Trial Outcomes & Findings for A Study Comparing Efficacy of Levodopa-Carbidopa Intestinal Gel/Carbidopa-Levodopa Enteral Suspension and Optimized Medical Treatment on Dyskinesia in Subjects With Advanced Parkinson's Disease (DYSCOVER) (NCT NCT02799381)

Last Updated: 2020-08-18

Results Overview

The Unified Dyskinesia Rating Scale (UDysRS) is a tool used to assess dyskinesia in Parkinson's disease (PD) and contains both self-evaluation questions and items that are assessed directly by the physician to objectively rate the abnormal movements associated with PD. Part 1 contains 11 questions about the ON time dyskinesia and the impact of ON-dyskinesia on experiences of daily living. Part 2 contains 4 questions about OFF-dystonia rating. Part 3 contains 7 questions about objective evaluation of dyskinesia impairment and Part 4 contains 4 questions regarding dyskinesia disability. Each question is scored with respect to severity, which is rated on a scale where 0 = normal, 1 = slight, 2 = mild, 3= moderate and 4 = severe. The UDysRS total score is obtained by summing the item scores, ranging from 0 to 104. Higher scores are associated with more disability. Negative changes from baseline indicate improvement.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

63 participants

Primary outcome timeframe

Baseline, Week 12

Results posted on

2020-08-18

Participant Flow

Safety Data Set: all participants randomized to OMT and all participants randomized to LCIG treatment who had a study tube (NJ or PEG-J) placement procedure. Two participants randomized to the LCIG arm did not have device placement for LCIG infusion and were not included in the safety data set.

Participant milestones

Participant milestones
Measure	Optimized Medical Treatment (OMT) Participants randomized to OMT continued their current anti Parkinson's disease (anti-PD) medication regimen for the duration of the study. All anti-PD medications and medications to treat dyskinesia must have remained stable for the duration of the study unless adjustments were medically indicated. The Investigator provided the prescription for continued OMT.	Levodopa-Carbidopa Intestinal Gel (LCIG) The total daily dose of infusion LCIG was composed of three components: (i) the morning dose, (ii) continuous maintenance infusion dose and (iii) extra doses. A temporary nasojejunal (NJ) tube may have been used initially with the infusion pump to determine a participant's response to this method of treatment and to optimize the dose of LCIG before treatment with a permanent percutaneous endoscopic gastrostomy - with jejunal extension (PEG-J) tube was started. Following optional NJ and/or PEG-J placement and, at the investigator's discretion, the participant may have begun initiation and titration of LCIG infusion on Day 1 once tube placement was confirmed. The dose of LCIG was adjusted to obtain the optimal clinical response. The rate of LCIG infusion is typically within the range of 1 to 10 mL/hour (20 to 200 mg of levodopa/hour) in most instances and runs over a period of 16 consecutive hours each day.
Overall Study STARTED	33	28
Overall Study COMPLETED	29	25
Overall Study NOT COMPLETED	4	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Optimized Medical Treatment (OMT) Participants randomized to OMT continued their current anti Parkinson's disease (anti-PD) medication regimen for the duration of the study. All anti-PD medications and medications to treat dyskinesia must have remained stable for the duration of the study unless adjustments were medically indicated. The Investigator provided the prescription for continued OMT.	Levodopa-Carbidopa Intestinal Gel (LCIG) The total daily dose of infusion LCIG was composed of three components: (i) the morning dose, (ii) continuous maintenance infusion dose and (iii) extra doses. A temporary nasojejunal (NJ) tube may have been used initially with the infusion pump to determine a participant's response to this method of treatment and to optimize the dose of LCIG before treatment with a permanent percutaneous endoscopic gastrostomy - with jejunal extension (PEG-J) tube was started. Following optional NJ and/or PEG-J placement and, at the investigator's discretion, the participant may have begun initiation and titration of LCIG infusion on Day 1 once tube placement was confirmed. The dose of LCIG was adjusted to obtain the optimal clinical response. The rate of LCIG infusion is typically within the range of 1 to 10 mL/hour (20 to 200 mg of levodopa/hour) in most instances and runs over a period of 16 consecutive hours each day.
Overall Study Withdrew consent	3	2
Overall Study Adverse Event	0	1
Overall Study Participant did not take any study drug	1	0

