A Study to Assess the Efficacy, Safety and Tolerability of ABT-SLV187 Monotherapy in Subjects With Advanced Parkinson's Disease (PD) and Persistent Motor Complications, Despite Optimized Treatment With Available Anti-Parkinsonian Medications

• Sponsor: AbbVie (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01960842
• Collaborator: (none)
• Enrollment: 31
• Arm: 1
• Duration (Months): 17

Study Details

Study Description

Brief Summary

The primary objective of this study is to measure the efficacy of ABT-SLV187 in subjects with advanced Parkinson's disease.

Condition or Disease	Intervention/Treatment	Phase
Advanced Parkinson's Disease	Drug: Levodopa-carbidopa intestinal gel; Device: CADD-Legacy® 1400 ambulatory infusion pump; Device: PEG tube; Device: J-tube	Phase 3

Detailed Description

The study was composed of a screening period followed by 2 sequential on-treatment periods, as follows:

• Screening Period (up to 28 days): determination of eligibility and discontinuation of antiparkinsonian disease medications other than levodopa-carbidopa immediate release (LC-oral) prior to nasojejunal (N-J) tube placement.

• N-J Test Period (2 to 14 days): first hospitalization period, Baseline assessments, placement of N-J tube, and optimization of levodopa-carbidopa intestinal gel (LCIG) treatment via N-J tube and infusion pump (participant was hospitalized for N-J tube placement but hospitalization was not required for entire duration of LCIG treatment optimization).

• PEG-J Period (12 weeks): second hospitalization period; placement of PEG-J tube; further optimization of LCIG treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Single-Arm, Baseline-Controlled, Multicenter Study to Evaluate the Efficacy, Safety and Tolerability of ABT-SLV187 Monotherapy in Subjects With Advanced Parkinson's Disease and Persistent Motor-Complications Despite Optimized Treatment With Available Anti-Parkinsonian Medication
• Study Start Date: Oct 1, 2013
• Actual Primary Completion Date: Mar 1, 2015
• Actual Study Completion Date: Mar 1, 2015

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Levodopa-Carbidopa Intestinal Gel (LCIG) All participants received LCIG via the N-J tube during the nasojejunal (N-J) Test Period and delivered to the proximal small intestine via percutaneous endoscopic gastrostomy - with jejunal extension tube (PEG-J) during the Post-PEG-J Long-Term Treatment Period. The starting dose was individually determined based on the daily dose of oral levodopa prior to study enrollment. The infusion dose was individually optimized for each participant on the basis of response and potential adverse events. During the PEG-J Period, LCIG was expected to be infused continuously over approximately 16 hours daily with a rate of infusion ranging from 1 to 10 mL/hour (20 to 200 mg of levodopa/hour).

Drug: Levodopa-carbidopa intestinal gel; Dose levels will be individually optimized. Infusion should be kept within a range of 0.5-10 mL/hour (10-200 mg levodopa/hour) and is usually 2-6 mL/hour (40-120 mg levodopa/hour); Other Names: ABT-SLV187 LCIG ; Device: CADD-Legacy® 1400 ambulatory infusion pump; Device: PEG tube; percutaneous endoscopic gastrostomy tube; Device: J-tube; jejunal tube

Outcome Measures

Primary Outcome Measures

1. Average Daily Normalized "Off" Time: Change From Baseline To The Final PEG-J Visit [Baseline (end of screening period) and Final PEG-J Visit (up to week 12)]

   Based on the Parkinson's Disease Symptom Diary. "On" time is when PD symptoms are well controlled by the drug. "Off" time is when PD symptoms are not adequately controlled by the drug. The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic 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. Negative change from baseline for "off" time indicates improvement.

Secondary Outcome Measures

1. Average Daily Normalized "On" Time Without Troublesome Dyskinesia: Change From Baseline To The Final PEG-J Visit [Baseline (end of screening period) and Final PEG-J Visit (up to week 12)]

   Based on the Parkinson's Disease Symptom Diary. "On" time is when PD symptoms are well controlled by the drug. "Off" time is when PD symptoms are not adequately controlled by the drug. The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic 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. Positive change from baseline for "on" time indicates improvement.

2. Parkinson's Disease Questionnaire (PDQ-39) Summary Index: Change From Baseline To The Final PEG-J Visit [Baseline (end of screening period) and Final PEG-J Visit (up to week 12)]

   The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. These include: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort. The PDQ-39 Summary Index is the sum of all answers divided by the highest score possible (i.e. number of answers multiplied by 4) which is multiplied by 100 to put the score on a 0-100 scale. Higher scores are associated with more severe symptoms.

3. Clinical Global Impression - Change (CGI-I) Score at the Final PEG-J Visit [Final PEG-J Visit (up to week 12)]

   The CGI-I is a global assessment by the Investigator of the change in clinical status since the start of treatment. The CGI-I ratings are as follows: 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse.

4. Patient Global Impression of Change (PGI-C) Score at the Final PEG-J Visit [Final PEG-J Visit (up to week 12)]

   The PGI-C is a 7-point response scale. The subjects were to rate their change in status from Screening Visit 1 using the following 7-point scale: 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, 7 = Very much worse. The responses of "Minimally improved," "Much improved," and "Very much improved" on the PGI-C were used to define responders.

5. Unified Parkinson's Disease Rating Scale (UPDRS) Part II Score: Change From Baseline To The Final PEG-J Visit [Baseline (end of screening period) and Final PEG-J Visit (up to week 12)]

   The 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 that comprise Part II, each of which are measured on a 5-point scale (0-4). The Part II score ranges from 0-52 and higher scores are associated with more disability.

6. Unified Parkinson's Disease Rating Scale (UPDRS) Part IIl Score: Change From Baseline To The Final PEG-J Visit [Baseline (end of screening period) and Final PEG-J Visit (up to week 12)]

   The 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 provided to the 14 Part III questions, each of which are measured on a 5-point scale (0-4). The Part III score ranges from 0-108 and higher scores are associated with more disability.

7. Average Daily Normalized "On" Time With Troublesome Dyskinesia: Change From Baseline To The Final PEG-J Visit [Baseline (end of screening period) and Final PEG-J Visit (up to week 12)]

   Based on the Parkinson's Disease Symptom Diary. "On" time is when PD symptoms are well controlled by the drug. "Off" time is when PD symptoms are not adequately controlled by the drug. The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic 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. Positive change from baseline for "on" time indicates improvement.

8. Parkinson's Disease Questionnaire (PDQ-39) Mobility, Emotional Well-Being, Stigma, Social Support, Cognition, Communication, and Bodily Discomfort Domain Scores: Change From Baseline To The Final PEG-J Visit [Baseline (end of screening period) and Final PEG-J Visit (up to week 12)]

   The PDQ-39 is a self-administered questionnaire which comprises 39 items (each question answered on a 5-point scale) addressing 8 domains of health in Parkinson's disease patients: Mobility (e.g., fear of falling when walking) includes 10 questions; Emotional Well-being (e.g., feelings of isolation) includes 6 questions; Stigma (e.g., social embarrassment) includes 4 questions; Social Support includes 3 questions; Cognition includes 4 questions; Communication includes 3 questions; and Bodily Discomfort includes 3 questions. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness.

9. Unified Parkinson's Disease Rating Scale (UPDRS) Total Score: Change From Baseline To The Final PEG-J Visit [Baseline and Final PEG-J Visit (up to Week 12)]

   The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The total score is the sum of the responses to the 31 questions (44 answers) that comprise Parts I-III of the scale. The total score will range from 0 to176, with 176 representing the worst (total) disability, and 0 representing no disability.

10. Unified Parkinson's Disease Rating Scale (UPDRS) Part I Score: Change From Baseline To The Final PEG-J Visit [Baseline (end of screening period) and Final PEG-J Visit (up to week 12)]

    The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The Part I Score is the sum of the answers to the 4 questions that comprise Part I, each of which are measured on a 5-point scale (0-4). The Part I score ranges from 0 to 16 and higher scores are associated with more disability.

