Levodopa-Carbidopa Intestinal Gel Open-Label Study in Advanced Parkinson's Disease

An Open-Label, 12-Month Safety and Efficacy Study of Levodopa - Carbidopa Intestinal Gel in Levodopa-Responsive Subjects With Advanced Parkinson's Disease and Severe Motor Fluctuations Despite Optimized Treatment With Available Parkinson's Disease Medications

The primary objective of this study will be to provide further evidence of the long-term safety and tolerability of levodopa-carbidopa intestinal gel (Duodopa®) over 12-months in participants with advanced Parkinson's disease (PD) and severe motor fluctuations.

Study Overview

• Status: Completed
• Conditions: Advanced Parkinson's Disease
• Intervention / Treatment: Device: CADD-Legacy® 1400 ambulatory infusion pump; Device: PEG tube; Device: J-tube; Drug: Levodopa-carbidopa intestinal gel

Detailed Description

The study was composed of a screening period followed by 3 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 (NJ) tube placement.
• NJ Test Period (2 to 14 days): first hospitalization period, Baseline assessments, placement of NJ tube, and optimization of levodopa-carbidopa intestinal gel (LCIG) treatment via NJ tube and infusion pump (participant was hospitalized for NJ tube placement but hospitalization was not required for entire duration of LCIG treatment optimization).
• PEG-J Period (2 to 14 days): second hospitalization period; placement of PEG-J tube; further optimization of LCIG treatment.
• Post PEG-J Long-Term Treatment Period (Day 28 to Day 378): LCIG administration via a permanent PEG-J tube and infusion pump, with dosage adjusted according to clinical condition.

