Trial Outcomes & Findings for Safety and Efficacy of Liraglutide in Parkinson's Disease (NCT NCT02953665)

Last Updated: 2024-03-07

Results Overview

The UPDRS Part III (motor symptoms sub-scale) Assessment consists of 17 items, measured on a 5-Point scale (0-Normal to 4-Severe), addressing speech, facial expression, tremor at rest, action tremor, rigidity, finger taps, hand movements, hand pronation and supination, leg agility, arising from chair, posture, gait, postural stability, and body bradykinesia. The participant's score is calculated as a sum of the scores of the 17 individual questions. This sum score ranges from 0 to 108. Higher scores denote greater disability. A participant has been considered "OFF" when he/she has been off L-dopa for greater than 12 hours. During "OFF" time, the participant will not report feeling the effects of their anti-Parkinson's medication. The participant recorded the exact time of L-dopa intake. Assessment was only conducted greater than 12 hours after dosing with the participant reportedly feeling "OFF."

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

63 participants

Primary outcome timeframe

From Baseline (Week 0) to end of Maintenance Period (up to 54 weeks)

Results posted on

2024-03-07

Participant Flow

Participant milestones

Participant milestones
Measure	Liraglutide Liraglutide 6 mg/ml (Novo Nordisk A/S) will be self-administered subcutaneously once daily at a maximum dose of 1.8 mg after a 2 week titration schedule. Liraglutide: Liraglutide 6 mg/ml once daily at a maximum dose of 1.8 mg	Placebo Placebo will be self-administered subcutaneously once daily according to the same schedule. Placebo: Placebo (for Liraglutide) 6 mg/ml once daily at a maximum dose of 1.8 mg
Overall Study STARTED	42	21
Overall Study COMPLETED	33	18
Overall Study NOT COMPLETED	9	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Efficacy of Liraglutide in Parkinson's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Liraglutide n=42 Participants Liraglutide 6 mg/ml (Novo Nordisk A/S) will be self-administered subcutaneously once daily at a maximum dose of 1.8 mg after a 2 week titration schedule. Liraglutide: Liraglutide 6 mg/ml once daily at a maximum dose of 1.8 mg	Placebo n=21 Participants Placebo will be self-administered subcutaneously once daily according to the same schedule. Placebo: Placebo (for Liraglutide) 6 mg/ml once daily at a maximum dose of 1.8 mg	Total n=63 Participants Total of all reporting groups
Age, Customized 40-49 years of age	5 participants n=5 Participants	0 participants n=7 Participants	5 participants n=5 Participants
Age, Customized 50-59 years of age	5 participants n=5 Participants	8 participants n=7 Participants	13 participants n=5 Participants
Age, Customized 60-69 years of age	21 participants n=5 Participants	9 participants n=7 Participants	30 participants n=5 Participants
Age, Customized 70+ years of age	11 participants n=5 Participants	4 participants n=7 Participants	15 participants n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	6 Participants n=7 Participants	19 Participants n=5 Participants
Sex: Female, Male Male	29 Participants n=5 Participants	15 Participants n=7 Participants	44 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	40 Participants n=5 Participants	21 Participants n=7 Participants	61 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	42 Participants n=5 Participants	19 Participants n=7 Participants	61 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	42 participants n=5 Participants	21 participants n=7 Participants	63 participants n=5 Participants
Age of Onset	58.7 years STANDARD_DEVIATION 9.9 • n=5 Participants	58.5 years STANDARD_DEVIATION 7.4 • n=7 Participants	58.6 years STANDARD_DEVIATION 9.1 • n=5 Participants
Duration of Parkinson's Disease Symptoms	5.3 years STANDARD_DEVIATION 3.7 • n=5 Participants	4.9 years STANDARD_DEVIATION 3.2 • n=7 Participants	5.1 years STANDARD_DEVIATION 3.5 • n=5 Participants

PRIMARY outcome

Timeframe: From Baseline (Week 0) to end of Maintenance Period (up to 54 weeks)

Population: The Full Analysis Set (FAS) consisted of all subjects who were randomized, received at least 1 dose of study medication, had a valid Baseline primary efficacy measurement, and had at least 1 valid post-Baseline primary efficacy measurement.

