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

Advanced Parkinson's Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00335153
• Other study ID #: S187.3.004
• Secondary ID: 2006-005186-18
• Status: Completed
• Phase: Phase 3
• First received: June 8, 2006
• Last updated: January 12, 2015
• Start date: January 2008
• Est. completion date: June 2012

Study information

• Verified date: January 2015
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Health authority: Russia: Ministry of Health of the Russian FederationUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited States: Food and Drug AdministrationGermany: Federal Institute for Drugs and Medical DevicesCzech Republic: State Institute for Drug ControlItaly: The Italian Medicines AgencyFinland: Finnish Medicines AgencyNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)New Zealand: MedsafePoland: The Central Register of Clinical TrialsPortugal: National Pharmacy and Medicines InstituteAustralia: Department of Health and Ageing Therapeutic Goods AdministrationSpain: Agencia Española de Medicamentos y Productos SanitariosCanada: Health CanadaIsrael: Ministry of HealthThailand: Ministry of Public Health
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 354
• Est. completion date: June 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Parkinson's Disease
• Parkinson Disease

Intervention

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).

Device:
• CADD-Legacy® 1400 ambulatory infusion pump

• PEG tube
percutaneous endoscopic gastrostomy tube
• J-tube
jejunal tube

Locations

Country	Name	City	State
Australia	Site Reference ID/Investigator# 46429	Adelaide
Australia	Site Reference ID/Investigator# 46427	Heidelberg
Australia	Site Reference ID/Investigator# 46425	Westmead
Canada	Site Reference ID/Investigator# 54545	Edmonton
Canada	Site Reference ID/Investigator# 46433	Montreal
Canada	Site Reference ID/Investigator# 46434	Toronto
Czech Republic	Site Reference ID/Investigator# 46436	Brno
Czech Republic	Site Reference ID/Investigator# 46438	Hradec Kralove
Czech Republic	Site Reference ID/Investigator# 46435	Pardubice
Czech Republic	Site Reference ID/Investigator# 46437	Prague 2
Czech Republic	Site Reference ID/Investigator# 46439	Prague 5
Finland	Site Reference ID/Investigator# 48003	Lahti
Germany	Site Reference ID/Investigator# 48028	Berlin
Germany	Site Reference ID/Investigator# 48029	Berlin
Germany	Site Reference ID/Investigator# 48036	Freiburg
Germany	Site Reference ID/Investigator# 48034	Goettingen
Germany	Site Reference ID/Investigator# 48022	Hanau
Germany	Site Reference ID/Investigator# 48024	Hanover
Germany	Site Reference ID/Investigator# 48035	Mainz
Israel	Site Reference ID/Investigator# 49882	Tel Aviv
Italy	Site Reference ID/Investigator# 50131	Arcugnano
Italy	Site Reference ID/Investigator# 50132	Catania
Italy	Site Reference ID/Investigator# 50128	Genoa
Italy	Site Reference ID/Investigator# 50129	Lido di Camaiore
Italy	Site Reference ID/Investigator# 50130	Naples
Italy	Site Reference ID/Investigator# 50127	Rome
Netherlands	Site Reference ID/Investigator# 50138	Nijmegen
New Zealand	Site Reference ID/Investigator# 50126	Auckland
New Zealand	Site Reference ID/Investigator# 50123	Christchurch
New Zealand	Site Reference ID/Investigator# 50124	Hamilton
New Zealand	Site Reference ID/Investigator# 50125	Wellington
Poland	Site Reference ID/Investigator# 50140	Lodz
Poland	Site Reference ID/Investigator# 50139	Poznan
Portugal	Site Reference ID/Investigator# 50136	Almada
Portugal	Site Reference ID/Investigator# 50134	Coimbra
Portugal	Site Reference ID/Investigator# 50135	Lisbon
Portugal	Site Reference ID/Investigator# 50137	Porto
Russian Federation	Site Reference ID/Investigator# 50143	Kazan
Russian Federation	Site Reference ID/Investigator# 50141	Moscow
Russian Federation	Site Reference ID/Investigator# 50142	St. Petersburg
Russian Federation	Site Reference ID/Investigator# 50145	St. Petersburg
Russian Federation	Site Reference ID/Investigator# 50146	St. Petersburg
Russian Federation	Site Reference ID/Investigator# 50147	St. Petersburg
Spain	Site Reference ID/Investigator# 50152	Barcelona
Spain	Site Reference ID/Investigator# 50154	Barcelona
Spain	Site Reference ID/Investigator# 50155	Barcelona
Spain	Site Reference ID/Investigator# 50202	Barcelona
Spain	Site Reference ID/Investigator# 50153	Madrid
Thailand	Site Reference ID/Investigator# 50150	Bangkok
Thailand	Site Reference ID/Investigator# 50151	Bangkok
United Kingdom	Site Reference ID/Investigator# 50149	Liverpool
United Kingdom	Site Reference ID/Investigator# 50148	London
United States	Site Reference ID/Investigator# 50062	Augusta	Georgia
United States	Site Reference ID/Investigator# 50074	Baltimore	Maryland
United States	Site Reference ID/Investigator# 50080	Baltimore	Maryland
United States	Site Reference ID/Investigator# 50065	Birmingham	Alabama
United States	Site Reference ID/Investigator# 50077	Bradenton	Florida
United States	Site Reference ID/Investigator# 50058	Burlington	Vermont
United States	Site Reference ID/Investigator# 50050	Chicago	Illinois
United States	Site Reference ID/Investigator# 50078	Chicago	Illinois
United States	Site Reference ID/Investigator# 50043	Cincinnati	Ohio
United States	Site Reference ID/Investigator# 50044	Cleveland	Ohio
United States	Site Reference ID/Investigator# 50061	Englewood	Colorado
United States	Site Reference ID/Investigator# 50060	Fort Lauderdale	Florida
United States	Site Reference ID/Investigator# 50059	Fountain Valley	California
United States	Site Reference ID/Investigator# 50049	Gainesville	Florida
United States	Site Reference ID/Investigator# 50047	Jacksonville	Florida
United States	Site Reference ID/Investigator# 50045	Kirkland	Washington
United States	Site Reference ID/Investigator# 50064	Lexington	Kentucky
United States	Site Reference ID/Investigator# 50048	Los Angeles	California
United States	Site Reference ID/Investigator# 50072	Manhasset	New York
United States	Site Reference ID/Investigator# 50070	Milwaukee	Wisconsin
United States	Site Reference ID/Investigator# 50066	New York	New York
United States	Site Reference ID/Investigator# 50067	New York	New York
United States	Site Reference ID/Investigator# 50076	Oceanside	California
United States	Site Reference ID/Investigator# 50042	Omaha	Nebraska
United States	Site Reference ID/Investigator# 50068	Port Charlotte	Florida
United States	Site Reference ID/Investigator# 50069	Raleigh	North Carolina
United States	Site Reference ID/Investigator# 50075	Shreveport	Louisiana
United States	Site Reference ID/Investigator# 50073	St. Louis	Missouri
United States	Site Reference ID/Investigator# 50046	Tampa	Florida
United States	Site Reference ID/Investigator# 50079	Washington	District of Columbia
United States	Site Reference ID/Investigator# 50063	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
AbbVie (prior sponsor, Abbott)	Quintiles, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Czech Republic,  Finland,  Germany,  Israel,  Italy,  Netherlands,  New Zealand,  Poland,  Portugal,  Russian Federation,  Spain,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	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)	Yes
Primary	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)	Yes
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Primary	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)	Yes
Primary	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)	Yes
Primary	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)	Yes
Primary	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	Yes
Primary	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	Yes
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No

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