• Study Type: Interventional
• Enrollment (Actual): 354
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia, 5000
    • Site Reference ID/Investigator# 46429
  • Heidelberg, Australia, 3084
    • Site Reference ID/Investigator# 46427
  • Westmead, Australia, 2145
    • Site Reference ID/Investigator# 46425
• Canada
  • Edmonton, Canada, T6G 2B7
    • Site Reference ID/Investigator# 54545
  • Montreal, Canada, H2L 4M1
    • Site Reference ID/Investigator# 46433
  • Toronto, Canada, M5T 2S8
    • Site Reference ID/Investigator# 46434
• Czech Republic
  • Brno, Czech Republic, 65691
    • Site Reference ID/Investigator# 46436
  • Hradec Kralove, Czech Republic, 500 05
    • Site Reference ID/Investigator# 46438
  • Pardubice, Czech Republic, 532 03
    • Site Reference ID/Investigator# 46435
  • Prague 2, Czech Republic, 128 08
    • Site Reference ID/Investigator# 46437
  • Prague 5, Czech Republic, 15006
    • Site Reference ID/Investigator# 46439
• Finland
  • Lahti, Finland, 15850
    • Site Reference ID/Investigator# 48003
• Germany
  • Berlin, Germany, 12200
    • Site Reference ID/Investigator# 48028
  • Berlin, Germany, 13088
    • Site Reference ID/Investigator# 48029
  • Freiburg, Germany, 79106
    • Site Reference ID/Investigator# 48036
  • Goettingen, Germany, 37075
    • Site Reference ID/Investigator# 48034
  • Hanau, Germany, 63450
    • Site Reference ID/Investigator# 48022
  • Hanover, Germany, 30625
    • Site Reference ID/Investigator# 48024
  • Mainz, Germany, 55131
    • Site Reference ID/Investigator# 48035
• Israel
  • Tel Aviv, Israel, 64239
    • Site Reference ID/Investigator# 49882
• Italy
  • Arcugnano, Italy, 36057
    • Site Reference ID/Investigator# 50131
  • Catania, Italy, 95125
    • Site Reference ID/Investigator# 50132
  • Genoa, Italy, 16132
    • Site Reference ID/Investigator# 50128
  • Lido di Camaiore, Italy, 55043
    • Site Reference ID/Investigator# 50129
  • Naples, Italy, 80131
    • Site Reference ID/Investigator# 50130
  • Rome, Italy, 00163
    • Site Reference ID/Investigator# 50127
• Netherlands
  • Nijmegen, Netherlands, 6532 SZ
    • Site Reference ID/Investigator# 50138
• New Zealand
  • Auckland, New Zealand, 1010
    • Site Reference ID/Investigator# 50126
  • Christchurch, New Zealand, 8011
    • Site Reference ID/Investigator# 50123
  • Hamilton, New Zealand, 3204
    • Site Reference ID/Investigator# 50124
  • Wellington, New Zealand, 6002
    • Site Reference ID/Investigator# 50125
• Poland
  • Lodz, Poland, 93-113
    • Site Reference ID/Investigator# 50140
  • Poznan, Poland, 61-485
    • Site Reference ID/Investigator# 50139
• Portugal
  • Almada, Portugal, 2805-267
    • Site Reference ID/Investigator# 50136
  • Coimbra, Portugal, 3000-075
    • Site Reference ID/Investigator# 50134
  • Lisbon, Portugal, 1649-035
    • Site Reference ID/Investigator# 50135
  • Porto, Portugal, 4200-319
    • Site Reference ID/Investigator# 50137
• Russian Federation
  • Kazan, Russian Federation, 420061
    • Site Reference ID/Investigator# 50143
  • Moscow, Russian Federation, 125367
    • Site Reference ID/Investigator# 50141
  • St. Petersburg, Russian Federation, 193312
    • Site Reference ID/Investigator# 50145
  • St. Petersburg, Russian Federation, 194044
    • Site Reference ID/Investigator# 50142
  • St. Petersburg, Russian Federation, 197089
    • Site Reference ID/Investigator# 50147
  • St. Petersburg, Russian Federation, 197706
    • Site Reference ID/Investigator# 50146
• Spain
  • Barcelona, Spain, 08003
    • Site Reference ID/Investigator# 50154
  • Barcelona, Spain, 08025
