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Cardiac disorders Myocardial infarction	0.68% 1/147 • Number of events 1 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	0.66% 1/152 • Number of events 2 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Cardiac disorders Angina Pectoris	0.00% 0/147 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	0.66% 1/152 • Number of events 1 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Gastrointestinal disorders gastrointestinal disorders	0.68% 1/147 • Number of events 1 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	0.00% 0/152 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
General disorders Chest Pain	1.4% 2/147 • Number of events 2 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	0.66% 1/152 • Number of events 1 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Immune system disorders drug hypersensitivity	1.4% 2/147 • Number of events 2 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	0.66% 1/152 • Number of events 1 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Infections and infestations Cellulitis	0.00% 0/147 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	0.66% 1/152 • Number of events 1 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Injury, poisoning and procedural complications Road Traffic accidents	2.0% 3/147 • Number of events 4 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	0.00% 0/152 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Cardiac disorders Angina Unstable	0.68% 1/147 • Number of events 1 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	0.00% 0/152 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Cardiac disorders Atrial Fibrillation	0.68% 1/147 • Number of events 1 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	0.66% 1/152 • Number of events 1 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Cardiac disorders Atrioventricular Block Complete	0.00% 0/147 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	0.66% 1/152 • Number of events 1 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Cardiac disorders Coronary Artery Occlusion	0.68% 1/147 • Number of events 1 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	0.00% 0/152 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Cardiac disorders Coronary Artery Restenosis	0.68% 1/147 • Number of events 1 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	0.00% 0/152 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Cardiac disorders Palpitations	0.00% 0/147 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	0.66% 1/152 • Number of events 1 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Cardiac disorders Sick Sinus Syndrome	0.68% 1/147 • Number of events 1 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	0.00% 0/152 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Gastrointestinal disorders Appendicitis Perforated	0.00% 0/147 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	0.66% 1/152 • Number of events 1 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Gastrointestinal disorders Constipation	0.68% 1/147 • Number of events 1 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	0.00% 0/152 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Gastrointestinal disorders Gastric Polyps	0.00% 0/147 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	0.66% 1/152 • Number of events 1 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.

Other adverse events
Measure	Arm 1 n=147 participants at risk STN (Subthalamic Nucleus) Bilateral Deep Brain Stimulation : The DBS site (STN or GPi) will be assigned on a random basis at the time the patient enters the surgical phase of the trial.	Arm 2 n=152 participants at risk GPi (Globus Pallidus) Bilateral Deep Brain Stimulation : The DBS site (STN or GPi) will be assigned on a random basis at the time the patient enters the surgical phase of the trial.
Injury, poisoning and procedural complications Fall	70.1% 103/147 • Number of events 198 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	65.8% 100/152 • Number of events 157 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Nervous system disorders Freezing Phenomenon	44.2% 65/147 • Number of events 93 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	52.6% 80/152 • Number of events 113 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Blood and lymphatic system disorders Aneamia	4.8% 7/147 • Number of events 7 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	5.9% 9/152 • Number of events 14 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Eye disorders Diplopia	4.8% 7/147 • Number of events 7 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	2.0% 3/152 • Number of events 3 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Eye disorders Visual Disturbance	4.8% 7/147 • Number of events 7 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	7.9% 12/152 • Number of events 12 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Gastrointestinal disorders Constipation	32.7% 48/147 • Number of events 58 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	36.8% 56/152 • Number of events 65 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Gastrointestinal disorders Dysphagia	44.9% 66/147 • Number of events 84 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	46.7% 71/152 • Number of events 85 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Gastrointestinal disorders Gastrooesophageal reflux disease	8.2% 12/147 • Number of events 15 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	6.6% 10/152 • Number of events 10 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Gastrointestinal disorders Nausea	19.0% 28/147 • Number of events 32 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	11.8% 18/152 • Number of events 19 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Gastrointestinal disorders Vomiting	4.1% 6/147 • Number of events 6 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	5.3% 8/152 • Number of events 8 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
General disorders adverse drug reaction	6.8% 10/147 • Number of events 12 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	4.6% 7/152 • Number of events 14 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