Baseline Characteristics

A Study Comparing Efficacy of Levodopa-Carbidopa Intestinal Gel/Carbidopa-Levodopa Enteral Suspension and Optimized Medical Treatment on Dyskinesia in Subjects With Advanced Parkinson's Disease (DYSCOVER)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Optimized Medical Treatment (OMT) n=33 Participants Participants randomized to OMT continued their current anti Parkinson's disease (anti-PD) medication regimen for the duration of the study. All anti-PD medications and medications to treat dyskinesia must have remained stable for the duration of the study unless adjustments were medically indicated. The Investigator provided the prescription for continued OMT.	Levodopa-Carbidopa Intestinal Gel (LCIG) n=28 Participants The total daily dose of infusion LCIG was composed of three components: (i) the morning dose, (ii) continuous maintenance infusion dose and (iii) extra doses. A temporary nasojejunal (NJ) tube may have been used initially with the infusion pump to determine a participant's response to this method of treatment and to optimize the dose of LCIG before treatment with a permanent percutaneous endoscopic gastrostomy - with jejunal extension (PEG-J) tube was started. Following optional NJ and/or PEG-J placement and, at the investigator's discretion, the participant may have begun initiation and titration of LCIG infusion on Day 1 once tube placement was confirmed. The dose of LCIG was adjusted to obtain the optimal clinical response. The rate of LCIG infusion is typically within the range of 1 to 10 mL/hour (20 to 200 mg of levodopa/hour) in most instances and runs over a period of 16 consecutive hours each day.	Total n=61 Participants Total of all reporting groups
Age, Continuous	68.7 years STANDARD_DEVIATION 7.20 • n=93 Participants	69.3 years STANDARD_DEVIATION 6.99 • n=4 Participants	69.0 years STANDARD_DEVIATION 7.05 • n=27 Participants
Sex: Female, Male Female	16 Participants n=93 Participants	16 Participants n=4 Participants	32 Participants n=27 Participants
Sex: Female, Male Male	17 Participants n=93 Participants	12 Participants n=4 Participants	29 Participants n=27 Participants
Race/Ethnicity, Customized White	33 Participants n=93 Participants	28 Participants n=4 Participants	61 Participants n=27 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race/Ethnicity, Customized Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race/Ethnicity, Customized Missing	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Body Mass Index (BMI)	25.2 kg/m^2 STANDARD_DEVIATION 4.42 • n=93 Participants	24.5 kg/m^2 STANDARD_DEVIATION 4.24 • n=4 Participants	24.9 kg/m^2 STANDARD_DEVIATION 4.32 • n=27 Participants
Parkinson's disease duration (years) < 10 years	14 Participants n=93 Participants	7 Participants n=4 Participants	21 Participants n=27 Participants
Parkinson's disease duration (years) ≥ 10 years	19 Participants n=93 Participants	20 Participants n=4 Participants	39 Participants n=27 Participants
Parkinson's disease duration (years) Missing	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: Intent-to-treat (ITT) population: all participants with available data who were randomized to the OMT and all participants who were randomized to LCIG treatment and received at least 1 dose of study drug following PEG-J placement

Outcome measures

Outcome measures
Measure	Optimized Medical Treatment (OMT) n=26 Participants Participants randomized to OMT continued their current anti Parkinson's disease (anti-PD) medication regimen for the duration of the study. All anti-PD medications and medications to treat dyskinesia must have remained stable for the duration of the study unless adjustments were medically indicated. The Investigator provided the prescription for continued OMT.	Levodopa-Carbidopa Intestinal Gel (LCIG) n=24 Participants The total daily dose of infusion LCIG was composed of three components: (i) the morning dose, (ii) continuous maintenance infusion dose and (iii) extra doses. A temporary nasojejunal (NJ) tube may have been used initially with the infusion pump to determine a participant's response to this method of treatment and to optimize the dose of LCIG before treatment with a permanent percutaneous endoscopic gastrostomy - with jejunal extension (PEG-J) tube was started. Following optional NJ and/or PEG-J placement and, at the investigator's discretion, the participant may have begun initiation and titration of LCIG infusion on Day 1 once tube placement was confirmed. The dose of LCIG was adjusted to obtain the optimal clinical response. The rate of LCIG infusion is typically within the range of 1 to 10 mL/hour (20 to 200 mg of levodopa/hour) in most instances and runs over a period of 16 consecutive hours each day.
Mean Change From Baseline to Week 12 in Unified Dyskinesia Rating Scale (UDysRS) Total Score	-2.33 units on a scale Standard Error 2.56	-17.37 units on a scale Standard Error 2.79

SECONDARY outcome

Timeframe: Baseline, Week 12

The Parkinson's Disease (PD) Symptom Diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected study visits. It reflects both time awake and time asleep. Daily totals are normalized to a 16-hour scale (i.e., 16 hours of awake time). The normalized totals for the 3 days prior to the visit are averaged for the analysis. ON time is when PD symptoms are well controlled by the drug, and OFF time is when PD symptoms are not adequately controlled by the drug. Positive change from baseline for ON time without troublesome dyskinesia indicates improvement.

Outcome measures

Outcome measures
Measure	Optimized Medical Treatment (OMT) n=28 Participants Participants randomized to OMT continued their current anti Parkinson's disease (anti-PD) medication regimen for the duration of the study. All anti-PD medications and medications to treat dyskinesia must have remained stable for the duration of the study unless adjustments were medically indicated. The Investigator provided the prescription for continued OMT.	Levodopa-Carbidopa Intestinal Gel (LCIG) n=25 Participants The total daily dose of infusion LCIG was composed of three components: (i) the morning dose, (ii) continuous maintenance infusion dose and (iii) extra doses. A temporary nasojejunal (NJ) tube may have been used initially with the infusion pump to determine a participant's response to this method of treatment and to optimize the dose of LCIG before treatment with a permanent percutaneous endoscopic gastrostomy - with jejunal extension (PEG-J) tube was started. Following optional NJ and/or PEG-J placement and, at the investigator's discretion, the participant may have begun initiation and titration of LCIG infusion on Day 1 once tube placement was confirmed. The dose of LCIG was adjusted to obtain the optimal clinical response. The rate of LCIG infusion is typically within the range of 1 to 10 mL/hour (20 to 200 mg of levodopa/hour) in most instances and runs over a period of 16 consecutive hours each day.
Mean Change From Baseline to Week 12 in ON Time Without Troublesome Dyskinesia	-0.12 hours Standard Error 0.63	3.15 hours Standard Error 0.69