11. Unified Parkinson's Disease Rating Scale (UPDRS) Part IV Score: Change From Baseline To The Final PEG-J Visit [Baseline (end of screening period) and Final PEG-J Visit (up to week 12)]

    The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The Part IV Score is the sum of the answers to the 11 questions that comprise Part IV, each of which are measured on a 5-point scale (0-4) or a 2-point scale (0 or 1). The Part IV score ranges from 0 to 23 and higher scores are associated with more disability.

12. Average Daily Normalized "Off" Time Excluding Subjects Who Did Not Receive LCIG During the Entire PEG-J Period: Change From Baseline To The Final PEG-J Visit [Baseline (end of screening period) and Final PEG-J Visit (up to week 12)]

    Based on the Parkinson's Disease Symptom Diary. "On" time is when PD symptoms are well controlled by the drug. "Off" time is when PD symptoms are not adequately controlled by the drug. The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic 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. Negative change from baseline for "off" time indicates improvement.

13. Average Daily Normalized "Off" Time Including All PD Diaries Regardless if They Were Completed After the Subject Had Used a Concomitant Anti-Parkinsonian Medication: Change From Baseline To The Final PEG-J Visit [Baseline (end of screening period) and Final PEG-J Visit (up to week 12)]

    Based on the Parkinson's Disease Symptom Diary. "On" time is when PD symptoms are well controlled by the drug. "Off" time is when PD symptoms are not adequately controlled by the drug. The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic 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. Negative change from baseline for "off" time indicates improvement.

14. Average Daily Normalized "Off" Time at Baseline and Each Visit: Change From Baseline To The Final PEG-J Visit [Baseline (end of screening period) and Weeks 2, 4, 6, 8, 10, and 12]

    Based on the Parkinson's Disease Symptom Diary. "On" time is when PD symptoms are well controlled by the drug. "Off" time is when PD symptoms are not adequately controlled by the drug. The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic 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. n= the number of participants with available data at each time point.

15. Number of Participants With Treatment-emergent Adverse Events (TEAEs) [From N-J placement to the end of study or early termination of treatment, including the removal of PEG-J (up to 17 weeks), plus 30 days.]

    An adverse event (AE) is any untoward medical occurrence in a participant which does not necessarily have a causal relationship with this treatment. A serious AE (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent AEs (TEAEs) are defined as any event that began or worsened in severity after N-J placement. The investigator assessed the relationship of each event to the use of study drug as Reasonable Possibility or No Reasonable Possibility. For more details on adverse events please see the AE section below.

16. Number of Participants With Potentially Clinically Significant Vital Sign Parameters [From Baseline (end of screening period) to Final PEG-J Visit (up to week 12)]

    Terms abbreviated in the table include supine systolic blood pressure (SuSBP), standing systolic blood pressure (StSBP), orthostatic systolic blood pressure (OSBP), supine diastolic blood pressure (SuDBP), standing diastolic blood pressure (StDBP), orthostatic diastolic blood pressure (ODBP), supine pulse (SuP) in beats per minute (bpm), standing pulse (StP), body temperature (Temp), and baseline (BL). Increase and decrease are signified by ↑ and ↓, respectively.

17. Number of Participants With Potentially Clinically Significant Values for Hematology Parameters [From Baseline (end of screening period) to Final PEG-J Visit (up to week 12)]

    Terms abbreviated in the table include females (f), males (m), and femtoliters (fL).

18. Number of Participants With Potentially Clinically Significant Values for Clinical Chemistry Parameters [From Baseline (end of screening period) to Final PEG-J Visit (up to week 12)]

    Terms abbreviated in the table include upper limit of normal (ULN), male (m), and female (f).

19. Number of Participants With Potentially Clinically Significant Values for 12-lead Electrocardiogram (ECG) [From Baseline (end of screening period) to Final PEG-J Visit (up to week 12)]

    Terms abbreviated in the table include heart rate (HR) in beats per minute (bpm), PR interval (PRI), QT interval corrected for heart rate using Bazett's formula (QTcB), QT interval corrected for heart rate using Fridericia's formula (QTcF), and baseline (BL). Increase and decrease are signified by ↑ and ↓, respectively. n = the number of participants with available data at each time point.

Other Outcome Measures

1. Neurological Examination [From Baseline (end of screening period) to Final PEG-J Visit (up to week 12)]

   Any abnormal findings are recorded as an adverse event after the first study drug administration; please see the AE section below. Further analysis for neurological examination findings was not performed per protocol.

2. Physical Examination [From Baseline (end of screening period) to Final PEG-J Visit (up to week 12)]

   Any abnormal findings are recorded as an adverse event after the first study drug administration; please see the AE section below. Further analysis for physical examination findings was not performed per protocol.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Diagnosis of idiopathic Parkinson's disease according to the United Kingdom Parkinson's Disease Society (UKPDS) Brain Bank Criteria.

2. Subjects have 4 or 5 in modified Hohn and Yahr (H & Y) classification of disease severity at "Off" state determined by the UPDRS Part V at Screening Visit 1.

3. The subject's advanced Parkinson's disease must be levodopa-responsive as judged by the Investigator.

4. Subjects have had optimal treatment with available Parkinson's disease medication as defined by local standards of care and, based upon the judgment of the Investigator, and their symptoms are judged inadequately controlled on this optimized treatment. Optimized treatment is defined as the maximum therapeutic effect obtained with available anti-parkinsonian pharmacological therapy when no further improvement is expected regardless of any additional manipulations of levodopa and/or other anti parkinsonian medication; this will be based on the Investigator's best clinical judgment.

5. Presence of a recognizable "Off" and "On" state (motor fluctuations) as confirmed by UPDRS Part III (in both "On" and "Off" states), and by the Parkinson's Disease Diary© which must be observed and confirmed at Screening Visit 1.

6. Subjects must be experiencing a minimum of 3 hours per day of "Off" time, as estimated by the Investigator and supported by the UPDRS at Screening Visit 1 and the Parkinson's Disease Diaries at baseline. The "Off" time must occur during a continuous 16-hour interval, including the portion of the day during which the subject is awake the majority of the time (e.g., 5 AM to 9 PM, 7 AM to 11 PM).

Exclusion Criteria:

1. Parkinson's disease diagnosis is unclear or a suspicion of other parkinsonian syndromes exists, such as secondary Parkinsonism (caused by drugs, toxins, infectious agents, vascular disease, trauma, brain neoplasm), Parkinson's-plus syndromes (e.g., multiple system atrophy, progressive supranuclear palsy) or the other neurodegenerative diseases that might mimic the symptoms of Parkinson's disease .

2. Subjects who have undergone neurosurgery for the treatment of Parkinson's disease .

3. Current primary psychiatric diagnosis of acute psychotic disorder or other uncontrolled primary psychiatric diagnoses, (e.g., bipolar disorder or major depressive disorder per Diagnostic and Statistical Manual of Mental Disorders 4th edition, Text Revision (DSM-IV-TR) criteria.

4. Alzheimer's disease; or other significant cognitive impairment or dementia (defined as Mini-Mental State Examination (MMSE) total score < 24).

5. Subject has significant current suicidal ideation within the previous year as evidenced by answering "yes" to questions 4 or 5 on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale (C-SSRS) completed at Screening or any history of suicide attempts.

6. A low B12 level or low-normal B12 level (less than 300 pg/mL) with elevated methylmalonic acid (MMA). Note: Abnormal Vitamin B12 of questionable clinical significance (i.e., indeterminate or low normal results) prior to or at Screening Visit 2 require appropriate interpretation in conjunction with MMA and homocysteine laboratory values prior to proceeding further into the study.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• AbbVie

Investigators

• Study Director: Masayoshi Yanagawa, PhD, AbbVie Japan

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT01960842
• Other Study ID Numbers: M12-921
• First Posted: Oct 11, 2013
• Last Update Posted: May 30, 2018
• Last Verified: Apr 1, 2016

• Keywords provided by AbbVie: levodopa; Advanced Parkinson's Disease; carbidopa; levodopa-carbidopa intestinal gel; Safety and Efficacy
• Additional relevant MeSH terms: Parkinson Disease; Levodopa; Carbidopa; Carbidopa, levodopa drug combination

Study Results

Participant Flow

Pre-assignment Detail	A total of 31 participants were enrolled and had undergone the N-J placement procedure and were included in the Safety Analysis Set; 1 participant did not have at least 1 post-PEG efficacy assessment and was excluded from the Full Analysis Set (FAS), which consisted of 30 participants.