    • Site Reference ID/Investigator# 50152
  • Barcelona, Spain, 08035
    • Site Reference ID/Investigator# 50202
  • Barcelona, Spain, 08036
    • Site Reference ID/Investigator# 50155
  • Madrid, Spain, 28034
    • Site Reference ID/Investigator# 50153
• Thailand
  • Bangkok, Thailand, 10330
    • Site Reference ID/Investigator# 50150
  • Bangkok, Thailand, 10700
    • Site Reference ID/Investigator# 50151
• United Kingdom
  • Liverpool, United Kingdom, L9 7LJ
    • Site Reference ID/Investigator# 50149
  • London, United Kingdom, WC1N 3BG
    • Site Reference ID/Investigator# 50148
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35222
      • Site Reference ID/Investigator# 50065
  • California
    • Fountain Valley, California, United States, 92708
      • Site Reference ID/Investigator# 50059
    • Los Angeles, California, United States, 90033
      • Site Reference ID/Investigator# 50048
    • Oceanside, California, United States, 92056
      • Site Reference ID/Investigator# 50076
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Site Reference ID/Investigator# 50061
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Site Reference ID/Investigator# 50079
  • Florida
    • Bradenton, Florida, United States, 34205
      • Site Reference ID/Investigator# 50077
    • Fort Lauderdale, Florida, United States, 33308
      • Site Reference ID/Investigator# 50060
    • Gainesville, Florida, United States, 32610
      • Site Reference ID/Investigator# 50049
    • Jacksonville, Florida, United States, 32209
      • Site Reference ID/Investigator# 50047
    • Port Charlotte, Florida, United States, 33890
      • Site Reference ID/Investigator# 50068
    • Tampa, Florida, United States, 33613
      • Site Reference ID/Investigator# 50046
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Site Reference ID/Investigator# 50062
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Site Reference ID/Investigator# 50050
    • Chicago, Illinois, United States, 60612
      • Site Reference ID/Investigator# 50078
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Site Reference ID/Investigator# 50064
  • Louisiana
    • Shreveport, Louisiana, United States, 71103
      • Site Reference ID/Investigator# 50075
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Site Reference ID/Investigator# 50080
    • Baltimore, Maryland, United States, 21287
      • Site Reference ID/Investigator# 50074
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Site Reference ID/Investigator# 50073
  • Nebraska
    • Omaha, Nebraska, United States, 68198-2045
      • Site Reference ID/Investigator# 50042
  • New York
    • Manhasset, New York, United States, 11030
      • Site Reference ID/Investigator# 50072
    • New York, New York, United States, 10029
      • Site Reference ID/Investigator# 50067
    • New York, New York, United States, 10032
      • Site Reference ID/Investigator# 50066
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • Site Reference ID/Investigator# 50069
    • Winston-Salem, North Carolina, United States, 27157
      • Site Reference ID/Investigator# 50063
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Site Reference ID/Investigator# 50043
    • Cleveland, Ohio, United States, 44195-0001
      • Site Reference ID/Investigator# 50044
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Site Reference ID/Investigator# 50058
  • Washington
    • Kirkland, Washington, United States, 98034
      • Site Reference ID/Investigator# 50045
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Site Reference ID/Investigator# 50070

