Patient- and Caregiver-reported Symptoms and Outcomes With Levodopa/Carbidopa Intestinal Gel for the Treatment of Advanced Parkinson's Disease

Parkinson's Disease Clinical Trial

— ADEQUA  

Official title:

Study on Patient- and Caregiver-reported Symptoms and Outcomes With Levodopa/Carbidopa Intestinal Gel for the Treatment of Advanced Parkinson's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02289729
• Other study ID #: P14-335
• Status: Completed
• Start date: October 2014
• Est. completion date: November 2016

Study information

• Verified date: November 2017
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Patient reported outcomes (PRO) have become an important endpoint assessed in clinical trials. It is important to understand the relationship between medication and patients' symptomatology, quality of life and well-being. We predict levodopa/carbidopa intestinal gel (LCIG; Duodopa) will significantly improve quality of life and emotional well-being compared to baseline in patients with advance Parkinson disease (APD) not well controlled with conventional treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: November 2016
• Est. primary completion date: November 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

• Patients with advanced levodopa-responsive Parkinson's disease, with at least, 2 hours "off" time or 2 hours of dyskinesia based on clinician's/investigator's medical judgment

• Patients with advanced Parkinson's disease with severe motor fluctuations and dyskinesia when combination of conventional PD treatments was unable to satisfactory control symptoms.

• Patients with advanced Parkinson's disease who meet the criteria for use of Levodopa/Carbidopa Intestinal Gel (LCIG) established in the summary of product characteristics, Spanish Neurology Society (SEN) guidelines, local/regional directories (CCAA) or site's protocols for use of LCIG in common clinical practice.

• The decision to treat with LCIG is made by the physician prior to any decision to approach the patient to participate in this study.

• Patients with a cognitive level enough to complete the questionnaires, confirmed by a Mini-mental state examination (MMSE) score of at least 26 points, according to the recommendation of the Movement Disorder Society (MDS) task force on dementia in Parkinson's Disease (PD)

Exclusion Criteria:

• LCIG's contraindications included in the Summary of Product Characteristics (product label)