Arm/Group Title	Levodopa-Carbidopa Intestinal Gel (LCIG)
Arm/Group Description	All participants received LCIG via the N-J tube during the nasojejunal (N-J) Test Period and delivered to the proximal small intestine via percutaneous endoscopic gastrostomy - with jejunal extension tube (PEG-J) during the Post-PEG-J Long-Term Treatment Period. The starting dose was individually determined based on the daily dose of oral levodopa prior to study enrollment. The infusion dose was individually optimized for each participant on the basis of response and potential adverse events. During the PEG-J Period, LCIG was expected to be infused continuously over approximately 16 hours daily with a rate of infusion ranging from 1 to 10 mL/hour (20 to 200 mg of levodopa/hour).
Period Title: Overall Study
STARTED	31
COMPLETED	28
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Levodopa-Carbidopa Intestinal Gel (LCIG)
Arm/Group Description	All participants received LCIG via the N-J tube during the nasojejunal (N-J) Test Period and delivered to the proximal small intestine via percutaneous endoscopic gastrostomy - with jejunal extension tube (PEG-J) during the Post-PEG-J Long-Term Treatment Period. The starting dose was individually determined based on the daily dose of oral levodopa prior to study enrollment. The infusion dose was individually optimized for each participant on the basis of response and potential adverse events. During the PEG-J Period, LCIG was expected to be infused continuously over approximately 16 hours daily with a rate of infusion ranging from 1 to 10 mL/hour (20 to 200 mg of levodopa/hour).
Overall Participants	31
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.6 (10.50)
Sex: Female, Male (Count of Participants)
Female	19 61.3%
Male	12 38.7%
Duration of Parkinson's Disease Since Initial Diagnosis (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	12.4 (5.08)

Outcome Measures

1. Primary Outcome

Title	Average Daily Normalized "Off" Time: Change From Baseline To The Final PEG-J Visit
Description	Based on the Parkinson's Disease Symptom Diary. "On" time is when PD symptoms are well controlled by the drug. "Off" time is when PD symptoms are not adequately controlled by the drug. The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic 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. Negative change from baseline for "off" time indicates improvement.
Time Frame	Baseline (end of screening period) and Final PEG-J Visit (up to week 12)

Outcome Measure Data

Analysis Population Description

All participants in the Full Analysis Set (FAS; all enrolled participants who received at least 1 dose of LCIG infusion during the PEG-J Period and had data for baseline and at least 1 post-PEG-J efficacy assessment) with available data.

Arm/Group Title	Levodopa-Carbidopa Intestinal Gel (LCIG)
Arm/Group Description	All participants received LCIG via the N-J tube during the nasojejunal (N-J) Test Period and delivered to the proximal small intestine via percutaneous endoscopic gastrostomy - with jejunal extension tube (PEG-J) during the Post-PEG-J Long-Term Treatment Period. The starting dose was individually determined based on the daily dose of oral levodopa prior to study enrollment. The infusion dose was individually optimized for each participant on the basis of response and potential adverse events. During the PEG-J Period, LCIG was expected to be infused continuously over approximately 16 hours daily with a rate of infusion ranging from 1 to 10 mL/hour (20 to 200 mg of levodopa/hour).
Measure Participants	29
Baseline	7.37 (2.263)
Last PEG-J visit	2.72 (2.320)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levodopa-Carbidopa Intestinal Gel (LCIG)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	One-sample t-test, 2-sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-4.64
	Confidence Interval	(2-Sided) 95%; -5.78 to -3.50
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Average Daily Normalized "On" Time Without Troublesome Dyskinesia: Change From Baseline To The Final PEG-J Visit
Description	Based on the Parkinson's Disease Symptom Diary. "On" time is when PD symptoms are well controlled by the drug. "Off" time is when PD symptoms are not adequately controlled by the drug. The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic 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. Positive change from baseline for "on" time indicates improvement.
Time Frame	Baseline (end of screening period) and Final PEG-J Visit (up to week 12)

Outcome Measure Data

Analysis Population Description

All participants in the FAS with available data.

Arm/Group Title	Levodopa-Carbidopa Intestinal Gel (LCIG)
Arm/Group Description	All participants received LCIG via the N-J tube during the nasojejunal (N-J) Test Period and delivered to the proximal small intestine via percutaneous endoscopic gastrostomy - with jejunal extension tube (PEG-J) during the Post-PEG-J Long-Term Treatment Period. The starting dose was individually determined based on the daily dose of oral levodopa prior to study enrollment. The infusion dose was individually optimized for each participant on the basis of response and potential adverse events. During the PEG-J Period, LCIG was expected to be infused continuously over approximately 16 hours daily with a rate of infusion ranging from 1 to 10 mL/hour (20 to 200 mg of levodopa/hour).
Measure Participants	29
Baseline	7.52 (2.505)
Last PEG-J visit	13.10 (2.453)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levodopa-Carbidopa Intestinal Gel (LCIG)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	One-sample t-test, 2-sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	5.58
	Confidence Interval	(2-Sided) 95%; 4.21 to 6.95
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Parkinson's Disease Questionnaire (PDQ-39) Summary Index: Change From Baseline To The Final PEG-J Visit
Description	The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. These include: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort. The PDQ-39 Summary Index is the sum of all answers divided by the highest score possible (i.e. number of answers multiplied by 4) which is multiplied by 100 to put the score on a 0-100 scale. Higher scores are associated with more severe symptoms.
Time Frame	Baseline (end of screening period) and Final PEG-J Visit (up to week 12)

Outcome Measure Data

Analysis Population Description

All participants in the FAS.

Arm/Group Title	Levodopa-Carbidopa Intestinal Gel (LCIG)
Arm/Group Description	All participants received LCIG via the N-J tube during the nasojejunal (N-J) Test Period and delivered to the proximal small intestine via percutaneous endoscopic gastrostomy - with jejunal extension tube (PEG-J) during the Post-PEG-J Long-Term Treatment Period. The starting dose was individually determined based on the daily dose of oral levodopa prior to study enrollment. The infusion dose was individually optimized for each participant on the basis of response and potential adverse events. During the PEG-J Period, LCIG was expected to be infused continuously over approximately 16 hours daily with a rate of infusion ranging from 1 to 10 mL/hour (20 to 200 mg of levodopa/hour).
Measure Participants	30
Baseline	35.5 (13.75)
Last PEG-J visit	23.5 (13.59)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levodopa-Carbidopa Intestinal Gel (LCIG)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	One-sample t-test, 2-sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-12.0
	Confidence Interval	(2-Sided) 95%; -16.3 to -7.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Clinical Global Impression - Change (CGI-I) Score at the Final PEG-J Visit
Description	The CGI-I is a global assessment by the Investigator of the change in clinical status since the start of treatment. The CGI-I ratings are as follows: 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse.
Time Frame	Final PEG-J Visit (up to week 12)

Outcome Measure Data

Analysis Population Description

All participants in the FAS with available data.