SECONDARY outcome

Timeframe: Baseline, Week 12

The Parkinson's Disease Questionnaire-8 (PDQ-8) is a disease-specific instrument designed to measure aspects of health that are relevant to participants with PD, and which may not be included in general health status questionnaires. The PDQ-8 is a self-administered questionnaire. Each item is scored on the following 5-point scale: 0 = Never, 1 = Occasionally, 2 = Sometimes, 3 = Often, 4 = Always (or cannot do at all, if applicable). Higher scores are consistently associated with the more severe symptoms of the disease such as tremors and stiffness. The results are presented as a summary index. The PDQ-8 summary index ranges from 0 to 100, where lower scores indicate a better perceived health status. Negative changes from baseline indicate improvement.

Outcome measures

Outcome measures
Measure	Optimized Medical Treatment (OMT) n=29 Participants Participants randomized to OMT continued their current anti Parkinson's disease (anti-PD) medication regimen for the duration of the study. All anti-PD medications and medications to treat dyskinesia must have remained stable for the duration of the study unless adjustments were medically indicated. The Investigator provided the prescription for continued OMT.	Levodopa-Carbidopa Intestinal Gel (LCIG) n=25 Participants The total daily dose of infusion LCIG was composed of three components: (i) the morning dose, (ii) continuous maintenance infusion dose and (iii) extra doses. A temporary nasojejunal (NJ) tube may have been used initially with the infusion pump to determine a participant's response to this method of treatment and to optimize the dose of LCIG before treatment with a permanent percutaneous endoscopic gastrostomy - with jejunal extension (PEG-J) tube was started. Following optional NJ and/or PEG-J placement and, at the investigator's discretion, the participant may have begun initiation and titration of LCIG infusion on Day 1 once tube placement was confirmed. The dose of LCIG was adjusted to obtain the optimal clinical response. The rate of LCIG infusion is typically within the range of 1 to 10 mL/hour (20 to 200 mg of levodopa/hour) in most instances and runs over a period of 16 consecutive hours each day.
Mean Change From Baseline to Week 12 in Parkinson's Disease Questionnaire-8 (PDQ-8) Summary Index	-4.95 units on a scale Standard Error 3.11	-21.62 units on a scale Standard Error 3.47

SECONDARY outcome

Timeframe: Baseline, Week 12

The Clinical Global Impression of Change (CGI-C) score is a clinician's rating scale for assessing Global Improvement of Change. The CGI-C rates improvement by 7 categories: very much improved (1), much improved (2), minimally improved (3), no change (4), minimally worse (5), much worse (6), very much worse (7). The CGI-C score ranges from 1 to 7, with lower scores indicating improvement.

Outcome measures

Outcome measures
Measure	Optimized Medical Treatment (OMT) n=32 Participants Participants randomized to OMT continued their current anti Parkinson's disease (anti-PD) medication regimen for the duration of the study. All anti-PD medications and medications to treat dyskinesia must have remained stable for the duration of the study unless adjustments were medically indicated. The Investigator provided the prescription for continued OMT.	Levodopa-Carbidopa Intestinal Gel (LCIG) n=27 Participants The total daily dose of infusion LCIG was composed of three components: (i) the morning dose, (ii) continuous maintenance infusion dose and (iii) extra doses. A temporary nasojejunal (NJ) tube may have been used initially with the infusion pump to determine a participant's response to this method of treatment and to optimize the dose of LCIG before treatment with a permanent percutaneous endoscopic gastrostomy - with jejunal extension (PEG-J) tube was started. Following optional NJ and/or PEG-J placement and, at the investigator's discretion, the participant may have begun initiation and titration of LCIG infusion on Day 1 once tube placement was confirmed. The dose of LCIG was adjusted to obtain the optimal clinical response. The rate of LCIG infusion is typically within the range of 1 to 10 mL/hour (20 to 200 mg of levodopa/hour) in most instances and runs over a period of 16 consecutive hours each day.
Mean Clinical Global Impression of Change (CGI-C) Score at Week 12	4.58 units on a scale Standard Error 0.25	2.48 units on a scale Standard Error 0.28

SECONDARY outcome

Timeframe: Baseline, Week 12

The Unified Parkinson's Disease Rating Scale (UPDRS) is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The Part II score is the sum of the answers to the 13 questions related to Activities of Daily Living, and ranges from 0-52. Higher scores are associated with more disability. Negative values indicate improvement from baseline.