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Parkinson's Disease Questionnaire-39 Item (PDQ-39) Global Score at Month 6	The PDQ-39 contains 39 items: mobility (items 1-10), activities of daily living (items 11-16), emotional well-being (items 17-22), stigma (items 23-26), social support (items 27-29), cognitions (items 30-33), communication (items 34-36), and bodily discomfort (items 37-39). Participants are asked to indicate the frequency of each event by selecting one of 5 options (score 0 to 4 on a Likert scale). The global score was calculated by expressing summed item scores as a percentage score ranging between 0 and 100. The lower scores indicate a better perceived health status and higher scores are associated with more health problems.	Baseline, Month 6 (±15 days)
Primary	Change From Baseline in PDQ-39 Mobility Domain Score at Month 6	The PDQ-39 contains 39 items grouped in 8 domains: mobility (items 1-10), activities of daily living (items 11-16), emotional well-being (items 17-22), stigma (items 23-26), social support (items 27-29), cognitions (items 30-33), communication (items 34-36), and bodily discomfort (items 37-39). Participants are asked to indicate the frequency of each event by selecting one of 5 options (Likert scale): never, occasionally, sometimes, often, always or cannot do at all, scoring 0, 1, 2, 3 or 4, respectively. The mobility domain score was calculated by expressing summed item scores as a percentage score ranging between 0 and 100. The lower scores indicate a better perceived health status and higher scores are associated with more health problems.	Baseline, Month 6 (±15 days)
Primary	Change From Baseline in PDQ-39 Activities of Daily Living Domain Score at Month 6	The PDQ-39 contains 39 items grouped in 8 domains: mobility (items 1-10), activities of daily living (items 11-16), emotional well-being (items 17-22), stigma (items 23-26), social support (items 27-29), cognitions (items 30-33), communication (items 34-36), and bodily discomfort (items 37-39). Participants are asked to indicate the frequency of each event by selecting one of 5 options (Likert scale): never, occasionally, sometimes, often, always or cannot do at all, scoring 0, 1, 2, 3 or 4, respectively. The activities of daily living domain score was calculated by expressing summed item scores as a percentage score ranging between 0 and 100. The lower scores indicate a better perceived health status and higher scores are associated with more health problems.	Baseline, Month 6 (±15 days)
Primary	Change From Baseline in PDQ-39 Emotional Well-Being Domain Score at Month 6	The PDQ-39 contains 39 items grouped in 8 domains: mobility (items 1-10), activities of daily living (items 11-16), emotional well-being (items 17-22), stigma (items 23-26), social support (items 27-29), cognitions (items 30-33), communication (items 34-36), and bodily discomfort (items 37-39). Participants are asked to indicate the frequency of each event by selecting one of 5 options (Likert scale): never, occasionally, sometimes, often, always or cannot do at all, scoring 0, 1, 2, 3 or 4, respectively. The emotional well-being domain score was calculated by expressing summed item scores as a percentage score ranging between 0 and 100. The lower scores indicate a better perceived health status and higher scores are associated with more health problems.	Baseline, Month 6 (±15 days)
Primary	Change From Baseline in PDQ-39 Stigma Domain Score at Month 6	The PDQ-39 contains 39 items grouped in 8 domains: mobility (items 1-10), activities of daily living (items 11-16), emotional well-being (items 17-22), stigma (items 23-26), social support (items 27-29), cognitions (items 30-33), communication (items 34-36), and bodily discomfort (items 37-39). Participants are asked to indicate the frequency of each event by selecting one of 5 options (Likert scale): never, occasionally, sometimes, often, always or cannot do at all, scoring 0, 1, 2, 3 or 4, respectively. The stigma domain score was calculated by expressing summed item scores as a percentage score ranging between 0 and 100. The lower scores indicate a better perceived health status and higher scores are associated with more health problems.	Baseline, Month 6 (±15 days)
Primary	Change From Baseline in PDQ-39 Social Support Domain Score at Month 6	The PDQ-39 contains 39 items grouped in 8 domains: mobility (items 1-10), activities of daily living (items 11-16), emotional well-being (items 17-22), stigma (items 23-26), social support (items 27-29), cognitions (items 30-33), communication (items 34-36), and bodily discomfort (items 37-39). Participants are asked to indicate the frequency of each event by selecting one of 5 options (Likert scale): never, occasionally, sometimes, often, always or cannot do at all, scoring 0, 1, 2, 3 or 4, respectively. The social support domain score was calculated by expressing summed item scores as a percentage score ranging between 0 and 100. The lower scores indicate a better perceived health status and higher scores are associated with more health problems.	Baseline, Month 6 (±15 days)