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Idiopathic Parkinson's disease (PD) according to United Kingdom Parkinson's Disease Society (UKPDS) Brain Bank Criteria
• Levodopa-responsive with severe motor fluctuations
• Recognizable off and on state (motor fluctuations) confirmed by diary

Exclusion Criteria:

• Diagnosis is unclear or a suspicion of other parkinsonian syndromes exists such as secondary parkinsonism
• Undergone surgery for the treatment of PD
• Contraindications to levodopa (such as narrow angle glaucoma)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Levodopa-Carbidopa Intestinal Gel (LCIG); All participants were to receive LCIG, via the NJ tube during the nasojejunal (NJ) 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 Post-PEG-J Long-Term Treatment 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), in most instances.

Device: CADD-Legacy® 1400 ambulatory infusion pump; Device: PEG tube; percutaneous endoscopic gastrostomy tube; Device: J-tube; jejunal tube; Drug: Levodopa-carbidopa intestinal gel; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Discontinuations Due to AEs	AE=any untoward medical occurrence which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that: results in death; is life-threatening (an event in which the subject was at risk of death at the time of the event); requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or other important medical events. Treatment-emergent events (TEAE or TESAE)=those starting after the first dose of study drug. Severe=severity reported as 'severe' or missing. Possibly or Probably Treatment Related=drug-event relationship reported as 'possible', 'probable' or missing. Death=a fatal outcome of an SAE or AE.	Screening through Day 378 + 30 days
Number of Participants With Device Complications During the Nasojejunal (NJ) Test Period	Complications of the infusion device were collected during the NJ Test period. Pump, intestinal tube, NJ tube, and other complications included (but were not limited to) device breakage, device leakage, device malfunction, device misuse, device occlusion, intentional and unintentional device removal by participant, complication of device insertion, device dislocation, device breakage, device dislocation, and post-procedural hemorrhage.	NJ Test Period (from 2 to 14 days)
Number of Participants With Device Complications During the Percutaneous Endoscopic Gastrostomy - With Jejunal Extension Tube (PEG-J) Surgery and Post-PEG Long Term Treatment Periods	Complications of the infusion device were collected during the PEG-J Surgery and Post-PEG Long-Term Treatment periods. Pump, PEG-J, stoma, and other complications included (but were not limited to) device breakage, device leakage, device malfunction, device misuse, device occlusion, intentional and unintentional device removal by participant, complication of device insertion, device dislocation, device breakage, device dislocation, and post-procedural hemorrhage.	PEG-J Surgery Period (from 2 to 14 days) through the Long Term Treatment Period (Day 28 to Day 378)
Number of Participants With Potentially Clinically Significant Values for Hematology Parameters	Potentially clinically significant values for red blood cells (RBCs), hemoglobin, and hematocrit are specified for females (f) and males (m) separately in the category rows.	Screening through Day 378
Number of Participants With Potentially Clinically Significant Values for Clinical Chemistry Parameters	Terms abbreviated in the table include aspartate aminotransferase (AST), upper limit of normal (ULN), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), female (f), and male (m).	Screening through Day 378
Number of Participants With Potentially Clinically Significant Vital Sign Parameters	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), and body temperature (Temp). Increase and decrease are signified by ↑ and ↓, respectively.	up to 56 weeks
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Parameters	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), and QT interval corrected for heart rate using Fridericia's formula (QTcF). Increase and decrease are signified by ↑ and ↓, respectively.	Screening through Day 378
Number of Participants With Sleep Attacks at Baseline	To prospectively monitor for the possible development of sleep attacks, participants were asked if they had experienced any events in which they fell asleep suddenly or unexpectedly, including while engaged in some activity (e.g., eating/drinking, speaking, or driving) or at rest, with or without any previous warning of sleepiness. Those participants who reported 1 or more sleep attacks were asked to report the number of sleep attacks they experienced, whether they experienced sleepiness or drowsiness prior to the sleep attack, whether they experienced a 'bad' outcome or problem due to a sleep attack, and if so, how many 'bad' outcomes or problems they experienced.	Baseline
Number of Participants With Sleep Attacks During the Post-PEG Long-Term Treatment Period	To prospectively monitor for the possible development of sleep attacks, participants were asked if they had experienced any events in which they fell asleep suddenly or unexpectedly, including while engaged in some activity (e.g., eating/drinking, speaking, or driving) or at rest, with or without any previous warning of sleepiness. Those participants who reported 1 or more sleep attacks were asked to report the number of sleep attacks they experienced, whether they experienced sleepiness or drowsiness prior to the sleep attack, whether they experienced a 'bad' outcome or problem due to a sleep attack, and if so, how many 'bad' outcomes or problems they experienced.	During the Post-PEG Long-Term Treatment Period (Day 28 through Day 378)
Summary of Minnesota Impulsive Disorder Interview (MIDI) Assessment of Intense Impulsive Behavior at Baseline (BL) and During the Post-PEG Long-term Treatment (PPLT) Period	The MIDI is a validated assessment of impulsive behavior consisting of a semistructured clinical interview assessing pathological gambling, trichotillomania (compulsive hair-pulling), kleptomania (compulsive stealing), pyromania (compulsive fire setting), intermittent explosive disorder, compulsive buying, and compulsive sexual behavior.	Baseline, during the Post-PEG Long-term Treatment Period (Day 28 through Day 378)
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score at Endpoint	The AIMS is an investigator-completed rating scale that has a total of 12 items rating involuntary movements of various areas of the participant's body. Items 1 through 10 are rated on a 5-point scale of severity from 0 (none), 1 (minimal), 2 (mild), 3 (moderate), to 4 (severe), and items 11 and 12 are yes/no questions regarding issues with teeth or dentures. The total AIMS score was calculated by summing items 1-10, with a possible range of 0-40; a negative change indicates improvement. The AIMS was to be performed at consistent times, when the subject was experiencing his/her worst "On" time (dyskinesia [involuntary muscle movement]).	Baseline, Endpoint (last Post-PEG Long-Term Period visit up to Day 378)
Number of Participants With Confirmed Cases of Melanoma	A comprehensive assessment for the presence of melanoma was performed during the screening period and at early termination or end of study by a dermatologist experienced with the diagnosis of the condition. If a suspicious lesion was present, a biopsy was obtained for proper diagnosis.	Screening up to Day 378
Number of Participants Taking at Least 1 Concomitant Medication During the Study	Concomitant medications include those started on or after the first open-label LCIG infusion as well as medications started prior to the first open-label infusion but continued during the study.	Screening up to Day 378