Arm/Group Title	Levodopa-Carbidopa Intestinal Gel (LCIG)
Arm/Group Description	All participants received LCIG via the N-J tube during the nasojejunal (N-J) Test Period and delivered to the proximal small intestine via percutaneous endoscopic gastrostomy - with jejunal extension tube (PEG-J) during the Post-PEG-J Long-Term Treatment Period. The starting dose was individually determined based on the daily dose of oral levodopa prior to study enrollment. The infusion dose was individually optimized for each participant on the basis of response and potential adverse events. During the PEG-J Period, LCIG was expected to be infused continuously over approximately 16 hours daily with a rate of infusion ranging from 1 to 10 mL/hour (20 to 200 mg of levodopa/hour).
Measure Participants	29
Mean (Standard Deviation) [units on a scale]	1.9 (0.77)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levodopa-Carbidopa Intestinal Gel (LCIG)
	Comments	The p-value is based on a one-sample Wilcoxon signed-rank test with the hypothesis of no change (score = 4).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon signed-rank test
	Comments
Method of Estimation	Estimation Parameter	Mean change from score = 4
	Estimated Value	-2.1
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 0.77
	Estimation Comments

5. Secondary Outcome

Title	Patient Global Impression of Change (PGI-C) Score at the Final PEG-J Visit
Description	The PGI-C is a 7-point response scale. The subjects were to rate their change in status from Screening Visit 1 using the following 7-point scale: 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, 7 = Very much worse. The responses of "Minimally improved," "Much improved," and "Very much improved" on the PGI-C were used to define responders.
Time Frame	Final PEG-J Visit (up to week 12)

Outcome Measure Data

Analysis Population Description

All participants in the FAS with available data.

Arm/Group Title	Levodopa-Carbidopa Intestinal Gel (LCIG)
Arm/Group Description	All participants received LCIG via the N-J tube during the nasojejunal (N-J) Test Period and delivered to the proximal small intestine via percutaneous endoscopic gastrostomy - with jejunal extension tube (PEG-J) during the Post-PEG-J Long-Term Treatment Period. The starting dose was individually determined based on the daily dose of oral levodopa prior to study enrollment. The infusion dose was individually optimized for each participant on the basis of response and potential adverse events. During the PEG-J Period, LCIG was expected to be infused continuously over approximately 16 hours daily with a rate of infusion ranging from 1 to 10 mL/hour (20 to 200 mg of levodopa/hour).
Measure Participants	29
Mean (Standard Deviation) [units on a scale]	2.0 (0.94)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levodopa-Carbidopa Intestinal Gel (LCIG)
	Comments	The p-value is based on a one-sample Wilcoxon signed-rank test with the hypothesis of no change (score = 4).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon signed-rank test
	Comments
Method of Estimation	Estimation Parameter	Mean change from score = 4
	Estimated Value	-2.0
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 0.94
	Estimation Comments

6. Secondary Outcome

Title	Unified Parkinson's Disease Rating Scale (UPDRS) Part II Score: Change From Baseline To The Final PEG-J Visit
Description	The 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 that comprise Part II, each of which are measured on a 5-point scale (0-4). The Part II score ranges from 0-52 and higher scores are associated with more disability.
Time Frame	Baseline (end of screening period) and Final PEG-J Visit (up to week 12)

Outcome Measure Data

Analysis Population Description

All participants in the FAS.

Arm/Group Title	Levodopa-Carbidopa Intestinal Gel (LCIG)
Arm/Group Description	All participants received LCIG via the N-J tube during the nasojejunal (N-J) Test Period and delivered to the proximal small intestine via percutaneous endoscopic gastrostomy - with jejunal extension tube (PEG-J) during the Post-PEG-J Long-Term Treatment Period. The starting dose was individually determined based on the daily dose of oral levodopa prior to study enrollment. The infusion dose was individually optimized for each participant on the basis of response and potential adverse events. During the PEG-J Period, LCIG was expected to be infused continuously over approximately 16 hours daily with a rate of infusion ranging from 1 to 10 mL/hour (20 to 200 mg of levodopa/hour).
Measure Participants	30
Baseline	9.4 (6.63)
Last PEG-J visit	7.6 (6.93)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levodopa-Carbidopa Intestinal Gel (LCIG)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.101
	Comments
	Method	One-sample t-test, 2-sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.8
	Confidence Interval	(2-Sided) 95%; -4.0 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Unified Parkinson's Disease Rating Scale (UPDRS) Part IIl Score: Change From Baseline To The Final PEG-J Visit
Description	The 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 provided to the 14 Part III questions, each of which are measured on a 5-point scale (0-4). The Part III score ranges from 0-108 and higher scores are associated with more disability.
Time Frame	Baseline (end of screening period) and Final PEG-J Visit (up to week 12)

Outcome Measure Data

Analysis Population Description

All participants in the FAS.

Arm/Group Title	Levodopa-Carbidopa Intestinal Gel (LCIG)
Arm/Group Description	All participants received LCIG via the N-J tube during the nasojejunal (N-J) Test Period and delivered to the proximal small intestine via percutaneous endoscopic gastrostomy - with jejunal extension tube (PEG-J) during the Post-PEG-J Long-Term Treatment Period. The starting dose was individually determined based on the daily dose of oral levodopa prior to study enrollment. The infusion dose was individually optimized for each participant on the basis of response and potential adverse events. During the PEG-J Period, LCIG was expected to be infused continuously over approximately 16 hours daily with a rate of infusion ranging from 1 to 10 mL/hour (20 to 200 mg of levodopa/hour).
Measure Participants	30
Baseline	16.5 (9.70)
Final PEG-J visit	14.3 (11.30)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levodopa-Carbidopa Intestinal Gel (LCIG)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.182
	Comments
	Method	One-sample t-test, 2-sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.1
	Confidence Interval	(2-Sided) 95%; -5.3 to 1.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Average Daily Normalized "On" Time With Troublesome Dyskinesia: Change From Baseline To The Final PEG-J Visit
Description	Based on the Parkinson's Disease Symptom Diary. "On" time is when PD symptoms are well controlled by the drug. "Off" time is when PD symptoms are not adequately controlled by the drug. The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic 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. Positive change from baseline for "on" time indicates improvement.
Time Frame	Baseline (end of screening period) and Final PEG-J Visit (up to week 12)

Outcome Measure Data

Analysis Population Description

All participants in the FAS with available data.

Arm/Group Title	Levodopa-Carbidopa Intestinal Gel (LCIG)
Arm/Group Description	All participants received LCIG via the N-J tube during the nasojejunal (N-J) Test Period and delivered to the proximal small intestine via percutaneous endoscopic gastrostomy - with jejunal extension tube (PEG-J) during the Post-PEG-J Long-Term Treatment Period. The starting dose was individually determined based on the daily dose of oral levodopa prior to study enrollment. The infusion dose was individually optimized for each participant on the basis of response and potential adverse events. During the PEG-J Period, LCIG was expected to be infused continuously over approximately 16 hours daily with a rate of infusion ranging from 1 to 10 mL/hour (20 to 200 mg of levodopa/hour).
Measure Participants	29
Baseline	1.12 (2.311)
Last PEG-J visit	0.12 (0.394)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levodopa-Carbidopa Intestinal Gel (LCIG)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.032
	Comments
	Method	One-sample t-test, 2-sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.00
	Confidence Interval	(2-Sided) 95%; -1.90 to -0.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Parkinson's Disease Questionnaire (PDQ-39) Mobility, Emotional Well-Being, Stigma, Social Support, Cognition, Communication, and Bodily Discomfort Domain Scores: Change From Baseline To The Final PEG-J Visit
Description	The PDQ-39 is a self-administered questionnaire which comprises 39 items (each question answered on a 5-point scale) addressing 8 domains of health in Parkinson's disease patients: Mobility (e.g., fear of falling when walking) includes 10 questions; Emotional Well-being (e.g., feelings of isolation) includes 6 questions; Stigma (e.g., social embarrassment) includes 4 questions; Social Support includes 3 questions; Cognition includes 4 questions; Communication includes 3 questions; and Bodily Discomfort includes 3 questions. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness.
Time Frame	Baseline (end of screening period) and Final PEG-J Visit (up to week 12)

Outcome Measure Data

Analysis Population Description

All participants in the FAS.

