Trial Outcomes & Findings for GM1 Ganglioside Effects on Parkinson's Disease (NCT NCT00037830)

Last Updated: 2012-12-21

Results Overview

The Unified Parkinson's Disease Rating Scale (UPDRS) (Part III) motor scores assess 14 symptoms some of which separately assess symptoms in different body parts (e.g. right arm, left arm, right leg, left leg) and each symptom is rated on a scale from 0 (normal) to 4 (severe). The minimum total score possible is 0 and the maximum total score possible is 108. Each subject was independently rated by two observers at each study visit and a mean score was calculated for analysis.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

94 participants

Primary outcome timeframe

Baseline to Week 24

Results posted on

2012-12-21

Participant Flow

Seventy-seven PD patients were recruited from all across the US for this single center, double-blind, delayed start trial of GM1. Seventeen subjects participated in the comparison group. Enrollment for the study began Nov 1999 and was completed in Jan 2006. Subjects were seen at the Parkinson's Disease Research Unit at Thomas Jefferson University.

Participant milestones

Participant milestones
Measure	Early-Start Group Phase I: Thirty nine subjects were randomized to receive GM1 for 24 weeks.	Delayed-Start Group Phase I: Thiry eight subjects were randomized to receive placebo for 24 weeks.	Comparison Group This group of PD patients who received standard of care were followed for one to two years to provide comparative information about natural disease progression. This group was not statistically compared to the treatment groups since this group was not randomized.
Overall Study STARTED	39	38	17
Overall Study COMPLETED	29	31	16
Overall Study NOT COMPLETED	10	7	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Early-Start Group Phase I: Thirty nine subjects were randomized to receive GM1 for 24 weeks.	Delayed-Start Group Phase I: Thiry eight subjects were randomized to receive placebo for 24 weeks.	Comparison Group This group of PD patients who received standard of care were followed for one to two years to provide comparative information about natural disease progression. This group was not statistically compared to the treatment groups since this group was not randomized.
Overall Study Adverse Event	2	0	0
Overall Study Withdrawal by Subject	4	5	1
Overall Study Protocol Violation	2	2	0
Overall Study Unrelated Medical Problem	2	0	0

Baseline Characteristics

GM1 Ganglioside Effects on Parkinson's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Early-Start Group n=39 Participants Phase I: Thirty nine subjects were randomized to receive GM1 for 24 weeks.	Delayed-Start Group n=38 Participants Phase I: Thiry eight subjects were randomized to receive placebo for 24 weeks.	Comparison Group n=17 Participants This group of PD patients who received standard of care were followed for one to two years to provide comparative information about natural disease progression. This group was not statistically compared to the treatment groups since this group was not randomized.	Total n=94 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	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	27 Participants n=5 Participants	29 Participants n=7 Participants	9 Participants n=5 Participants	65 Participants n=4 Participants
Age, Categorical >=65 years	12 Participants n=5 Participants	9 Participants n=7 Participants	8 Participants n=5 Participants	29 Participants n=4 Participants
Age Continuous	59.7 years STANDARD_DEVIATION 8.4 • n=5 Participants	57.7 years STANDARD_DEVIATION 8.7 • n=7 Participants	61.1 years STANDARD_DEVIATION 11.8 • n=5 Participants	59.5 years STANDARD_DEVIATION 9.6 • n=4 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	9 Participants n=7 Participants	3 Participants n=5 Participants	22 Participants n=4 Participants
Sex: Female, Male Male	29 Participants n=5 Participants	29 Participants n=7 Participants	14 Participants n=5 Participants	72 Participants n=4 Participants
Region of Enrollment United States	39 participants n=5 Participants	38 participants n=7 Participants	17 participants n=5 Participants	94 participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline to Week 24

Population: Analysis was per protocol. Two subjects randomized to the Early-Start group withdrew from the study shortly after starting. The comparison group was not compared statistically to the treatment group since they were not randomized.