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Average Daily "Off" Time at Endpoint	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.	Baseline, Endpoint (last post-baseline visit up to Day 378)
Change From Baseline in Average Daily Normalized "On" Time With Troublesome Dyskinesia at Endpoint	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.	Baseline, Endpoint (last post-baseline visit up to Day 378)
Change From Baseline in Average Daily "On" Time Without Troublesome Dyskinesia at Endpoint	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. "On" time without troublesome dyskinesia (involuntary muscle movement) is defined as "on" time without dyskinesia and "on" time with non-troublesome dyskinesia. 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 without troublesome dyskinesia indicates improvement.	Baseline, Endpoint (last post-baseline visit up to Day 378)
Clinical Global Impression - Status (CGI-S) Score at Baseline and Clinical Global Impression - Improvement (CGI-I) Score at Endpoint	The CGI-S is a global assessment by the Investigator of current symptomatology and impact of illness on functioning. The ratings of the CGI-S are as follows: 1 = normal, 2 = borderline ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, and 7 = among the most extremely ill. 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.	Baseline, Endpoint (last post-baseline visit up to Day 378)
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part I Score at Month 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 0-16 and higher scores are associated with more disability.	Baseline, Endpoint (last post-baseline visit up to Day 378)
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Score at Endpoint	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.	Baseline, Endpoint (last post-baseline visit up to Day 378)
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score at Endpoint	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.	Baseline, Endpoint (last post-baseline visit up to Day 378)
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Total Score at Endpoint	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 0-176, with 176 representing the worst (total) disability, and 0 representing no disability.	Baseline, Endpoint (last post-baseline visit up to Day 378)
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part IV Score at Endpoint	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 0-23 and higher scores are associated with more disability.	Baseline, Endpoint (last post-baseline visit up to Day 378)
Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Summary Index at Endpoint	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.	Baseline, Endpoint (last post-baseline visit up to Day 378)
Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Mobility Domain Score at Endpoint	The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Mobility (e.g., fear of falling when walking) includes 10 questions, each answered on a 5-point scale. 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.	Baseline, Endpoint (last post-baseline visit up to Day 378)
Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Activities of Daily Living Domain Score at Endpoint	The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Activities of Daily Living (e.g., difficulty cutting food) includes 6 questions, each answered on a 5-point scale. 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.	Baseline, Endpoint (last post-baseline visit up to Day 378)
Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Emotional Well-Being Domain Score at Endpoint	The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Emotional Well-being (e.g., feelings of isolation) includes 6 questions, each answered on a 5-point scale. 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.	Baseline, Endpoint (last post-baseline visit up to Day 378)
Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Stigma Domain Score at Endpoint	The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Stigma (e.g., social embarrassment) consists of 4 questions, each answered on a 5-point scale. 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.	Baseline, Endpoint (last post-baseline visit up to Day 378)
Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Social Support Domain Score at Endpoint	The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Social Support includes 3 questions, each answered on a 5-point scale. 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.	Baseline, Endpoint (last post-baseline visit up to Day 378)
Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Cognition Domain Score at Endpoint	The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Cognition includes 4 questions, each answered on a 5-point scale. 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.	Baseline, Endpoint (last post-baseline visit up to Day 378)
Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Communication Domain Score at Endpoint	The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Communication includes 3 questions, each answered on a 5-point scale. 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.	Baseline, Endpoint (last post-baseline visit up to Day 378)
Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Bodily Discomfort Domain Score at Endpoint	The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Bodily Discomfort includes 3 questions, each answered on a 5-point scale. 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.	Baseline, Endpoint (last post-baseline visit up to Day 378)
Change From Baseline in EuroQol Quality of Life Scale (EQ-5D) Summary Index at Endpoint	The EQ-5D is a participant answered questionnaire scoring 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. EQ-5D health states, defined by the EQ-5D descriptive system, are converted into a single summary index by applying a formula that essentially attaches values (also called QOL weights or QOL utilities) to each of the levels in each dimension. EQ-5D Summary Index values range from -0.11 to 1.00 with positive change indicating improvement.	Baseline, Endpoint (last post-baseline visit up to Day 378)
Change From Baseline in EuroQol Quality of Life Scale (EQ-5D) Visual Analogue Scale (VAS) at Endpoint	The EQ-5D VAS records the participant's self-rated health on a scale from 0-100 where 100 is the 'best imaginable health state' and 0 is the 'worst imaginable health state'.	Baseline, Endpoint (last post-baseline visit up to Day 378)
Change From Baseline in Zarit Burden Interview (ZBI) Total Score at Endpoint	The ZBI is a 22-item questionnaire regarding the caregiver/subject relationship and evaluates the caregiver's health condition, psychological well-being, finances and social life. Each question is answered on a 5-point scale (0=never, 1=rarely, 2=sometimes, 3=quite frequently, and 4=nearly always). The caregiver burden is evaluated by the total score (Range 0 to 88) obtained from the sum of the answers to the 22 questions. Higher scores are associated with a higher level of burden for the caregiver.	Baseline, Endpoint (last post-baseline visit up to Day 378)