Primary	Change From Baseline in PDQ-39 Cognition Domain Score at Month 6	The PDQ-39 contains 39 items grouped in 8 domains: mobility (items 1-10), activities of daily living (items 11-16), emotional well-being (items 17-22), stigma (items 23-26), social support (items 27-29), cognitions (items 30-33), communication (items 34-36), and bodily discomfort (items 37-39). Participants are asked to indicate the frequency of each event by selecting one of 5 options (Likert scale): never, occasionally, sometimes, often, always or cannot do at all, scoring 0, 1, 2, 3 or 4, respectively. The cognition domain score was calculated by expressing summed item scores as a percentage score ranging between 0 and 100. The lower scores indicate a better perceived health status and higher scores are associated with more health problems.	Baseline, Month 6 (±15 days)
Primary	Change From Baseline in PDQ-39 Communication Domain Score at Month 6	The PDQ-39 contains 39 items grouped in 8 domains: mobility (items 1-10), activities of daily living (items 11-16), emotional well-being (items 17-22), stigma (items 23-26), social support (items 27-29), cognitions (items 30-33), communication (items 34-36), and bodily discomfort (items 37-39). Participants are asked to indicate the frequency of each event by selecting one of 5 options (Likert scale): never, occasionally, sometimes, often, always or cannot do at all, scoring 0, 1, 2, 3 or 4, respectively. The communication domain score was calculated by expressing summed item scores as a percentage score ranging between 0 and 100. The lower scores indicate a better perceived health status and higher scores are associated with more health problems.	Baseline, Month 6 (±15 days)
Primary	Change From Baseline in PDQ-39 Bodily Discomfort Domain Score at Month 6	The PDQ-39 contains 39 items grouped in 8 domains: mobility (items 1-10), activities of daily living (items 11-16), emotional well-being (items 17-22), stigma (items 23-26), social support (items 27-29), cognitions (items 30-33), communication (items 34-36), and bodily discomfort (items 37-39). Participants are asked to indicate the frequency of each event by selecting one of 5 options (Likert scale): never, occasionally, sometimes, often, always or cannot do at all, scoring 0, 1, 2, 3 or 4, respectively. The bodily discomfort domain score was calculated by expressing summed item scores as a percentage score ranging between 0 and 100. The lower scores indicate a better perceived health status and higher scores are associated with more health problems.	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in Unified Parkinson's Disease Rating Scale Part III (UPDRS-III): Motor Examination at Month 6	The UPDRS is an investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The UPDRS-III was used in ON state. The motor examination contains 27 items. Each item is scored in a Likert scale from 0 to 4. The UPDRS-III score was calculated summing the score of each item, ranging from 0 to 108, with higher score indicating more impairment.	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in the Non-Motor Symptom Scale (NMSS) Global Score at Month 6	The NMSS measures the frequency and severity of a range of non-motor symptoms in Parkinson's Disease. It consists of 30 questions grouped into 9 domains: cardiovascular including falls (items 1-2), sleep/fatigue (items 3-6), mood/cognition (items 7-12), perceptual problems/hallucinations (items 13-15), attention/memory (items 16-18), gastrointestinal tract (items 19-21), urinary (items 22-24), sexual function (items 25-26), and miscellaneous (pain, taste/smell, weight change, excessive sweating; items 27-30). Severity is rated on a scale from 0 (none) to 3 (severe) and frequency is rated on a scale from 1 (rarely) to 4 (very frequent). The global score was calculated summing the score of each item (severity x frequency), ranging from 0 to 360, with a lower score indicating fewer symptoms. A negative change from baseline indicates improvement in symptoms.	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in NMSS Cardiovascular Domain Score at Month 6	The NMSS measures the frequency and severity of a range of non-motor symptoms in Parkinson's Disease. It consists of 30 questions grouped into 9 domains: cardiovascular including falls (items 1-2), sleep/fatigue (items 3-6), mood/cognition (items 7-12), perceptual problems/hallucinations (items 13-15), attention/memory (items 16-18), gastrointestinal tract (items 19-21), urinary (items 22-24), sexual function (items 25-26), and miscellaneous (pain, taste/smell, weight change, excessive sweating; items 27-30). Severity is rated on a scale from 0 (none) to 3 (severe) and frequency is rated on a scale from 1 (rarely) to 4 (very frequent). The cardiovascular domain score ranges from 0 to 24 with a lower score indicating fewer symptoms. A negative change from baseline indicates improvement in symptoms.	