General disorders Asthenia	7.5% 11/147 • Number of events 13 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	3.3% 5/152 • Number of events 5 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
General disorders Chest Pain	7.5% 11/147 • Number of events 12 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	6.6% 10/152 • Number of events 10 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
General disorders Fatigue	17.7% 26/147 • Number of events 29 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	15.8% 24/152 • Number of events 31 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
General disorders Gait Disturbance	48.3% 71/147 • Number of events 94 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	46.1% 70/152 • Number of events 98 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
General disorders Oedema Peripheral	11.6% 17/147 • Number of events 18 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	8.6% 13/152 • Number of events 13 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
General disorders Pain	34.0% 50/147 • Number of events 75 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	28.3% 43/152 • Number of events 65 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Infections and infestations Implant sight infection	8.2% 12/147 • Number of events 15 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	8.6% 13/152 • Number of events 19 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Infections and infestations Pneumonia	4.8% 7/147 • Number of events 8 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	7.9% 12/152 • Number of events 12 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Infections and infestations Urinary Tract Infection	15.0% 22/147 • Number of events 28 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	10.5% 16/152 • Number of events 29 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Injury, poisoning and procedural complications Incision Site Pain	21.1% 31/147 • Number of events 33 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	19.7% 30/152 • Number of events 31 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Injury, poisoning and procedural complications Procedural Pain	15.0% 22/147 • Number of events 32 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	19.1% 29/152 • Number of events 41 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Investigations Blood Pressure increase	6.8% 10/147 • Number of events 12 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	6.6% 10/152 • Number of events 18 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Musculoskeletal and connective tissue disorders Arthralgia	15.6% 23/147 • Number of events 26 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	5.9% 9/152 • Number of events 10 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Musculoskeletal and connective tissue disorders Back Pain	15.0% 22/147 • Number of events 22 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	15.8% 24/152 • Number of events 25 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Musculoskeletal and connective tissue disorders Muscle rigidity	34.0% 50/147 • Number of events 74 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	27.0% 41/152 • Number of events 61 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Musculoskeletal and connective tissue disorders Muscle spasms	10.2% 15/147 • Number of events 16 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	3.9% 6/152 • Number of events 8 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	7.5% 11/147 • Number of events 12 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	9.9% 15/152 • Number of events 15 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Musculoskeletal and connective tissue disorders Musculoskeletal Stiffness	37.4% 55/147 • Number of events 78 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	31.6% 48/152 • Number of events 79 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Nervous system disorders Akinesia	20.4% 30/147 • Number of events 41 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	21.7% 33/152 • Number of events 49 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Nervous system disorders Balance disorder	42.9% 63/147 • Number of events 81 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	43.4% 66/152 • Number of events 86 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Nervous system disorders Bradykinesia	32.0% 47/147 • Number of events 69 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	37.5% 57/152 • Number of events 86 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Nervous system disorders Drooling	38.1% 56/147 • Number of events 68 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	33.6% 51/152 • Number of events 54 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Nervous system disorders Dyskinesia	51.7% 76/147 • Number of events 116 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	40.8% 62/152 • Number of events 86 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Nervous system disorders Dystonia	40.8% 60/147 • Number of events 85 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	44.7% 68/152 • Number of events 89 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Nervous system disorders Headache	41.5% 61/147 • Number of events 72 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	40.1% 61/152 • Number of events 71 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Nervous system disorders memory Impairment	8.8% 13/147 • Number of events 14 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	15.1% 23/152 • Number of events 24 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Nervous system disorders Motor Dysfunction	35.4% 52/147 • Number of events 70 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	37.5% 57/152 • Number of events 84 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Nervous system disorders Poor Quality Sleep	6.1% 9/147 • Number of events 11 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	7.2% 11/152 • Number of events 12 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
Nervous system disorders Somnolence	12.2% 18/147 • Number of events 19 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.	11.8% 18/152 • Number of events 20 • 24 months Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.