Arm/Group Title	Levodopa-Carbidopa Intestinal Gel (LCIG)
Arm/Group Description	All participants received LCIG via the N-J tube during the nasojejunal (N-J) Test Period and delivered to the proximal small intestine via percutaneous endoscopic gastrostomy - with jejunal extension tube (PEG-J) during the Post-PEG-J Long-Term Treatment Period. The starting dose was individually determined based on the daily dose of oral levodopa prior to study enrollment. The infusion dose was individually optimized for each participant on the basis of response and potential adverse events. During the PEG-J Period, LCIG was expected to be infused continuously over approximately 16 hours daily with a rate of infusion ranging from 1 to 10 mL/hour (20 to 200 mg of levodopa/hour).
Measure Participants	30
Mobility Domain-Baseline	55.7 (19.46)
Mobility Domain-Last PEG-J visit	36.5 (22.49)
Emotional Well-Being Domain-Baseline	30.8 (19.13)
Emotional Well-Being Domain-Last PEG-J visit	24.3 (18.02)
Stigma Domain-Baseline	20.6 (22.21)
Stigma Domain-Last PEG-J visit	13.1 (20.78)
Social Support Domain-Baseline	16.1 (18.69)
Social Support Domain-Last PEG-J visit	14.6 (21.35)
Cognition Domain-Baseline	28.5 (19.26)
Cognition Domain-Last PEG-J visit	14.6 (13.16)
Communication Domain-Baseline	13.3 (14.62)
Communication Domain-Last PEG-J visit	14.4 (16.94)
Bodily Discomfort Domain-Baseline	35.0 (21.60)
Bodily Discomfort Domain-Last PEG-J visit	17.2 (14.83)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levodopa-Carbidopa Intestinal Gel (LCIG)
	Comments	Mobility Domain analysis.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	One-sample t-test, 2-sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-19.2
	Confidence Interval	(2-Sided) 95%; -27.8 to -10.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Levodopa-Carbidopa Intestinal Gel (LCIG)
	Comments	Emotional Well-Being Domain analysis.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.059
	Comments
	Method	One-sample t-test, 2-sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-6.5
	Confidence Interval	(2-Sided) 95%; -13.3 to 0.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Levodopa-Carbidopa Intestinal Gel (LCIG)
	Comments	Stigma Domain analysis.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.070
	Comments
	Method	One-sample t-test, 2-sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-7.5
	Confidence Interval	(2-Sided) 95%; -15.6 to 0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Levodopa-Carbidopa Intestinal Gel (LCIG)
	Comments	Social Support Domain analysis.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.591
	Comments
	Method	One-sample t-test, 2-sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.5
	Confidence Interval	(2-Sided) 95%; -7.3 to 4.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Levodopa-Carbidopa Intestinal Gel (LCIG)
	Comments	Cognition Domain analysis.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	One-sample t-test, 2-sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-14.0
	Confidence Interval	(2-Sided) 95%; -20.7 to -7.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Levodopa-Carbidopa Intestinal Gel (LCIG)
	Comments	Communication Domain analysis.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.670
	Comments
	Method	One-sample t-test, 2-sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.1
	Confidence Interval	(2-Sided) 95%; -4.2 to 6.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Levodopa-Carbidopa Intestinal Gel (LCIG)
	Comments	Bodily Discomfort Domain analysis.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	One-sample t-test, 2-sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-17.8
	Confidence Interval	(2-Sided) 95%; -25.2 to -10.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Unified Parkinson's Disease Rating Scale (UPDRS) Total Score: Change From Baseline To The Final PEG-J Visit
Description	The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The total score is the sum of the responses to the 31 questions (44 answers) that comprise Parts I-III of the scale. The total score will range from 0 to176, with 176 representing the worst (total) disability, and 0 representing no disability.
Time Frame	Baseline and Final PEG-J Visit (up to Week 12)

Outcome Measure Data

Analysis Population Description

All participants in the FAS.

Arm/Group Title	Levodopa-Carbidopa Intestinal Gel (LCIG)
Arm/Group Description	All participants received LCIG via the N-J tube during the nasojejunal (N-J) Test Period and delivered to the proximal small intestine via percutaneous endoscopic gastrostomy - with jejunal extension tube (PEG-J) during the Post-PEG-J Long-Term Treatment Period. The starting dose was individually determined based on the daily dose of oral levodopa prior to study enrollment. The infusion dose was individually optimized for each participant on the basis of response and potential adverse events. During the PEG-J Period, LCIG was expected to be infused continuously over approximately 16 hours daily with a rate of infusion ranging from 1 to 10 mL/hour (20 to 200 mg of levodopa/hour).
Measure Participants	30
Baseline	27.7 (15.53)
Last PEG-J visit	22.9 (17.53)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levodopa-Carbidopa Intestinal Gel (LCIG)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.056
	Comments
	Method	One-sample t-test, 2-sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-4.8
	Confidence Interval	(2-Sided) 95%; -9.8 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Unified Parkinson's Disease Rating Scale (UPDRS) Part I Score: Change From Baseline To The Final PEG-J Visit
Description	The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The Part I Score is the sum of the answers to the 4 questions that comprise Part I, each of which are measured on a 5-point scale (0-4). The Part I score ranges from 0 to 16 and higher scores are associated with more disability.
Time Frame	Baseline (end of screening period) and Final PEG-J Visit (up to week 12)

Outcome Measure Data

Analysis Population Description

All participants in the FAS.

Arm/Group Title	Levodopa-Carbidopa Intestinal Gel (LCIG)
Arm/Group Description	All participants received LCIG via the N-J tube during the nasojejunal (N-J) Test Period and delivered to the proximal small intestine via percutaneous endoscopic gastrostomy - with jejunal extension tube (PEG-J) during the Post-PEG-J Long-Term Treatment Period. The starting dose was individually determined based on the daily dose of oral levodopa prior to study enrollment. The infusion dose was individually optimized for each participant on the basis of response and potential adverse events. During the PEG-J Period, LCIG was expected to be infused continuously over approximately 16 hours daily with a rate of infusion ranging from 1 to 10 mL/hour (20 to 200 mg of levodopa/hour).
Measure Participants	30
Baseline	1.8 (2.02)
Last PEG-J visit	0.9 (0.91)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levodopa-Carbidopa Intestinal Gel (LCIG)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.011
	Comments
	Method	One-sample t-test, 2-sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95%; -1.6 to -0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Unified Parkinson's Disease Rating Scale (UPDRS) Part IV Score: Change From Baseline To The Final PEG-J Visit
Description	The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The Part IV Score is the sum of the answers to the 11 questions that comprise Part IV, each of which are measured on a 5-point scale (0-4) or a 2-point scale (0 or 1). The Part IV score ranges from 0 to 23 and higher scores are associated with more disability.
Time Frame	Baseline (end of screening period) and Final PEG-J Visit (up to week 12)

Outcome Measure Data

Analysis Population Description

All participants in the FAS.

Arm/Group Title	Levodopa-Carbidopa Intestinal Gel (LCIG)
Arm/Group Description	All participants received LCIG via the N-J tube during the nasojejunal (N-J) Test Period and delivered to the proximal small intestine via percutaneous endoscopic gastrostomy - with jejunal extension tube (PEG-J) during the Post-PEG-J Long-Term Treatment Period. The starting dose was individually determined based on the daily dose of oral levodopa prior to study enrollment. The infusion dose was individually optimized for each participant on the basis of response and potential adverse events. During the PEG-J Period, LCIG was expected to be infused continuously over approximately 16 hours daily with a rate of infusion ranging from 1 to 10 mL/hour (20 to 200 mg of levodopa/hour).
Measure Participants	30
Baseline	8.7 (3.15)
Last PEG-J visit	5.5 (3.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levodopa-Carbidopa Intestinal Gel (LCIG)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	One-sample t-test, 2-sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-3.2
	Confidence Interval	(2-Sided) 95%; -4.4 to -1.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Average Daily Normalized "Off" Time Excluding Subjects Who Did Not Receive LCIG During the Entire PEG-J Period: Change From Baseline To The Final PEG-J Visit
Description	Based on the Parkinson's Disease Symptom Diary. "On" time is when PD symptoms are well controlled by the drug. "Off" time is when PD symptoms are not adequately controlled by the drug. The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic 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. Negative change from baseline for "off" time indicates improvement.
Time Frame	Baseline (end of screening period) and Final PEG-J Visit (up to week 12)

Outcome Measure Data

Analysis Population Description

All participants in the FAS with available data.