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in NMSS Sleep/Fatigue Domain Score at Month 6	The NMSS measures the frequency and severity of a range of non-motor symptoms in Parkinson's Disease. It consists of 30 questions grouped into 9 domains: cardiovascular including falls (items 1-2), sleep/fatigue (items 3-6), mood/cognition (items 7-12), perceptual problems/hallucinations (items 13-15), attention/memory (items 16-18), gastrointestinal tract (items 19-21), urinary (items 22-24), sexual function (items 25-26), and miscellaneous (pain, taste/smell, weight change, excessive sweating; items 27-30). Severity is rated on a scale from 0 (none) to 3 (severe) and frequency is rated on a scale from 1 (rarely) to 4 (very frequent). The sleep/fatigue domain score ranges from 0 to 48 with a lower score indicating fewer symptoms. A negative change from baseline indicates improvement in symptoms.	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in NMSS Mood/Cognition Domain Score at Month 6	The NMSS measures the frequency and severity of a range of non-motor symptoms in Parkinson's Disease. It consists of 30 questions grouped into 9 domains: cardiovascular including falls (items 1-2), sleep/fatigue (items 3-6), mood/cognition (items 7-12), perceptual problems/hallucinations (items 13-15), attention/memory (items 16-18), gastrointestinal tract (items 19-21), urinary (items 22-24), sexual function (items 25-26), and miscellaneous (pain, taste/smell, weight change, excessive sweating; items 27-30). Severity is rated on a scale from 0 (none) to 3 (severe) and frequency is rated on a scale from 1 (rarely) to 4 (very frequent). The mood/cognition domain score ranges from 0 to 72 with a lower score indicating fewer symptoms. A negative change from baseline indicates improvement in symptoms.	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in NMSS Perceptual Problems/Hallucinations Domain Score at Month 6	The NMSS measures the frequency and severity of a range of non-motor symptoms in Parkinson's Disease. It consists of 30 questions grouped into 9 domains: cardiovascular including falls (items 1-2), sleep/fatigue (items 3-6), mood/cognition (items 7-12), perceptual problems/hallucinations (items 13-15), attention/memory (items 16-18), gastrointestinal tract (items 19-21), urinary (items 22-24), sexual function (items 25-26), and miscellaneous (pain, taste/smell, weight change, excessive sweating; items 27-30). Severity is rated on a scale from 0 (none) to 3 (severe) and frequency is rated on a scale from 1 (rarely) to 4 (very frequent). The perceptual problems/hallucinations domain score ranges from 0 to 36 with a lower score indicating fewer symptoms. A negative change from baseline indicates improvement in symptoms.	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in NMSS Attention/Memory Domain Score at Month 6	The NMSS measures the frequency and severity of a range of non-motor symptoms in Parkinson's Disease. It consists of 30 questions grouped into 9 domains: cardiovascular including falls (items 1-2), sleep/fatigue (items 3-6), mood/cognition (items 7-12), perceptual problems/hallucinations (items 13-15), attention/memory (items 16-18), gastrointestinal tract (items 19-21), urinary (items 22-24), sexual function (items 25-26), and miscellaneous (pain, taste/smell, weight change, excessive sweating; items 27-30). Severity is rated on a scale from 0 (none) to 3 (severe) and frequency is rated on a scale from 1 (rarely) to 4 (very frequent). The attention/memory domain score ranges from 0 to 36 with a lower score indicating fewer symptoms. A negative change from baseline indicates improvement in symptoms.	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in NMSS Gastrointestinal Tract Domain Score at Month 6	The NMSS measures the frequency and severity of a range of non-motor symptoms in Parkinson's Disease. It consists of 30 questions grouped into 9 domains: cardiovascular including falls (items 1-2), sleep/fatigue (items 3-6), mood/cognition (items 7-12), perceptual problems/hallucinations (items 13-15), attention/memory (items 16-18), gastrointestinal tract (items 19-21), urinary (items 22-24), sexual function (items 25-26), and miscellaneous (pain, taste/smell, weight change, excessive sweating; items 27-30). Severity is rated on a scale from 0 (none) to 3 (severe) and frequency is rated on a scale from 1 (rarely) to 4 (very frequent). The gastrointestinal tract domain score ranges from 0 to 36 with a lower score indicating fewer symptoms; a negative change from baseline indicates improvement in symptoms.	