Outcome measures

Outcome measures
Measure	Early-Start Group n=37 Participants Group that was randomized to receive GM1 ganglioside 24 weeks	Delayed-Start Group n=38 Participants Group that was randomized to receive placebo for 24 weeks
Change in Unified Parkinson's Disease Rating Scale (UPDRS) (Part III) Motor Score From Baseline to Week 24 Assessed Off Medication.	-3.57 Scores on a scale Standard Error .503	1.85 Scores on a scale Standard Error .497

PRIMARY outcome

Timeframe: Baseline to Week 120

Outcome measures

Outcome measures
Measure	Early-Start Group n=37 Participants Group that was randomized to receive GM1 ganglioside 24 weeks	Delayed-Start Group n=38 Participants Group that was randomized to receive placebo for 24 weeks
Change in Unified Parkinson's Disease Rating Scale (UPDRS) (Part III) Motor Scores From Baseline to Week 120 Assessed Off Medication.	-1.80 Scores on a scale Standard Error 1.117	1.53 Scores on a scale Standard Error 1.092

SECONDARY outcome

Timeframe: Baseline to Week 24

The total Unified Parkinson's Disease Rating Scale (UPDRS) score is derived from Part I (Mentation, Behavior and Mood), Part II (Activities of Daily Living) and Part III (Motor Examination). Part I assesses 4 functions; Part II assesses 13 activities of daily living; Part III assesses 14 motor symptoms. Each item is rated on a scale from 0 (normal) to 4 (severe). The minimum total score possible is 0 and the maximum total score possible is 176. Each subject was independently rated by two observers at each study visit and a mean score was calculated for analysis.

Outcome measures

Outcome measures
Measure	Early-Start Group n=37 Participants Group that was randomized to receive GM1 ganglioside 24 weeks	Delayed-Start Group n=38 Participants Group that was randomized to receive placebo for 24 weeks
Change From Baseline to Week 24 in Total Unified Parkinson's Disease Rating Scale (UPDRS)Score Assessed Off Medication	-5.31 Scores on a scale Standard Error 0.84	1.88 Scores on a scale Standard Error 0.83

SECONDARY outcome

Timeframe: Baseline to Week 120

Outcome measures

Outcome measures
Measure	Early-Start Group n=37 Participants Group that was randomized to receive GM1 ganglioside 24 weeks	Delayed-Start Group n=38 Participants Group that was randomized to receive placebo for 24 weeks
Change in Total UPDRS Score From Baseline to Week 120 Assessed Off Medication	-1.01 Scores on a scale Standard Error 1.764	3.56 Scores on a scale Standard Error 1.726

SECONDARY outcome

Timeframe: Baseline to Week 24

Outcome measures

Outcome measures
Measure	Early-Start Group n=17 Participants Group that was randomized to receive GM1 ganglioside 24 weeks	Delayed-Start Group Group that was randomized to receive placebo for 24 weeks
Change in Unified Parkinson's Disease Rating Scale (UPDRS) (Part III) Motor Score From Baseline to Week 24 Assessed Off Medication.	2.28 Scores on a scale Standard Error 0.866	—

SECONDARY outcome

Timeframe: Baseline to Week 48

Outcome measures

Outcome measures
Measure	Early-Start Group n=16 Participants Group that was randomized to receive GM1 ganglioside 24 weeks	Delayed-Start Group Group that was randomized to receive placebo for 24 weeks
Change in Unified Parkinson's Disease Rating Scale (UPDRS) (Part III) Motor Score From Baseline to Week 48 Assessed Off Medication.	4.41 Scores on a scale Standard Error 1.434	—

SECONDARY outcome

Timeframe: Baseline to Week 72

Population: Number of subjects enrolled at this time point.

Outcome measures

Outcome measures
Measure	Early-Start Group n=10 Participants Group that was randomized to receive GM1 ganglioside 24 weeks	Delayed-Start Group Group that was randomized to receive placebo for 24 weeks
Change in Unified Parkinson's Disease Rating Scale (UPDRS) (Part III) Motor Score From Baseline to Week 72 Assessed Off Medication.	5.95 Scores on a scale Standard Error 1.220	—

SECONDARY outcome

Timeframe: Baseline to Week 96

Population: Number of subjects enrolled at this time point.