Arm/Group Title	Levodopa-Carbidopa Intestinal Gel (LCIG)
Arm/Group Description	All participants received LCIG via the N-J tube during the nasojejunal (N-J) Test Period and delivered to the proximal small intestine via percutaneous endoscopic gastrostomy - with jejunal extension tube (PEG-J) during the Post-PEG-J Long-Term Treatment Period. The starting dose was individually determined based on the daily dose of oral levodopa prior to study enrollment. The infusion dose was individually optimized for each participant on the basis of response and potential adverse events. During the PEG-J Period, LCIG was expected to be infused continuously over approximately 16 hours daily with a rate of infusion ranging from 1 to 10 mL/hour (20 to 200 mg of levodopa/hour).
Measure Participants	28
Baseline	7.32 (2.290)
Last PEG-J visit	2.67 (2.341)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levodopa-Carbidopa Intestinal Gel (LCIG)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	One-sample t-test, 2-sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-4.65
	Confidence Interval	(2-Sided) 95%; -5.83 to -3.47
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Average Daily Normalized "Off" Time Including All PD Diaries Regardless if They Were Completed After the Subject Had Used a Concomitant Anti-Parkinsonian Medication: Change From Baseline To The Final PEG-J Visit
Description	Based on the Parkinson's Disease Symptom Diary. "On" time is when PD symptoms are well controlled by the drug. "Off" time is when PD symptoms are not adequately controlled by the drug. The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic 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. Negative change from baseline for "off" time indicates improvement.
Time Frame	Baseline (end of screening period) and Final PEG-J Visit (up to week 12)

Outcome Measure Data

Analysis Population Description

All participants in the FAS with available data.

Arm/Group Title	Levodopa-Carbidopa Intestinal Gel (LCIG)
Arm/Group Description	All participants received LCIG via the N-J tube during the nasojejunal (N-J) Test Period and delivered to the proximal small intestine via percutaneous endoscopic gastrostomy - with jejunal extension tube (PEG-J) during the Post-PEG-J Long-Term Treatment Period. The starting dose was individually determined based on the daily dose of oral levodopa prior to study enrollment. The infusion dose was individually optimized for each participant on the basis of response and potential adverse events. During the PEG-J Period, LCIG was expected to be infused continuously over approximately 16 hours daily with a rate of infusion ranging from 1 to 10 mL/hour (20 to 200 mg of levodopa/hour).
Measure Participants	29
Baseline	7.37 (2.263)
Last PEG-J visit	2.78 (2.382)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levodopa-Carbidopa Intestinal Gel (LCIG)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	One-sample t-test, 2-sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-4.58
	Confidence Interval	(2-Sided) 95%; -5.73 to -3.44
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

Title	Average Daily Normalized "Off" Time at Baseline and Each Visit: Change From Baseline To The Final PEG-J Visit
Description	Based on the Parkinson's Disease Symptom Diary. "On" time is when PD symptoms are well controlled by the drug. "Off" time is when PD symptoms are not adequately controlled by the drug. The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic 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. n= the number of participants with available data at each time point.
Time Frame	Baseline (end of screening period) and Weeks 2, 4, 6, 8, 10, and 12

Outcome Measure Data

Analysis Population Description

All participants in the FAS with available data.

Arm/Group Title	Levodopa-Carbidopa Intestinal Gel (LCIG)
Arm/Group Description	All participants received LCIG via the N-J tube during the nasojejunal (N-J) Test Period and delivered to the proximal small intestine via percutaneous endoscopic gastrostomy - with jejunal extension tube (PEG-J) during the Post-PEG-J Long-Term Treatment Period. The starting dose was individually determined based on the daily dose of oral levodopa prior to study enrollment. The infusion dose was individually optimized for each participant on the basis of response and potential adverse events. During the PEG-J Period, LCIG was expected to be infused continuously over approximately 16 hours daily with a rate of infusion ranging from 1 to 10 mL/hour (20 to 200 mg of levodopa/hour).
Measure Participants	29
Baseline (n=29)	7.37 (2.263)
Week 2 (n=29)	3.17 (2.365)
Week 4 (n=29)	3.68 (3.077)
Week 6 (n=29)	2.61 (2.318)
Week 8 (n=27)	2.77 (2.324)
Week 10 (n=27)	2.47 (2.210)
Week 12 (n=27)	2.45 (2.094)

16. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Description	An adverse event (AE) is any untoward medical occurrence in a participant which does not necessarily have a causal relationship with this treatment. A serious AE (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent AEs (TEAEs) are defined as any event that began or worsened in severity after N-J placement. The investigator assessed the relationship of each event to the use of study drug as Reasonable Possibility or No Reasonable Possibility. For more details on adverse events please see the AE section below.
Time Frame	From N-J placement to the end of study or early termination of treatment, including the removal of PEG-J (up to 17 weeks), plus 30 days.

Outcome Measure Data

Analysis Population Description

Safety Analysis Set: All subjects who had undergone the N-J placement procedure.

Arm/Group Title	Levodopa-Carbidopa Intestinal Gel (LCIG)
Arm/Group Description	All participants received LCIG via the N-J tube during the nasojejunal (N-J) Test Period and delivered to the proximal small intestine via percutaneous endoscopic gastrostomy - with jejunal extension tube (PEG-J) during the Post-PEG-J Long-Term Treatment Period. The starting dose was individually determined based on the daily dose of oral levodopa prior to study enrollment. The infusion dose was individually optimized for each participant on the basis of response and potential adverse events. During the PEG-J Period, LCIG was expected to be infused continuously over approximately 16 hours daily with a rate of infusion ranging from 1 to 10 mL/hour (20 to 200 mg of levodopa/hour).
Measure Participants	31
Any TEAE	31 100%
Any TEAE at least possibly related to LCIG	0 0%
Any TEAE at least possibly related to LCIG System	30 96.8%
Any severe TEAE	2 6.5%
Any SAE	4 12.9%
Any TEAE Leading to Discontinuation of Study	1 3.2%
Death	1 3.2%
Death related to AE	1 3.2%

17. Secondary Outcome

Title	Number of Participants With Potentially Clinically Significant Vital Sign Parameters
Description	Terms abbreviated in the table include supine systolic blood pressure (SuSBP), standing systolic blood pressure (StSBP), orthostatic systolic blood pressure (OSBP), supine diastolic blood pressure (SuDBP), standing diastolic blood pressure (StDBP), orthostatic diastolic blood pressure (ODBP), supine pulse (SuP) in beats per minute (bpm), standing pulse (StP), body temperature (Temp), and baseline (BL). Increase and decrease are signified by ↑ and ↓, respectively.
Time Frame	From Baseline (end of screening period) to Final PEG-J Visit (up to week 12)

Outcome Measure Data

Analysis Population Description

Safety analysis set.