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in NMSS Urinary Domain Score at Month 6	The NMSS measures the frequency and severity of a range of non-motor symptoms in Parkinson's Disease. It consists of 30 questions grouped into 9 domains: cardiovascular including falls (items 1-2), sleep/fatigue (items 3-6), mood/cognition (items 7-12), perceptual problems/hallucinations (items 13-15), attention/memory (items 16-18), gastrointestinal tract (items 19-21), urinary (items 22-24), sexual function (items 25-26), and miscellaneous (pain, taste/smell, weight change, excessive sweating; items 27-30). Severity is rated on a scale from 0 (none) to 3 (severe) and frequency is rated on a scale from 1 (rarely) to 4 (very frequent). The urinary domain score ranges from 0 to 36 with a lower score indicating fewer symptoms.A negative change from baseline indicates improvement in symptoms.	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in NMSS Sexual Function Domain Score at Month 6	The NMSS measures the frequency and severity of a range of non-motor symptoms in Parkinson's Disease. It consists of 30 questions grouped into 9 domains: cardiovascular including falls (items 1-2), sleep/fatigue (items 3-6), mood/cognition (items 7-12), perceptual problems/hallucinations (items 13-15), attention/memory (items 16-18), gastrointestinal tract (items 19-21), urinary (items 22-24), sexual function (items 25-26), and miscellaneous (pain, taste/smell, weight change, excessive sweating; items 27-30). Severity is rated on a scale from 0 (none) to 3 (severe) and frequency is rated on a scale from 1 (rarely) to 4 (very frequent). The sexual function domain score ranges from 0 to 24 with a lower score indicating fewer symptoms. A negative change from baseline indicates improvement in symptoms.	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in NMSS Miscellaneous Domain Score at Month 6	The NMSS measures the frequency and severity of a range of non-motor symptoms in Parkinson's Disease. It consists of 30 questions grouped into 9 domains: cardiovascular including falls (items 1-2), sleep/fatigue (items 3-6), mood/cognition (items 7-12), perceptual problems/hallucinations (items 13-15), attention/memory (items 16-18), gastrointestinal tract (items 19-21), urinary (items 22-24), sexual function (items 25-26), and miscellaneous (pain, taste/smell, weight change, excessive sweating; items 27-30). Severity is rated on a scale from 0 (none) to 3 (severe) and frequency is rated on a scale from 1 (rarely) to 4 (very frequent). The miscellaneous domain score ranges from 0 to 48 with a lower score indicating fewer symptoms. A negative change from baseline indicates improvement in symptoms.	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in the Norris/Bond-Lader Visual Analogue Scale (VAS) Mean Global Score at Month 6	The Norris/Bond-Lader VAS measures emotional well-being status with a 16-item visual analogue mood rating scale. The VAS consisted of 16 visual analogue items each representing opposite extremes of mood, with the following labels at each end: alert/drowsy, calm/excited, strong/weak, muzzy/clear-headed, well-coordinated/clumsy, lethargic/energetic, contented/dreamy, incompetent/proficient, happy/sad, antagonistic/amicable, interested/bored, withdrawn/gregarious. These scales loaded on 3 domains (alert, strong, clear-headed, well-coordinated, energetic, quick-witted, attentive, proficient, interested); (contented, tranquil, happy, amicable, gregarious); (calm, relaxed). For each individual scale, a line was drawn between each mood state and its opposite and participants rated their current mood by placing a vertical mark on the line. Scores (global, and for each domain) ranged from 0 to 100, with lower scores indicating more positive mood.	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in the Norris/Bond-Lader Visual Analogue Scale (VAS) Alertness/Sedation Sub-Scale Score at Month 6	The Norris/Bond-Lader VAS measures emotional well-being status with a 16-item visual analogue mood rating scale. The VAS consisted of 16 visual analogue items each representing opposite extremes of mood, with the following labels at each end: alert/drowsy, calm/excited, strong/weak, muzzy/clear-headed, well-coordinated/clumsy, lethargic/energetic, contented/dreamy, incompetent/proficient, happy/sad, antagonistic/amicable, interested/bored, withdrawn/gregarious. These scales loaded on 3 domains (alert, strong, clear-headed, well-coordinated, energetic, quick-witted, attentive, proficient, interested); (contented, tranquil, happy, amicable, gregarious); (calm, relaxed). For each individual scale, a line was drawn between each mood state and its opposite and participants rated their current mood by placing a vertical mark on the line. Scores (global, and for each domain) ranged from 0 to 100, with lower scores indicating more positive mood.	