Outcome measures

Outcome measures
Measure	Early-Start Group n=8 Participants Group that was randomized to receive GM1 ganglioside 24 weeks	Delayed-Start Group Group that was randomized to receive placebo for 24 weeks
Change in Unified Parkinson's Disease Rating Scale (UPDRS) (Part III) Motor Score From Baseline to Week 96 Assessed Off Medication.	7.81 Scores on scale Standard Error 2.014	—

POST_HOC outcome

Timeframe: Week 6 to Week 24

Unified Parkinson's Disease Rating Scale (UPDRS) A four part scale used to assess the severity of Parkinson's disease symptoms. Part I contains questions concerning the patient's mentation, behavior and mood. Part II asks questions about the patient's ability to perform activities of daily living. Part III is the motor examination of the patient's symptoms ranging in scores from 0 to 4 with 0 equaling either normal or absence of symptoms. The minimum score on this section is 0 and the maximum is 108. Part IV asks the patient questions about any complications of therapy they have experienced within the past week. However, for this study the total UPDRS included Parts I, II, and III. A higher the score on the scale indicates more severe symptoms.

Outcome measures

Outcome measures
Measure	Early-Start Group n=37 Participants Group that was randomized to receive GM1 ganglioside 24 weeks	Delayed-Start Group n=38 Participants Group that was randomized to receive placebo for 24 weeks
Estimated Change in Points Per Week on Unified Parkinson's Disease Rating Scale (UPDRS) Motor Score Assessed Off Medication	0.04 Scores on a scale Standard Error 0.03	0.08 Scores on a scale Standard Error 0.03

POST_HOC outcome

Timeframe: Week 36 to Week 120

Outcome measures

Outcome measures
Measure	Early-Start Group n=37 Participants Group that was randomized to receive GM1 ganglioside 24 weeks	Delayed-Start Group n=38 Participants Group that was randomized to receive placebo for 24 weeks
Estimated Rate of Change in Unified Parkinson's Disease Rating Scale (UPDRS)Motor Scores Assessed Off Medication	0.02 Scores on a scale Standard Error 0.01	0.04 Scores on a scale Standard Error 0.01

Adverse Events

Early-Start Group

Serious events: 2 serious events

Other events: 39 other events

Deaths: 0 deaths

Delayed-Start Group

Serious events: 1 serious events

Other events: 38 other events

Deaths: 0 deaths

Comparison Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Early-Start Group n=39 participants at risk Phase I: Thirty nine subjects were randomized to receive GM1 for 24 weeks.	Delayed-Start Group n=38 participants at risk Phase I: Thiry eight subjects were randomized to receive placebo for 24 weeks.	Comparison Group n=17 participants at risk This group of PD patients who received standard of care were followed for one to two years to provide comparative information about natural disease progression. This group was not statistically compared to the treatment groups since this group was not randomized.
General disorders Severe weakness L>R BLC LE's	2.6% 1/39 • Number of events 1 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/38 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
Injury, poisoning and procedural complications CT Scan showed an Ulcerating Mass Fungating in Stomach	2.6% 1/39 • Number of events 1 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/38 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/39 • Adverse events were collected for 2 and a half years beginning at baseline.	2.6% 1/38 • Number of events 1 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
Musculoskeletal and connective tissue disorders Muscle pain	0.00% 0/39 • Adverse events were collected for 2 and a half years beginning at baseline.	2.6% 1/38 • Number of events 1 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
Nervous system disorders Increase frequency of dyskinesias	0.00% 0/39 • Adverse events were collected for 2 and a half years beginning at baseline.	2.6% 1/38 • Number of events 1 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
Nervous system disorders Uncontrollable shaking	0.00% 0/39 • Adverse events were collected for 2 and a half years beginning at baseline.	2.6% 1/38 • Number of events 1 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
Surgical and medical procedures Laproscopic Removal of Stomal Tumor in Stomach	2.6% 1/39 • Number of events 1 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/38 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.