Outcome measures

Outcome measures
Measure	Optimized Medical Treatment (OMT) n=29 Participants Participants randomized to OMT continued their current anti Parkinson's disease (anti-PD) medication regimen for the duration of the study. All anti-PD medications and medications to treat dyskinesia must have remained stable for the duration of the study unless adjustments were medically indicated. The Investigator provided the prescription for continued OMT.	Levodopa-Carbidopa Intestinal Gel (LCIG) n=24 Participants The total daily dose of infusion LCIG was composed of three components: (i) the morning dose, (ii) continuous maintenance infusion dose and (iii) extra doses. A temporary nasojejunal (NJ) tube may have been used initially with the infusion pump to determine a participant's response to this method of treatment and to optimize the dose of LCIG before treatment with a permanent percutaneous endoscopic gastrostomy - with jejunal extension (PEG-J) tube was started. Following optional NJ and/or PEG-J placement and, at the investigator's discretion, the participant may have begun initiation and titration of LCIG infusion on Day 1 once tube placement was confirmed. The dose of LCIG was adjusted to obtain the optimal clinical response. The rate of LCIG infusion is typically within the range of 1 to 10 mL/hour (20 to 200 mg of levodopa/hour) in most instances and runs over a period of 16 consecutive hours each day.
Mean Change From Baseline to Week 12 in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Score (Activities of Daily Living)	0.21 units on a scale Standard Error 1.16	-5.33 units on a scale Standard Error 1.28

SECONDARY outcome

Timeframe: Baseline, Week 12

The Parkinson's Disease (PD) Symptom Diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected study visits. It reflects both time awake and time asleep. Daily totals are normalized to a 16-hour scale (i.e., 16 hours of awake time). The normalized totals for the 3 days prior to the visit are averaged for the analysis. ON time is when PD symptoms are well controlled by the drug, and OFF time is when PD symptoms are not adequately controlled by the drug. Negative change from baseline for OFF time indicates improvement.

Outcome measures

Outcome measures
Measure	Optimized Medical Treatment (OMT) n=28 Participants Participants randomized to OMT continued their current anti Parkinson's disease (anti-PD) medication regimen for the duration of the study. All anti-PD medications and medications to treat dyskinesia must have remained stable for the duration of the study unless adjustments were medically indicated. The Investigator provided the prescription for continued OMT.	Levodopa-Carbidopa Intestinal Gel (LCIG) n=25 Participants The total daily dose of infusion LCIG was composed of three components: (i) the morning dose, (ii) continuous maintenance infusion dose and (iii) extra doses. A temporary nasojejunal (NJ) tube may have been used initially with the infusion pump to determine a participant's response to this method of treatment and to optimize the dose of LCIG before treatment with a permanent percutaneous endoscopic gastrostomy - with jejunal extension (PEG-J) tube was started. Following optional NJ and/or PEG-J placement and, at the investigator's discretion, the participant may have begun initiation and titration of LCIG infusion on Day 1 once tube placement was confirmed. The dose of LCIG was adjusted to obtain the optimal clinical response. The rate of LCIG infusion is typically within the range of 1 to 10 mL/hour (20 to 200 mg of levodopa/hour) in most instances and runs over a period of 16 consecutive hours each day.
Mean Change From Baseline to Week 12 in OFF Time	0.18 hours Standard Error 0.49	-2.17 hours Standard Error 0.53

SECONDARY outcome

Timeframe: Baseline, Week 12

The Unified Parkinson's Disease Rating Scale (UPDRS) is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The Part III score is the sum of the 27 answers related to Motor Examination, and ranges from 0-108. Higher scores are associated with more disability. Negative values indicate improvement from baseline.

Outcome measures

Outcome measures
Measure	Optimized Medical Treatment (OMT) n=29 Participants Participants randomized to OMT continued their current anti Parkinson's disease (anti-PD) medication regimen for the duration of the study. All anti-PD medications and medications to treat dyskinesia must have remained stable for the duration of the study unless adjustments were medically indicated. The Investigator provided the prescription for continued OMT.	Levodopa-Carbidopa Intestinal Gel (LCIG) n=25 Participants The total daily dose of infusion LCIG was composed of three components: (i) the morning dose, (ii) continuous maintenance infusion dose and (iii) extra doses. A temporary nasojejunal (NJ) tube may have been used initially with the infusion pump to determine a participant's response to this method of treatment and to optimize the dose of LCIG before treatment with a permanent percutaneous endoscopic gastrostomy - with jejunal extension (PEG-J) tube was started. Following optional NJ and/or PEG-J placement and, at the investigator's discretion, the participant may have begun initiation and titration of LCIG infusion on Day 1 once tube placement was confirmed. The dose of LCIG was adjusted to obtain the optimal clinical response. The rate of LCIG infusion is typically within the range of 1 to 10 mL/hour (20 to 200 mg of levodopa/hour) in most instances and runs over a period of 16 consecutive hours each day.
Mean Change From Baseline to Week 12 in Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score (Motor Examination)	-0.87 units on a scale Standard Error 1.89	-4.93 units on a scale Standard Error 2.08

Adverse Events

Levodopa-Carbidopa Intestinal Gel (LCIG)

Serious events: 2 serious events

Other events: 15 other events

Deaths: 0 deaths

Optimized Medical Treatment (OMT)