Outcome measures

Outcome measures
Measure	Full Analysis Set (Liraglutide-treated Subjects) n=33 Participants Subjects receiving Liraglutide 6 mg/ml (Novo Nordisk A/S) self-administered subcutaneously once daily at a maximum dose of 1.8 mg after a 2-week titration schedule.	Full Analysis Set (Placebo-treated Subjects) n=18 Participants Subjects randomized to placebo self-administered matching placebo subcutaneously once daily according to the same schedule.
Change in Unified Parkinson's Disease Rating Scale (UPDRS Part III Motor Examination) During "OFF" Time From Baseline to the End of Double-Blind Maintenance Period	-2.3 units on a scale Standard Deviation 9.4	-5.0 units on a scale Standard Deviation 7.1

PRIMARY outcome

Timeframe: From Baseline (Week 0) to the End of Maintenance Period (up to Week 54)

The NMSS is a 30-item rater-based scale to assess a wide range of non-motor symptoms in patients with Parkinson's disease. The NMSS measures severity and frequency of non-motor symptoms across nine dimensions (cardiovascular, sleep/fatigue, mood/apathy, perceptual problems/hallucinations, attention/memory, gastrointestinal, urinary, sexual function, and miscellaneous which includes pain, taste/smell, weight change, and excessive sweating). Higher scores indicate a higher burden of these symptoms on the patient. There are 30 items to be scored, and the item scores are calculated as the product of severity and frequency; the total score is obtained by summing the item scores. The NMSS total score ranges from 0 to 360 with a lower score indicating fewer symptoms; a negative change from baseline indicates improvement in symptoms.

Outcome measures

Outcome measures
Measure	Full Analysis Set (Liraglutide-treated Subjects) n=33 Participants Subjects receiving Liraglutide 6 mg/ml (Novo Nordisk A/S) self-administered subcutaneously once daily at a maximum dose of 1.8 mg after a 2-week titration schedule.	Full Analysis Set (Placebo-treated Subjects) n=18 Participants Subjects randomized to placebo self-administered matching placebo subcutaneously once daily according to the same schedule.
Change in the Non-Motor Symptoms Scale (NMSS) Total Score From Baseline to the End of the Double-Blind Maintenance Period	-5.5 units on a scale Standard Deviation 25.3	6.5 units on a scale Standard Deviation 21.3

PRIMARY outcome

Timeframe: From Baseline (Week 0) to the end of Maintenance Period (up to 54 weeks)

The DRS-2 assesses individuals in five areas resulting in five sub-scale scores. These scores are used to determine the overall score and level of cognitive functioning ability. The five areas include: Attention - measured using eight items Construction - measured using six items Conceptualization - measured using six items Initiation/Preservation - measured using eleven items Memory - measured using five items Higher raw scores indicate better cognitive status, with scores ranging from 0 to 144. Normative data in healthy subjects range from 137 to 144.

Outcome measures

Outcome measures
Measure	Full Analysis Set (Liraglutide-treated Subjects) n=33 Participants Subjects receiving Liraglutide 6 mg/ml (Novo Nordisk A/S) self-administered subcutaneously once daily at a maximum dose of 1.8 mg after a 2-week titration schedule.	Full Analysis Set (Placebo-treated Subjects) n=18 Participants Subjects randomized to placebo self-administered matching placebo subcutaneously once daily according to the same schedule.
Change in the Mattis Dementia Rating Scale (DRS-2) From Baseline to the End of Double-Blind Maintenance Period	1.4 units on a scale Standard Deviation 9.3	-0.3 units on a scale Standard Deviation 9.1

SECONDARY outcome

Timeframe: From Baseline (Week 0) to end of Maintenance Period (up to 54 weeks)

Peripheral insulin resistance was assessed using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) Index. The HOMA-IR tool is a validated, non-invasive tool to assess the relationship between glucose and insulin. A score less than 1 means indicates insulin-sensitivity (Optimal). Greater than 1.9 indicates early insulin resistance, and a score greater than 2.9 indicates significant insulin resistance. An increase in one's HOMA-IR score may indicate increased insulin resistance.