Other adverse events

Additional Information

Dr. Jay Schneider

Thomas Jefferson University

Phone: 215-503-0370

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Early-Start Group n=39 participants at risk Phase I: Thirty nine subjects were randomized to receive GM1 for 24 weeks.	Delayed-Start Group n=38 participants at risk Phase I: Thiry eight subjects were randomized to receive placebo for 24 weeks.	Comparison Group n=17 participants at risk This group of PD patients who received standard of care were followed for one to two years to provide comparative information about natural disease progression. This group was not statistically compared to the treatment groups since this group was not randomized.
Gastrointestinal disorders Nausea	10.3% 4/39 • Number of events 4 • Adverse events were collected for 2 and a half years beginning at baseline.	2.6% 1/38 • Number of events 1 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
Gastrointestinal disorders Diarrhoea	5.1% 2/39 • Number of events 2 • Adverse events were collected for 2 and a half years beginning at baseline.	2.6% 1/38 • Number of events 1 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
Gastrointestinal disorders Vomiting	5.1% 2/39 • Number of events 2 • Adverse events were collected for 2 and a half years beginning at baseline.	2.6% 1/38 • Number of events 1 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
Gastrointestinal disorders Abdominal pain	0.00% 0/39 • Adverse events were collected for 2 and a half years beginning at baseline.	5.3% 2/38 • Number of events 2 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
Gastrointestinal disorders Dry mouth	0.00% 0/39 • Adverse events were collected for 2 and a half years beginning at baseline.	5.3% 2/38 • Number of events 2 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
General disorders Injection site pain	51.3% 20/39 • Number of events 20 • Adverse events were collected for 2 and a half years beginning at baseline.	84.2% 32/38 • Number of events 32 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
General disorders Injection site erythema	5.1% 2/39 • Number of events 2 • Adverse events were collected for 2 and a half years beginning at baseline.	2.6% 1/38 • Number of events 1 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
General disorders Injection site nodule	28.2% 11/39 • Number of events 11 • Adverse events were collected for 2 and a half years beginning at baseline.	44.7% 17/38 • Number of events 17 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
General disorders Injection site haemorrhage	20.5% 8/39 • Number of events 8 • Adverse events were collected for 2 and a half years beginning at baseline.	31.6% 12/38 • Number of events 12 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
General disorders Injection site haematoma	23.1% 9/39 • Number of events 9 • Adverse events were collected for 2 and a half years beginning at baseline.	21.1% 8/38 • Number of events 8 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
General disorders Injection site pruritus	28.2% 11/39 • Number of events 11 • Adverse events were collected for 2 and a half years beginning at baseline.	15.8% 6/38 • Number of events 6 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
General disorders Injection site swelling	7.7% 3/39 • Number of events 3 • Adverse events were collected for 2 and a half years beginning at baseline.	13.2% 5/38 • Number of events 5 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
General disorders Injection site urticaria	12.8% 5/39 • Number of events 5 • Adverse events were collected for 2 and a half years beginning at baseline.	7.9% 3/38 • Number of events 3 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
General disorders Fatigue	7.7% 3/39 • Number of events 3 • Adverse events were collected for 2 and a half years beginning at baseline.	10.5% 4/38 • Number of events 4 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
General disorders Oedema peripheral	7.7% 3/39 • Number of events 3 • Adverse events were collected for 2 and a half years beginning at baseline.	7.9% 3/38 • Number of events 3 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
General disorders Injection site induration	5.1% 2/39 • Number of events 2 • Adverse events were collected for 2 and a half years beginning at baseline.	5.3% 2/38 • Number of events 2 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
General disorders Oedema	5.1% 2/39 • Number of events 2 • Adverse events were collected for 2 and a half years beginning at baseline.	5.3% 2/38 • Number of events 2 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
General disorders Gait disturbance	2.6% 1/39 • Number of events 1 • Adverse events were collected for 2 and a half years beginning at baseline.	5.3% 2/38 • Number of events 2 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
General disorders Feeling abnormal	5.1% 2/39 • Number of events 2 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/38 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
General disorders Injection site exfoliation	5.1% 2/39 • Number of events 2 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/38 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
Injury, poisoning and procedural complications Fall	2.6% 1/39 • Number of events 1 • Adverse events were collected for 2 and a half years beginning at baseline.	5.3% 2/38 • Number of events 2 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
Investigations Blood cholesterol increased	17.9% 7/39 • Number of events 7 • Adverse events were collected for 2 and a half years beginning at baseline.	10.5% 4/38 • Number of events 4 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