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Levodopa-Carbidopa Intestinal Gel (LCIG) n=28 participants at risk The total daily dose of infusion LCIG was composed of three components: (i) the morning dose, (ii) continuous maintenance infusion dose and (iii) extra doses. A temporary nasojejunal (NJ) tube may have been used initially with the infusion pump to determine a participant's response to this method of treatment and to optimize the dose of LCIG before treatment with a permanent percutaneous endoscopic gastrostomy - with jejunal extension (PEG-J) tube was started. Following optional NJ and/or PEG-J placement and, at the investigator's discretion, the participant may have begun initiation and titration of LCIG infusion on Day 1 once tube placement was confirmed. The dose of LCIG was adjusted to obtain the optimal clinical response. The rate of LCIG infusion is typically within the range of 1 to 10 mL/hour (20 to 200 mg of levodopa/hour) in most instances and runs over a period of 16 consecutive hours each day.	Optimized Medical Treatment (OMT) n=33 participants at risk Participants randomized to OMT continued their current anti Parkinson's disease (anti-PD) medication regimen for the duration of the study. All anti-PD medications and medications to treat dyskinesia must have remained stable for the duration of the study unless adjustments were medically indicated. The Investigator provided the prescription for continued OMT.
Gastrointestinal disorders PNEUMOPERITONEUM	3.6% 1/28 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) collection: OMT (starting after the day of randomization until 30 days after the last visit, up to 18 weeks); LCIG group with study tube removal after the last study drug infusion (from the time of tube placement up to 30 days following tube removal, up to 16 weeks); other LCIG participants (starting with tube placement and up to 30 days following the last study visit, up to 16 weeks) TEAEs and SAEs are defined as any adverse event (AE) with an onset date starting after the day of randomization (OMT group) or from the time of tube placement (LCIG group) until 30 days after the last visit (OMT group), or up to 30 days following tube removal (LCIG group) or the last study visit (LCIG group) and were collected whether elicited or spontaneously reported by the participant.	0.00% 0/33 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) collection: OMT (starting after the day of randomization until 30 days after the last visit, up to 18 weeks); LCIG group with study tube removal after the last study drug infusion (from the time of tube placement up to 30 days following tube removal, up to 16 weeks); other LCIG participants (starting with tube placement and up to 30 days following the last study visit, up to 16 weeks) TEAEs and SAEs are defined as any adverse event (AE) with an onset date starting after the day of randomization (OMT group) or from the time of tube placement (LCIG group) until 30 days after the last visit (OMT group), or up to 30 days following tube removal (LCIG group) or the last study visit (LCIG group) and were collected whether elicited or spontaneously reported by the participant.
Infections and infestations CYSTITIS	3.6% 1/28 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) collection: OMT (starting after the day of randomization until 30 days after the last visit, up to 18 weeks); LCIG group with study tube removal after the last study drug infusion (from the time of tube placement up to 30 days following tube removal, up to 16 weeks); other LCIG participants (starting with tube placement and up to 30 days following the last study visit, up to 16 weeks) TEAEs and SAEs are defined as any adverse event (AE) with an onset date starting after the day of randomization (OMT group) or from the time of tube placement (LCIG group) until 30 days after the last visit (OMT group), or up to 30 days following tube removal (LCIG group) or the last study visit (LCIG group) and were collected whether elicited or spontaneously reported by the participant.	0.00% 0/33 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) collection: OMT (starting after the day of randomization until 30 days after the last visit, up to 18 weeks); LCIG group with study tube removal after the last study drug infusion (from the time of tube placement up to 30 days following tube removal, up to 16 weeks); other LCIG participants (starting with tube placement and up to 30 days following the last study visit, up to 16 weeks) TEAEs and SAEs are defined as any adverse event (AE) with an onset date starting after the day of randomization (OMT group) or from the time of tube placement (LCIG group) until 30 days after the last visit (OMT group), or up to 30 days following tube removal (LCIG group) or the last study visit (LCIG group) and were collected whether elicited or spontaneously reported by the participant.
Nervous system disorders SYNCOPE	3.6% 1/28 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) collection: OMT (starting after the day of randomization until 30 days after the last visit, up to 18 weeks); LCIG group with study tube removal after the last study drug infusion (from the time of tube placement up to 30 days following tube removal, up to 16 weeks); other LCIG participants (starting with tube placement and up to 30 days following the last study visit, up to 16 weeks) TEAEs and SAEs are defined as any adverse event (AE) with an onset date starting after the day of randomization (OMT group) or from the time of tube placement (LCIG group) until 30 days after the last visit (OMT group), or up to 30 days following tube removal (LCIG group) or the last study visit (LCIG group) and were collected whether elicited or spontaneously reported by the participant.	0.00% 0/33 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) collection: OMT (starting after the day of randomization until 30 days after the last visit, up to 18 weeks); LCIG group with study tube removal after the last study drug infusion (from the time of tube placement up to 30 days following tube removal, up to 16 weeks); other LCIG participants (starting with tube placement and up to 30 days following the last study visit, up to 16 weeks) TEAEs and SAEs are defined as any adverse event (AE) with an onset date starting after the day of randomization (OMT group) or from the time of tube placement (LCIG group) until 30 days after the last visit (OMT group), or up to 30 days following tube removal (LCIG group) or the last study visit (LCIG group) and were collected whether elicited or spontaneously reported by the participant.
Vascular disorders HYPERTENSION	3.6% 1/28 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) collection: OMT (starting after the day of randomization until 30 days after the last visit, up to 18 weeks); LCIG group with study tube removal after the last study drug infusion (from the time of tube placement up to 30 days following tube removal, up to 16 weeks); other LCIG participants (starting with tube placement and up to 30 days following the last study visit, up to 16 weeks) TEAEs and SAEs are defined as any adverse event (AE) with an onset date starting after the day of randomization (OMT group) or from the time of tube placement (LCIG group) until 30 days after the last visit (OMT group), or up to 30 days following tube removal (LCIG group) or the last study visit (LCIG group) and were collected whether elicited or spontaneously reported by the participant.	0.00% 0/33 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) collection: OMT (starting after the day of randomization until 30 days after the last visit, up to 18 weeks); LCIG group with study tube removal after the last study drug infusion (from the time of tube placement up to 30 days following tube removal, up to 16 weeks); other LCIG participants (starting with tube placement and up to 30 days following the last study visit, up to 16 weeks) TEAEs and SAEs are defined as any adverse event (AE) with an onset date starting after the day of randomization (OMT group) or from the time of tube placement (LCIG group) until 30 days after the last visit (OMT group), or up to 30 days following tube removal (LCIG group) or the last study visit (LCIG group) and were collected whether elicited or spontaneously reported by the participant.