Outcome measures

Outcome measures
Measure	Full Analysis Set (Liraglutide-treated Subjects) n=33 Participants Subjects receiving Liraglutide 6 mg/ml (Novo Nordisk A/S) self-administered subcutaneously once daily at a maximum dose of 1.8 mg after a 2-week titration schedule.	Full Analysis Set (Placebo-treated Subjects) n=18 Participants Subjects randomized to placebo self-administered matching placebo subcutaneously once daily according to the same schedule.
Change in the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) Index From Baseline to the End of Maintenance Period	0.1 units on a scale Standard Deviation 1.1	0.3 units on a scale Standard Deviation 0.8

SECONDARY outcome

Timeframe: From Baseline (Week 0) to end of Maintenance Period (up to 54 weeks)

Total UPDRS Score (Parts I, II, III, and IV; administered in the ON condition) Change from Baseline to End of Maintenance Period. UPDRS I evaluation of mentation, behavior, and mood UPDRS II self-evaluation of the activities of daily life (ADLs) including speech, swallowing, handwriting, dressing, hygiene, falling, salivating, turning in bed, walking, and cutting food UPDRS III clinician-scored monitored motor evaluation UPDRS IV evaluation of complications in therapy and motor fluctuations, including OFF time and dyskinesia The UPDRS I, II, III, and IV scores and subscores are calculated as the sum of all individual items. Subscales have 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe The final cumulative score will range from 0 (no disability) to 260 (total disability). A decrease in the mean indicates global improvement in the UPDRS score.

Outcome measures

Outcome measures
Measure	Full Analysis Set (Liraglutide-treated Subjects) n=33 Participants Subjects receiving Liraglutide 6 mg/ml (Novo Nordisk A/S) self-administered subcutaneously once daily at a maximum dose of 1.8 mg after a 2-week titration schedule.	Full Analysis Set (Placebo-treated Subjects) n=18 Participants Subjects randomized to placebo self-administered matching placebo subcutaneously once daily according to the same schedule.
Change in the Unified Parkinson's Disease Rating Scale Total Score From Baseline to the End of Double-Blind Maintenance Period	-4.9 units on a scale Standard Deviation 12.7	2.3 units on a scale Standard Deviation 10.4

SECONDARY outcome

Timeframe: From Baseline (Week 0) to end of Maintenance Period (up to 54 weeks)

The Parkinson's Disease Questionnaire (PDQ-39) is a 39-item patient-reported rating scale that measures Parkinson's disease-specific health related quality of life. It covers 8 areas: mobility, activities of daily living (ADL), emotional well-being, stigma, social support, cognition, communication and bodily discomfort. Lower scores indicate better health related quality of life. PDQ-39 total scores range from 0 to 800. The total score can be summarised into the PDQ-39 summary index score (range of scores 0 to 100). A mean change in the PDQ-39 summary index score of about 1.6 points relates to feeling 'a little worse' and is likely to represent a clinically important difference.

Outcome measures

Outcome measures
Measure	Full Analysis Set (Liraglutide-treated Subjects) n=33 Participants Subjects receiving Liraglutide 6 mg/ml (Novo Nordisk A/S) self-administered subcutaneously once daily at a maximum dose of 1.8 mg after a 2-week titration schedule.	Full Analysis Set (Placebo-treated Subjects) n=18 Participants Subjects randomized to placebo self-administered matching placebo subcutaneously once daily according to the same schedule.
Change in The Parkinson's Disease Questionnaire (PDQ-39) From Baseline to the End of Double-Blind Maintenance Period	-2.5 units on a scale Standard Deviation 9.9	11.2 units on a scale Standard Deviation 14.0