Arm/Group Title	Levodopa-Carbidopa Intestinal Gel (LCIG)
Arm/Group Description	All participants received LCIG via the N-J tube during the nasojejunal (N-J) Test Period and delivered to the proximal small intestine via percutaneous endoscopic gastrostomy - with jejunal extension tube (PEG-J) during the Post-PEG-J Long-Term Treatment Period. The starting dose was individually determined based on the daily dose of oral levodopa prior to study enrollment. The infusion dose was individually optimized for each participant on the basis of response and potential adverse events. During the PEG-J Period, LCIG was expected to be infused continuously over approximately 16 hours daily with a rate of infusion ranging from 1 to 10 mL/hour (20 to 200 mg of levodopa/hour).
Measure Participants	31
SuSBP <=90 and >30 mm Hg ↓ from BL	3 9.7%
SuSBP >=180 and >40 mm Hg ↑ from BL	1 3.2%
StSBP <=90 and >30 mm Hg ↓ from BL	3 9.7%
StSBP >=180 and >40 mm Hg ↑ from BL	1 3.2%
OSBP: ↓ >=30 mm Hg Supine to Standing	8 25.8%
SuDBP <=50 and >30 mm Hg ↓ from BL	1 3.2%
SuDBP >=105 and >30 mm Hg ↑ from BL	1 3.2%
StDBP <=50 and >30 mm Hg ↓ from BL	3 9.7%
StDBP >=105 and >30 mm Hg ↑ from BL	3 9.7%
ODBP: ↓ >=20 mm Hg Supine to Standing	11 35.5%
SuP <=50 and >30 bpm ↓ from BL	0 0%
SuP >=120 and >30 bpm ↑ from BL	0 0%
StP <=50 and >30 bpm ↓ from BL	0 0%
StP >=120 and >30 bpm ↑ from BL	0 0%
Weight <=7% ↓ from BL	8 25.8%
Weight >=7% ↑ from BL	2 6.5%

18. Secondary Outcome

Title	Number of Participants With Potentially Clinically Significant Values for Hematology Parameters
Description	Terms abbreviated in the table include females (f), males (m), and femtoliters (fL).
Time Frame	From Baseline (end of screening period) to Final PEG-J Visit (up to week 12)

Outcome Measure Data

Analysis Population Description

Safety analysis set.

Arm/Group Title	Levodopa-Carbidopa Intestinal Gel (LCIG)
Arm/Group Description	All participants received LCIG via the N-J tube during the nasojejunal (N-J) Test Period and delivered to the proximal small intestine via percutaneous endoscopic gastrostomy - with jejunal extension tube (PEG-J) during the Post-PEG-J Long-Term Treatment Period. The starting dose was individually determined based on the daily dose of oral levodopa prior to study enrollment. The infusion dose was individually optimized for each participant on the basis of response and potential adverse events. During the PEG-J Period, LCIG was expected to be infused continuously over approximately 16 hours daily with a rate of infusion ranging from 1 to 10 mL/hour (20 to 200 mg of levodopa/hour).
Measure Participants	31
Haemoglobin <90 g/L (f); <100 g/L (m)	1 3.2%
Haematocrit <30% (f); <34% (m)	2 6.5%
Red Blood Cells <2.0 10^12/L (f); <2.5 10^12/L (m)	0 0%
Platelet Count <95 10^9/L	1 3.2%
Platelet Count >700 10^9/L	0 0%
White Blood Cells <2.8 10^9/L	0 0%
White Blood Cells >16.0 10^9/L	1 3.2%
Lymphocytes >80%	0 0%
Monocytes >30%	0 0%
Eosinophils >10%	1 3.2%
Mean Corpuscular Volume <60 fL	0 0%
Mean Corpuscular Volume >120 fL	0 0%

19. Secondary Outcome

Title	Number of Participants With Potentially Clinically Significant Values for Clinical Chemistry Parameters
Description	Terms abbreviated in the table include upper limit of normal (ULN), male (m), and female (f).
Time Frame	From Baseline (end of screening period) to Final PEG-J Visit (up to week 12)

Outcome Measure Data

Analysis Population Description

Safety analysis set.

Arm/Group Title	Levodopa-Carbidopa Intestinal Gel (LCIG)
Arm/Group Description	All participants received LCIG via the N-J tube during the nasojejunal (N-J) Test Period and delivered to the proximal small intestine via percutaneous endoscopic gastrostomy - with jejunal extension tube (PEG-J) during the Post-PEG-J Long-Term Treatment Period. The starting dose was individually determined based on the daily dose of oral levodopa prior to study enrollment. The infusion dose was individually optimized for each participant on the basis of response and potential adverse events. During the PEG-J Period, LCIG was expected to be infused continuously over approximately 16 hours daily with a rate of infusion ranging from 1 to 10 mL/hour (20 to 200 mg of levodopa/hour).
Measure Participants	31
Alanine Aminotransferase >3xULN	1 3.2%
Aspartate Aminotransferase >3xULN	1 3.2%
Gamma-glutamyl Transferase >3x ULN	0 0%
Alkaline Phosphatase >400 U/L	0 0%
Total Bilirubin >2xULN	0 0%
Creatine Phosphokinase >3x ULN	0 0%
Creatinine >177 µmol/L	0 0%
Blood Urea Nitrogen >10.8 mmol/L	2 6.5%
Uric Acid>500µmol/L(f);>590µmol/L(m)	0 0%
Calcium <1.75 mmol/L	0 0%
Calcium >3.0 mmol/L	0 0%
Sodium <126 mmol/L	0 0%
Sodium >156 mmol/L	0 0%
Potassium <3.0 mmol/L	1 3.2%
Potassium >6.0 mmol/L	0 0%
Non-fasting Glucose <2.78 mmol/L	1 3.2%
Non-fasting Glucose >16.0 mmol/L	1 3.2%
Albumin <25 g/L	1 3.2%
Albumin >70 g/L	0 0%
Total Protein <45 g/L	0 0%
Cholesterol >12.9 mmol/L	0 0%
Triglycerides >5.6 mmol/L	0 0%
Lactate dehydrogenase >3x ULN	0 0%

20. Secondary Outcome

Title	Number of Participants With Potentially Clinically Significant Values for 12-lead Electrocardiogram (ECG)
Description	Terms abbreviated in the table include heart rate (HR) in beats per minute (bpm), PR interval (PRI), QT interval corrected for heart rate using Bazett's formula (QTcB), QT interval corrected for heart rate using Fridericia's formula (QTcF), and baseline (BL). Increase and decrease are signified by ↑ and ↓, respectively. n = the number of participants with available data at each time point.
Time Frame	From Baseline (end of screening period) to Final PEG-J Visit (up to week 12)

Outcome Measure Data

Analysis Population Description

Safety analysis set.

Arm/Group Title	Levodopa-Carbidopa Intestinal Gel (LCIG)
Arm/Group Description	All participants received LCIG via the N-J tube during the nasojejunal (N-J) Test Period and delivered to the proximal small intestine via percutaneous endoscopic gastrostomy - with jejunal extension tube (PEG-J) during the Post-PEG-J Long-Term Treatment Period. The starting dose was individually determined based on the daily dose of oral levodopa prior to study enrollment. The infusion dose was individually optimized for each participant on the basis of response and potential adverse events. During the PEG-J Period, LCIG was expected to be infused continuously over approximately 16 hours daily with a rate of infusion ranging from 1 to 10 mL/hour (20 to 200 mg of levodopa/hour).
Measure Participants	31
HR <=50 and >30 bpm ↓ from BL (n=31)	0 0%
HR >=120 and >30 bpm ↑ from BL (n=31)	0 0%
PR Interval <120 msec (n=30)	0 0%
PR Interval >220 msec (n=30)	1 3.2%
QTcB Interval >480 msec (n=31)	1 3.2%
QTcB Interval >60 msec ↑ from BL (n=31)	1 3.2%
QTcF Interval >480 msec (n=31)	0 0%
QTcF Interval >60 msec ↑ from BL (n=31)	1 3.2%

21. Other Pre-specified Outcome

Title	Neurological Examination
Description	Any abnormal findings are recorded as an adverse event after the first study drug administration; please see the AE section below. Further analysis for neurological examination findings was not performed per protocol.
Time Frame	From Baseline (end of screening period) to Final PEG-J Visit (up to week 12)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