Other adverse events

Other adverse events
Measure	Levodopa-Carbidopa Intestinal Gel (LCIG) n=28 participants at risk The total daily dose of infusion LCIG was composed of three components: (i) the morning dose, (ii) continuous maintenance infusion dose and (iii) extra doses. A temporary nasojejunal (NJ) tube may have been used initially with the infusion pump to determine a participant's response to this method of treatment and to optimize the dose of LCIG before treatment with a permanent percutaneous endoscopic gastrostomy - with jejunal extension (PEG-J) tube was started. Following optional NJ and/or PEG-J placement and, at the investigator's discretion, the participant may have begun initiation and titration of LCIG infusion on Day 1 once tube placement was confirmed. The dose of LCIG was adjusted to obtain the optimal clinical response. The rate of LCIG infusion is typically within the range of 1 to 10 mL/hour (20 to 200 mg of levodopa/hour) in most instances and runs over a period of 16 consecutive hours each day.	Optimized Medical Treatment (OMT) n=33 participants at risk Participants randomized to OMT continued their current anti Parkinson's disease (anti-PD) medication regimen for the duration of the study. All anti-PD medications and medications to treat dyskinesia must have remained stable for the duration of the study unless adjustments were medically indicated. The Investigator provided the prescription for continued OMT.
Gastrointestinal disorders ABDOMINAL PAIN	7.1% 2/28 • Number of events 2 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) collection: OMT (starting after the day of randomization until 30 days after the last visit, up to 18 weeks); LCIG group with study tube removal after the last study drug infusion (from the time of tube placement up to 30 days following tube removal, up to 16 weeks); other LCIG participants (starting with tube placement and up to 30 days following the last study visit, up to 16 weeks) TEAEs and SAEs are defined as any adverse event (AE) with an onset date starting after the day of randomization (OMT group) or from the time of tube placement (LCIG group) until 30 days after the last visit (OMT group), or up to 30 days following tube removal (LCIG group) or the last study visit (LCIG group) and were collected whether elicited or spontaneously reported by the participant.	0.00% 0/33 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) collection: OMT (starting after the day of randomization until 30 days after the last visit, up to 18 weeks); LCIG group with study tube removal after the last study drug infusion (from the time of tube placement up to 30 days following tube removal, up to 16 weeks); other LCIG participants (starting with tube placement and up to 30 days following the last study visit, up to 16 weeks) TEAEs and SAEs are defined as any adverse event (AE) with an onset date starting after the day of randomization (OMT group) or from the time of tube placement (LCIG group) until 30 days after the last visit (OMT group), or up to 30 days following tube removal (LCIG group) or the last study visit (LCIG group) and were collected whether elicited or spontaneously reported by the participant.
Gastrointestinal disorders DIARRHOEA	7.1% 2/28 • Number of events 2 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) collection: OMT (starting after the day of randomization until 30 days after the last visit, up to 18 weeks); LCIG group with study tube removal after the last study drug infusion (from the time of tube placement up to 30 days following tube removal, up to 16 weeks); other LCIG participants (starting with tube placement and up to 30 days following the last study visit, up to 16 weeks) TEAEs and SAEs are defined as any adverse event (AE) with an onset date starting after the day of randomization (OMT group) or from the time of tube placement (LCIG group) until 30 days after the last visit (OMT group), or up to 30 days following tube removal (LCIG group) or the last study visit (LCIG group) and were collected whether elicited or spontaneously reported by the participant.	0.00% 0/33 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) collection: OMT (starting after the day of randomization until 30 days after the last visit, up to 18 weeks); LCIG group with study tube removal after the last study drug infusion (from the time of tube placement up to 30 days following tube removal, up to 16 weeks); other LCIG participants (starting with tube placement and up to 30 days following the last study visit, up to 16 weeks) TEAEs and SAEs are defined as any adverse event (AE) with an onset date starting after the day of randomization (OMT group) or from the time of tube placement (LCIG group) until 30 days after the last visit (OMT group), or up to 30 days following tube removal (LCIG group) or the last study visit (LCIG group) and were collected whether elicited or spontaneously reported by the participant.
General disorders DRUG WITHDRAWAL SYNDROME	7.1% 2/28 • Number of events 2 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) collection: OMT (starting after the day of randomization until 30 days after the last visit, up to 18 weeks); LCIG group with study tube removal after the last study drug infusion (from the time of tube placement up to 30 days following tube removal, up to 16 weeks); other LCIG participants (starting with tube placement and up to 30 days following the last study visit, up to 16 weeks) TEAEs and SAEs are defined as any adverse event (AE) with an onset date starting after the day of randomization (OMT group) or from the time of tube placement (LCIG group) until 30 days after the last visit (OMT group), or up to 30 days following tube removal (LCIG group) or the last study visit (LCIG group) and were collected whether elicited or spontaneously reported by the participant.	0.00% 0/33 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) collection: OMT (starting after the day of randomization until 30 days after the last visit, up to 18 weeks); LCIG group with study tube removal after the last study drug infusion (from the time of tube placement up to 30 days following tube removal, up to 16 weeks); other LCIG participants (starting with tube placement and up to 30 days following the last study visit, up to 16 weeks) TEAEs and SAEs are defined as any adverse event (AE) with an onset date starting after the day of randomization (OMT group) or from the time of tube placement (LCIG group) until 30 days after the last visit (OMT group), or up to 30 days following tube removal (LCIG group) or the last study visit (LCIG group) and were collected whether elicited or spontaneously reported by the participant.