Collaborators and Investigators

• Sponsor: AbbVie (prior sponsor, Abbott)
• Collaborators: Quintiles, Inc.

Publications and helpful links

General Publications

• Lew MF, Slevin JT, Kruger R, Martinez Castrillo JC, Chatamra K, Dubow JS, Robieson WZ, Benesh JA, Fung VS. Initiation and dose optimization for levodopa-carbidopa intestinal gel: Insights from phase 3 clinical trials. Parkinsonism Relat Disord. 2015 Jul;21(7):742-8. doi: 10.1016/j.parkreldis.2015.04.022. Epub 2015 Apr 28.
• Chang FC, Kwan V, van der Poorten D, Mahant N, Wolfe N, Ha AD, Griffith JM, Tsui D, Kim SD, Fung VS. Intraduodenal levodopa-carbidopa intestinal gel infusion improves both motor performance and quality of life in advanced Parkinson's disease. J Clin Neurosci. 2016 Mar;25:41-5. doi: 10.1016/j.jocn.2015.05.059. Epub 2016 Jan 14.
• Fernandez HH, Standaert DG, Hauser RA, Lang AE, Fung VS, Klostermann F, Lew MF, Odin P, Steiger M, Yakupov EZ, Chouinard S, Suchowersky O, Dubow J, Hall CM, Chatamra K, Robieson WZ, Benesh JA, Espay AJ. Levodopa-carbidopa intestinal gel in advanced Parkinson's disease: final 12-month, open-label results. Mov Disord. 2015 Apr;30(4):500-9. doi: 10.1002/mds.26123. Epub 2014 Dec 24.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: June 8, 2006
• First Submitted That Met QC Criteria: June 8, 2006
• First Posted (Estimate): June 9, 2006

Study Record Updates

• Last Update Posted (Estimate): January 16, 2015
• Last Update Submitted That Met QC Criteria: January 12, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: Parkinson's Disease; efficacy; levodopa; dyskinesia; carbidopa; DUOPA; levodopa/carbidopa intestinal gel; severe motor fluctuations
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunologic Factors; Dopamine Agonists; Dopamine Agents; Adjuvants, Immunologic; Antiparkinson Agents; Anti-Dyskinesia Agents; Aromatic Amino Acid Decarboxylase Inhibitors; Levodopa; Carbidopa; Carbidopa, levodopa drug combination
• Other Study ID Numbers: S187.3.004; 2006-005186-18 (EudraCT Number)