22. Other Pre-specified Outcome

Title	Physical Examination
Description	Any abnormal findings are recorded as an adverse event after the first study drug administration; please see the AE section below. Further analysis for physical examination findings was not performed per protocol.
Time Frame	From Baseline (end of screening period) to Final PEG-J Visit (up to week 12)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	From study enrollment to the end of study or early termination of treatment, including the removal of PEG-J (up to 17 weeks), plus 30 days.
Adverse Event Reporting Description	Serious AEs and treatment-emergent AEs are presented. Treatment-emergent AEs were defined as AEs that began or worsened from date of the N-J placement to 30 days after device removal or until the first dose of extension study drug for those who chose to continue LCIG treatment.
Arm/Group Title	Levodopa-Carbidopa Intestinal Gel (LCIG)
Arm/Group Description	All participants received LCIG via the N-J tube during the nasojejunal (N-J) Test Period and delivered to the proximal small intestine via percutaneous endoscopic gastrostomy - with jejunal extension tube (PEG-J) during the Post-PEG-J Long-Term Treatment Period. The starting dose was individually determined based on the daily dose of oral levodopa prior to study enrollment. The infusion dose was individually optimized for each participant on the basis of response and potential adverse events. During the PEG-J Period, LCIG was expected to be infused continuously over approximately 16 hours daily with a rate of infusion ranging from 1 to 10 mL/hour (20 to 200 mg of levodopa/hour).
All Cause Mortality
	Levodopa-Carbidopa Intestinal Gel (LCIG)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Levodopa-Carbidopa Intestinal Gel (LCIG)
	Affected / at Risk (%)	# Events
Total	4/31 (12.9%)
Blood and lymphatic system disorders
DISSEMINATED INTRAVASCULAR COAGULATION	1/31 (3.2%)
Gastrointestinal disorders
ABDOMINAL PAIN	1/31 (3.2%)
CONSTIPATION	1/31 (3.2%)
GASTROINTESTINAL PERFORATION	1/31 (3.2%)
MELAENA	1/31 (3.2%)
General disorders
DEVICE DISLOCATION	1/31 (3.2%)
DEVICE KINK	1/31 (3.2%)
Infections and infestations
SEPSIS	1/31 (3.2%)
Injury, poisoning and procedural complications
FEMUR FRACTURE	1/31 (3.2%)
Respiratory, thoracic and mediastinal disorders
PNEUMONIA ASPIRATION	2/31 (6.5%)
Other (Not Including Serious) Adverse Events
	Levodopa-Carbidopa Intestinal Gel (LCIG)
	Affected / at Risk (%)	# Events
Total	31/31 (100%)
Blood and lymphatic system disorders
ANAEMIA	3/31 (9.7%)
Cardiac disorders
CARDIAC VALVE DISEASE	1/31 (3.2%)
PALPITATIONS	1/31 (3.2%)
Eye disorders
VITREOUS FLOATERS	1/31 (3.2%)
Gastrointestinal disorders
ABDOMINAL DISCOMFORT	1/31 (3.2%)
ABDOMINAL DISTENSION	2/31 (6.5%)
ABDOMINAL PAIN	1/31 (3.2%)
ABDOMINAL PAIN UPPER	2/31 (6.5%)
CONSTIPATION	6/31 (19.4%)
DENTAL CARIES	1/31 (3.2%)
DIARRHOEA	6/31 (19.4%)
DRY MOUTH	1/31 (3.2%)
GASTRIC ULCER	1/31 (3.2%)
GASTROOESOPHAGEAL REFLUX DISEASE	1/31 (3.2%)
ILEUS	1/31 (3.2%)
NAUSEA	1/31 (3.2%)
PNEUMOPERITONEUM	1/31 (3.2%)
STOMATITIS	1/31 (3.2%)
TOOTHACHE	2/31 (6.5%)
General disorders
CATHETER SITE PAIN	1/31 (3.2%)
CATHETER SITE PRURITUS	1/31 (3.2%)
CHEST DISCOMFORT	1/31 (3.2%)
CHEST PAIN	1/31 (3.2%)
COMPLICATION OF DEVICE INSERTION	2/31 (6.5%)
PYREXIA	2/31 (6.5%)
Infections and infestations
ALVEOLAR OSTEITIS	1/31 (3.2%)
BODY TINEA	1/31 (3.2%)
CATHETER SITE INFECTION	1/31 (3.2%)
INCISION SITE CELLULITIS	1/31 (3.2%)
INCISION SITE INFECTION	1/31 (3.2%)
NASOPHARYNGITIS	6/31 (19.4%)
RHINITIS	1/31 (3.2%)
SIALOADENITIS	1/31 (3.2%)
STOMA SITE CELLULITIS	1/31 (3.2%)
STOMA SITE INFECTION	2/31 (6.5%)
TINEA PEDIS	3/31 (9.7%)
Injury, poisoning and procedural complications
CONTUSION	1/31 (3.2%)
FALL	6/31 (19.4%)
INCISION SITE DERMATITIS	1/31 (3.2%)
INCISION SITE ERYTHEMA	4/31 (12.9%)
INCISION SITE PAIN	13/31 (41.9%)
INCISION SITE RASH	2/31 (6.5%)
LACERATION	1/31 (3.2%)
POSTOPERATIVE ILEUS	1/31 (3.2%)
PROCEDURAL PAIN	5/31 (16.1%)
RIB FRACTURE	1/31 (3.2%)
SCRATCH	1/31 (3.2%)
SKIN ABRASION	1/31 (3.2%)
STOMA SITE ERYTHEMA	1/31 (3.2%)
SUTURE RELATED COMPLICATION	2/31 (6.5%)
TOOTH FRACTURE	1/31 (3.2%)
WOUND COMPLICATION	1/31 (3.2%)
Investigations
BLOOD GLUCOSE INCREASED	1/31 (3.2%)
BLOOD HOMOCYSTEINE INCREASED	5/31 (16.1%)
BLOOD PRESSURE DECREASED	2/31 (6.5%)
BLOOD PRESSURE INCREASED	1/31 (3.2%)
BLOOD TRIGLYCERIDES INCREASED	1/31 (3.2%)
WEIGHT DECREASED	2/31 (6.5%)
Metabolism and nutrition disorders
DECREASED APPETITE	1/31 (3.2%)
DIABETES MELLITUS	1/31 (3.2%)
HYPONATRAEMIA	1/31 (3.2%)
MALNUTRITION	1/31 (3.2%)
Musculoskeletal and connective tissue disorders
BACK PAIN	1/31 (3.2%)
FOOT DEFORMITY	1/31 (3.2%)
LUMBAR SPINAL STENOSIS	1/31 (3.2%)
MUSCULOSKELETAL CHEST PAIN	1/31 (3.2%)
MUSCULOSKELETAL PAIN	2/31 (6.5%)
MYALGIA	1/31 (3.2%)
PAIN IN EXTREMITY	1/31 (3.2%)
POSTURE ABNORMAL	1/31 (3.2%)
Nervous system disorders
CARPAL TUNNEL SYNDROME	1/31 (3.2%)
CEREBRAL INFARCTION	1/31 (3.2%)
DYSKINESIA	5/31 (16.1%)
DYSTONIA	1/31 (3.2%)
HEADACHE	2/31 (6.5%)
METABOLIC ENCEPHALOPATHY	1/31 (3.2%)
MIGRAINE	1/31 (3.2%)
RADICULOPATHY	1/31 (3.2%)
RESTLESS LEGS SYNDROME	1/31 (3.2%)
Psychiatric disorders
AGITATION	1/31 (3.2%)
ANXIETY	3/31 (9.7%)
HEAD BANGING	1/31 (3.2%)
ILLUSION	1/31 (3.2%)
INSOMNIA	2/31 (6.5%)
NIGHTMARE	1/31 (3.2%)
Renal and urinary disorders
DYSURIA	1/31 (3.2%)
Respiratory, thoracic and mediastinal disorders
DYSPNOEA	1/31 (3.2%)
EPISTAXIS	2/31 (6.5%)
OROPHARYNGEAL PAIN	2/31 (6.5%)
PRODUCTIVE COUGH	1/31 (3.2%)
RHINORRHOEA	1/31 (3.2%)
Skin and subcutaneous tissue disorders
ACNE	1/31 (3.2%)
DERMATITIS CONTACT	1/31 (3.2%)
DRY SKIN	1/31 (3.2%)
ECZEMA	2/31 (6.5%)
EXCESSIVE GRANULATION TISSUE	10/31 (32.3%)
HYPERHIDROSIS	1/31 (3.2%)
PETECHIAE	1/31 (3.2%)
PRURITUS	2/31 (6.5%)
PRURITUS GENERALISED	1/31 (3.2%)
SKIN ULCER	1/31 (3.2%)
Vascular disorders
HYPERTENSION	1/31 (3.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.