Infections and infestations URINARY TRACT INFECTION	7.1% 2/28 • Number of events 2 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) collection: OMT (starting after the day of randomization until 30 days after the last visit, up to 18 weeks); LCIG group with study tube removal after the last study drug infusion (from the time of tube placement up to 30 days following tube removal, up to 16 weeks); other LCIG participants (starting with tube placement and up to 30 days following the last study visit, up to 16 weeks) TEAEs and SAEs are defined as any adverse event (AE) with an onset date starting after the day of randomization (OMT group) or from the time of tube placement (LCIG group) until 30 days after the last visit (OMT group), or up to 30 days following tube removal (LCIG group) or the last study visit (LCIG group) and were collected whether elicited or spontaneously reported by the participant.	0.00% 0/33 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) collection: OMT (starting after the day of randomization until 30 days after the last visit, up to 18 weeks); LCIG group with study tube removal after the last study drug infusion (from the time of tube placement up to 30 days following tube removal, up to 16 weeks); other LCIG participants (starting with tube placement and up to 30 days following the last study visit, up to 16 weeks) TEAEs and SAEs are defined as any adverse event (AE) with an onset date starting after the day of randomization (OMT group) or from the time of tube placement (LCIG group) until 30 days after the last visit (OMT group), or up to 30 days following tube removal (LCIG group) or the last study visit (LCIG group) and were collected whether elicited or spontaneously reported by the participant.
Injury, poisoning and procedural complications FALL	21.4% 6/28 • Number of events 6 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) collection: OMT (starting after the day of randomization until 30 days after the last visit, up to 18 weeks); LCIG group with study tube removal after the last study drug infusion (from the time of tube placement up to 30 days following tube removal, up to 16 weeks); other LCIG participants (starting with tube placement and up to 30 days following the last study visit, up to 16 weeks) TEAEs and SAEs are defined as any adverse event (AE) with an onset date starting after the day of randomization (OMT group) or from the time of tube placement (LCIG group) until 30 days after the last visit (OMT group), or up to 30 days following tube removal (LCIG group) or the last study visit (LCIG group) and were collected whether elicited or spontaneously reported by the participant.	6.1% 2/33 • Number of events 3 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) collection: OMT (starting after the day of randomization until 30 days after the last visit, up to 18 weeks); LCIG group with study tube removal after the last study drug infusion (from the time of tube placement up to 30 days following tube removal, up to 16 weeks); other LCIG participants (starting with tube placement and up to 30 days following the last study visit, up to 16 weeks) TEAEs and SAEs are defined as any adverse event (AE) with an onset date starting after the day of randomization (OMT group) or from the time of tube placement (LCIG group) until 30 days after the last visit (OMT group), or up to 30 days following tube removal (LCIG group) or the last study visit (LCIG group) and were collected whether elicited or spontaneously reported by the participant.
Injury, poisoning and procedural complications PROCEDURAL PAIN	10.7% 3/28 • Number of events 3 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) collection: OMT (starting after the day of randomization until 30 days after the last visit, up to 18 weeks); LCIG group with study tube removal after the last study drug infusion (from the time of tube placement up to 30 days following tube removal, up to 16 weeks); other LCIG participants (starting with tube placement and up to 30 days following the last study visit, up to 16 weeks) TEAEs and SAEs are defined as any adverse event (AE) with an onset date starting after the day of randomization (OMT group) or from the time of tube placement (LCIG group) until 30 days after the last visit (OMT group), or up to 30 days following tube removal (LCIG group) or the last study visit (LCIG group) and were collected whether elicited or spontaneously reported by the participant.	0.00% 0/33 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) collection: OMT (starting after the day of randomization until 30 days after the last visit, up to 18 weeks); LCIG group with study tube removal after the last study drug infusion (from the time of tube placement up to 30 days following tube removal, up to 16 weeks); other LCIG participants (starting with tube placement and up to 30 days following the last study visit, up to 16 weeks) TEAEs and SAEs are defined as any adverse event (AE) with an onset date starting after the day of randomization (OMT group) or from the time of tube placement (LCIG group) until 30 days after the last visit (OMT group), or up to 30 days following tube removal (LCIG group) or the last study visit (LCIG group) and were collected whether elicited or spontaneously reported by the participant.