Investigations Blood triglycerides increased	15.4% 6/39 • Number of events 6 • Adverse events were collected for 2 and a half years beginning at baseline.	13.2% 5/38 • Number of events 5 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
Investigations Eosinophil count increased	7.7% 3/39 • Number of events 3 • Adverse events were collected for 2 and a half years beginning at baseline.	7.9% 3/38 • Number of events 3 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
Investigations Blood pressure increased	2.6% 1/39 • Number of events 1 • Adverse events were collected for 2 and a half years beginning at baseline.	5.3% 2/38 • Number of events 2 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
Investigations Crystal urine present	2.6% 1/39 • Number of events 1 • Adverse events were collected for 2 and a half years beginning at baseline.	5.3% 2/38 • Number of events 2 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
Investigations Alkaline amniotransferase increased	5.1% 2/39 • Number of events 2 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/38 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
Investigations Aspartate amnotransferase increased	5.1% 2/39 • Number of events 2 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/38 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
Musculoskeletal and connective tissue disorders Muscle spasms	7.7% 3/39 • Number of events 3 • Adverse events were collected for 2 and a half years beginning at baseline.	5.3% 2/38 • Number of events 2 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
Musculoskeletal and connective tissue disorders Pain in extremity	5.1% 2/39 • Number of events 2 • Adverse events were collected for 2 and a half years beginning at baseline.	10.5% 4/38 • Number of events 4 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
Musculoskeletal and connective tissue disorders Arthralgia	5.1% 2/39 • Number of events 2 • Adverse events were collected for 2 and a half years beginning at baseline.	2.6% 1/38 • Number of events 1 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
Nervous system disorders Parkinsonism	23.1% 9/39 • Number of events 9 • Adverse events were collected for 2 and a half years beginning at baseline.	13.2% 5/38 • Number of events 5 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
Nervous system disorders Tremor	12.8% 5/39 • Number of events 5 • Adverse events were collected for 2 and a half years beginning at baseline.	13.2% 5/38 • Number of events 5 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
Nervous system disorders Dizziness	7.7% 3/39 • Number of events 3 • Adverse events were collected for 2 and a half years beginning at baseline.	10.5% 4/38 • Number of events 4 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
Nervous system disorders Dyskinesia	5.1% 2/39 • Number of events 2 • Adverse events were collected for 2 and a half years beginning at baseline.	10.5% 4/38 • Number of events 4 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
Nervous system disorders Paresthesia	5.1% 2/39 • Number of events 2 • Adverse events were collected for 2 and a half years beginning at baseline.	7.9% 3/38 • Number of events 3 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
Nervous system disorders Balance disorder	2.6% 1/39 • Number of events 1 • Adverse events were collected for 2 and a half years beginning at baseline.	5.3% 2/38 • Number of events 2 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
Nervous system disorders Freezing phenomenon	2.6% 1/39 • Number of events 1 • Adverse events were collected for 2 and a half years beginning at baseline.	5.3% 2/38 • Number of events 2 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
Nervous system disorders Headache	5.1% 2/39 • Number of events 2 • Adverse events were collected for 2 and a half years beginning at baseline.	2.6% 1/38 • Number of events 1 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
Nervous system disorders Hypoaesthesia	0.00% 0/39 • Adverse events were collected for 2 and a half years beginning at baseline.	5.3% 2/38 • Number of events 2 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
Psychiatric disorders Insomnia	10.3% 4/39 • Number of events 4 • Adverse events were collected for 2 and a half years beginning at baseline.	7.9% 3/38 • Number of events 3 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
Psychiatric disorders Depression	5.1% 2/39 • Number of events 2 • Adverse events were collected for 2 and a half years beginning at baseline.	2.6% 1/38 • Number of events 1 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
Psychiatric disorders Anxiety	5.1% 2/39 • Number of events 2 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/38 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
Psychiatric disorders Vivid dreams	2.6% 1/39 • Number of events 1 • Adverse events were collected for 2 and a half years beginning at baseline.	7.9% 3/38 • Number of events 3 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
Skin and subcutaneous tissue disorders Rash	5.1% 2/39 • Number of events 2 • Adverse events were collected for 2 and a half years beginning at baseline.	2.6% 1/38 • Number of events 1 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.
Skin and subcutaneous tissue disorders Skin exfoliation	5.1% 2/39 • Number of events 2 • Adverse events were collected for 2 and a half years beginning at baseline.	2.6% 1/38 • Number of events 1 • Adverse events were collected for 2 and a half years beginning at baseline.	0.00% 0/17 • Adverse events were collected for 2 and a half years beginning at baseline.