Adverse Events

Liraglutide

Serious events: 9 serious events

Other events: 42 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Liraglutide n=42 participants at risk Liraglutide 6 mg/ml (Novo Nordisk A/S) self-administered subcutaneously once daily at a maximum dose of 1.8 mg after a 2 week titration schedule. Liraglutide: Liraglutide 6 mg/ml once daily at a maximum dose of 1.8 mg	Placebo n=21 participants at risk Matching Placebo self-administered subcutaneously once daily according to the same schedule. Placebo: Placebo (for Liraglutide) 6 mg/ml once daily at a maximum dose of 1.8 mg
Injury, poisoning and procedural complications Fall/Admission for Fall	4.8% 2/42 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.	0.00% 0/21 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.
Renal and urinary disorders Urinary Tract Infection (UTI)/Admission for UTI	2.4% 1/42 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.	0.00% 0/21 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.
Nervous system disorders Dizziness/Admission for Dizziness	2.4% 1/42 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.	0.00% 0/21 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.
Vascular disorders Hospital Admission for Averted Stroke	0.00% 0/42 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.	4.8% 1/21 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.
Renal and urinary disorders Worsening Urinary Retention	2.4% 1/42 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.	0.00% 0/21 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.
Renal and urinary disorders Hospital Admission for Acute Kidney Injury	2.4% 1/42 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.	0.00% 0/21 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.
Renal and urinary disorders Prostate Cancer	2.4% 1/42 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.	4.8% 1/21 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.
Reproductive system and breast disorders Squamous Cell Carcinoma of Cervix	2.4% 1/42 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.	0.00% 0/21 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.
Reproductive system and breast disorders Invasive Lobular Carcinoma	2.4% 1/42 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.	0.00% 0/21 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.

Other adverse events

Additional Information

Vicki Manoukian, Neurology Clinical Research Program Manager

Cedars-Sinai

Phone: 310-423-5067

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Liraglutide n=42 participants at risk Liraglutide 6 mg/ml (Novo Nordisk A/S) self-administered subcutaneously once daily at a maximum dose of 1.8 mg after a 2 week titration schedule. Liraglutide: Liraglutide 6 mg/ml once daily at a maximum dose of 1.8 mg	Placebo n=21 participants at risk Matching Placebo self-administered subcutaneously once daily according to the same schedule. Placebo: Placebo (for Liraglutide) 6 mg/ml once daily at a maximum dose of 1.8 mg
Gastrointestinal disorders Nausea	57.1% 24/42 • Number of events 31 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.	14.3% 3/21 • Number of events 4 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.
Metabolism and nutrition disorders Loss of Appetite	61.9% 26/42 • Number of events 26 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.	0.00% 0/21 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.
Gastrointestinal disorders Dyspepsia	28.6% 12/42 • Number of events 16 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.	14.3% 3/21 • Number of events 3 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.
General disorders Injection Site Reaction	23.8% 10/42 • Number of events 10 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.	14.3% 3/21 • Number of events 4 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.
Musculoskeletal and connective tissue disorders Back Pain	11.9% 5/42 • Number of events 6 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.	14.3% 3/21 • Number of events 3 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.
Gastrointestinal disorders Diarrhea	14.3% 6/42 • Number of events 8 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.	9.5% 2/21 • Number of events 2 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.
Nervous system disorders Other Pain	16.7% 7/42 • Number of events 7 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.	4.8% 1/21 • Number of events 1 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.
Infections and infestations Upper Respiratory Tract Infection	9.5% 4/42 • Number of events 4 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.	14.3% 3/21 • Number of events 3 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.
Gastrointestinal disorders Constipation	14.3% 6/42 • Number of events 6 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.	0.00% 0/21 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.
General disorders Fatigue	9.5% 4/42 • Number of events 4 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.	4.8% 1/21 • Number of events 1 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.
Nervous system disorders Headache	7.1% 3/42 • Number of events 4 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.	9.5% 2/21 • Number of events 2 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.
Nervous system disorders Sleep Disorder	9.5% 4/42 • Number of events 4 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.	4.8% 1/21 • Number of events 1 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.
Renal and urinary disorders Urinary Tract Infection	7.1% 3/42 • Number of events 3 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.	9.5% 2/21 • Number of events 3 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.
Gastrointestinal disorders Vomiting	11.9% 5/42 • Number of events 6 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.	0.00% 0/21 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.
Nervous system disorders Worsening Off Time	7.1% 3/42 • Number of events 3 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.	9.5% 2/21 • Number of events 2 • Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.