Musculoskeletal and connective tissue disorders MUSCLE SPASMS	7.1% 2/28 • Number of events 2 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) collection: OMT (starting after the day of randomization until 30 days after the last visit, up to 18 weeks); LCIG group with study tube removal after the last study drug infusion (from the time of tube placement up to 30 days following tube removal, up to 16 weeks); other LCIG participants (starting with tube placement and up to 30 days following the last study visit, up to 16 weeks) TEAEs and SAEs are defined as any adverse event (AE) with an onset date starting after the day of randomization (OMT group) or from the time of tube placement (LCIG group) until 30 days after the last visit (OMT group), or up to 30 days following tube removal (LCIG group) or the last study visit (LCIG group) and were collected whether elicited or spontaneously reported by the participant.	0.00% 0/33 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) collection: OMT (starting after the day of randomization until 30 days after the last visit, up to 18 weeks); LCIG group with study tube removal after the last study drug infusion (from the time of tube placement up to 30 days following tube removal, up to 16 weeks); other LCIG participants (starting with tube placement and up to 30 days following the last study visit, up to 16 weeks) TEAEs and SAEs are defined as any adverse event (AE) with an onset date starting after the day of randomization (OMT group) or from the time of tube placement (LCIG group) until 30 days after the last visit (OMT group), or up to 30 days following tube removal (LCIG group) or the last study visit (LCIG group) and were collected whether elicited or spontaneously reported by the participant.
Nervous system disorders PARKINSON'S DISEASE	3.6% 1/28 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) collection: OMT (starting after the day of randomization until 30 days after the last visit, up to 18 weeks); LCIG group with study tube removal after the last study drug infusion (from the time of tube placement up to 30 days following tube removal, up to 16 weeks); other LCIG participants (starting with tube placement and up to 30 days following the last study visit, up to 16 weeks) TEAEs and SAEs are defined as any adverse event (AE) with an onset date starting after the day of randomization (OMT group) or from the time of tube placement (LCIG group) until 30 days after the last visit (OMT group), or up to 30 days following tube removal (LCIG group) or the last study visit (LCIG group) and were collected whether elicited or spontaneously reported by the participant.	6.1% 2/33 • Number of events 2 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) collection: OMT (starting after the day of randomization until 30 days after the last visit, up to 18 weeks); LCIG group with study tube removal after the last study drug infusion (from the time of tube placement up to 30 days following tube removal, up to 16 weeks); other LCIG participants (starting with tube placement and up to 30 days following the last study visit, up to 16 weeks) TEAEs and SAEs are defined as any adverse event (AE) with an onset date starting after the day of randomization (OMT group) or from the time of tube placement (LCIG group) until 30 days after the last visit (OMT group), or up to 30 days following tube removal (LCIG group) or the last study visit (LCIG group) and were collected whether elicited or spontaneously reported by the participant.
Psychiatric disorders ANXIETY	7.1% 2/28 • Number of events 2 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) collection: OMT (starting after the day of randomization until 30 days after the last visit, up to 18 weeks); LCIG group with study tube removal after the last study drug infusion (from the time of tube placement up to 30 days following tube removal, up to 16 weeks); other LCIG participants (starting with tube placement and up to 30 days following the last study visit, up to 16 weeks) TEAEs and SAEs are defined as any adverse event (AE) with an onset date starting after the day of randomization (OMT group) or from the time of tube placement (LCIG group) until 30 days after the last visit (OMT group), or up to 30 days following tube removal (LCIG group) or the last study visit (LCIG group) and were collected whether elicited or spontaneously reported by the participant.	0.00% 0/33 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) collection: OMT (starting after the day of randomization until 30 days after the last visit, up to 18 weeks); LCIG group with study tube removal after the last study drug infusion (from the time of tube placement up to 30 days following tube removal, up to 16 weeks); other LCIG participants (starting with tube placement and up to 30 days following the last study visit, up to 16 weeks) TEAEs and SAEs are defined as any adverse event (AE) with an onset date starting after the day of randomization (OMT group) or from the time of tube placement (LCIG group) until 30 days after the last visit (OMT group), or up to 30 days following tube removal (LCIG group) or the last study visit (LCIG group) and were collected whether elicited or spontaneously reported by the participant.
Psychiatric disorders DEPRESSION	7.1% 2/28 • Number of events 2 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) collection: OMT (starting after the day of randomization until 30 days after the last visit, up to 18 weeks); LCIG group with study tube removal after the last study drug infusion (from the time of tube placement up to 30 days following tube removal, up to 16 weeks); other LCIG participants (starting with tube placement and up to 30 days following the last study visit, up to 16 weeks) TEAEs and SAEs are defined as any adverse event (AE) with an onset date starting after the day of randomization (OMT group) or from the time of tube placement (LCIG group) until 30 days after the last visit (OMT group), or up to 30 days following tube removal (LCIG group) or the last study visit (LCIG group) and were collected whether elicited or spontaneously reported by the participant.	3.0% 1/33 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) collection: OMT (starting after the day of randomization until 30 days after the last visit, up to 18 weeks); LCIG group with study tube removal after the last study drug infusion (from the time of tube placement up to 30 days following tube removal, up to 16 weeks); other LCIG participants (starting with tube placement and up to 30 days following the last study visit, up to 16 weeks) TEAEs and SAEs are defined as any adverse event (AE) with an onset date starting after the day of randomization (OMT group) or from the time of tube placement (LCIG group) until 30 days after the last visit (OMT group), or up to 30 days following tube removal (LCIG group) or the last study visit (LCIG group) and were collected whether elicited or spontaneously reported by the participant.

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