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in the Norris/Bond-Lader Visual Analogue Scale (VAS) Contented/Discontented Sub-Scale Score at Month 6	The Norris/Bond-Lader VAS measures emotional well-being status with a 16-item visual analogue mood rating scale. The VAS consisted of 16 visual analogue items each representing opposite extremes of mood, with the following labels at each end: alert/drowsy, calm/excited, strong/weak, muzzy/clear-headed, well-coordinated/clumsy, lethargic/energetic, contented/dreamy, incompetent/proficient, happy/sad, antagonistic/amicable, interested/bored, withdrawn/gregarious. These scales loaded on 3 domains (alert, strong, clear-headed, well-coordinated, energetic, quick-witted, attentive, proficient, interested); (contented, tranquil, happy, amicable, gregarious); (calm, relaxed). For each individual scale, a line was drawn between each mood state and its opposite and participants rated their current mood by placing a vertical mark on the line. Scores (global, and for each domain) ranged from 0 to 100, with lower scores indicating more positive mood.	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in the Norris/Bond-Lader Visual Analogue Scale (VAS) Calmness/Relaxation Sub-Scale Score at Month 6	The Norris/Bond-Lader VAS measures emotional well-being status with a 16-item visual analogue mood rating scale. The VAS consisted of 16 visual analogue items each representing opposite extremes of mood, with the following labels at each end: alert/drowsy, calm/excited, strong/weak, muzzy/clear-headed, well-coordinated/clumsy, lethargic/energetic, contented/dreamy, incompetent/proficient, happy/sad, antagonistic/amicable, interested/bored, withdrawn/gregarious. These scales loaded on 3 domains (alert, strong, clear-headed, well-coordinated, energetic, quick-witted, attentive, proficient, interested); (contented, tranquil, happy, amicable, gregarious); (calm, relaxed). For each individual scale, a line was drawn between each mood state and its opposite and participants rated their current mood by placing a vertical mark on the line. Scores (global, and for each domain) ranged from 0 to 100, with lower scores indicating more positive mood.	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in Parkinson Fatigue Scale (PFS-16) at Month 6	The PFS-16 comprises 16 items with five polytomous response categories (strongly disagree, disagree, do not agree or disagree, agree, and strongly agree). Responses were scored from 0 (strongly disagree) to 4 (strongly agree), yielding a summed total score ranging from 0 (no fatigue) to 64 (most severe fatigue). The cut-point of = 3.30 was used to identified those perceiving fatigue to be a problem.	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in the Score of the Apathy Scale (AS) to Month 6	The AS is an inventory of 14 questions that assess cognitive and behavioral symptoms of emotional apathy. Each is rated from 0 to 3 on a Likert scale. The total scores for AS ranges from 0 (no apathy) to 42 (most apathetic). AS scores = 14 were considered apathetic.	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in Beck Depression Inventory, Second Edition (BDI-II) at Month 6	The BDI-II is a 21-item self-report multiple-choice inventory. Items are rated on a 4-point scale ranging from 0 to 3 based on severity of each item. The maximum total score is 63. Raw scores from 0-13 indicates minimal depression, 14-19 indicates mild depression, 20-28 indicates moderate depression, and 29-63 indicates severe depression.	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in Beck Anxiety Inventory (BAI) at Month 6	The BAI is a 21-item self-report multiple-choice inventory. Items are rated on a 4-point scale ranging from 0 to 3 based on severity of each item. The maximum total score is 63. Raw scores from 0-7 indicates minimal anxiety, 8-15 indicates mild anxiety, 16-25 indicates moderate anxiety, and 25-63 indicates severe anxiety.	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in the Treatment Satisfaction With Medicines Questionnaire (SATMED-Q) Composite Score at Month 6	The SATMED-Q is a 17-item questionnaire. Items are grouped in 6 domains: undesirable side effects (items 1-3), treatment effectiveness (items 4-6), convenience of use (items 7-9), impact on daily living activities (items 10-12), medical care (items 13-14), and global satisfaction (items 15-17). Items are rated on a 5-point scale ranging from 0 to 4. Summing up the direct scores of the items yields a total composite score ranging between 0 and 68, which was transformed to a minimum of 0 (most satisfied) and a maximum of 100 (least satisfied).	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in the Treatment Satisfaction With Medicines Questionnaire (SATMED-Q) Undesirable Side Effects at Month 6	The SATMED-Q is a 17-item questionnaire. Items are grouped in 6 domains: undesirable side effects (items 1-3), treatment effectiveness (items 4-6), convenience of use (items 7-9), impact on daily living activities (items 10-12), medical care (items 13-14), and global satisfaction (items 15-17). Items are rated on a 4-point scale ranging from 0 to 4. Summing up the direct scores of the items yields a total undesirable side effects score ranging between 0 and 12, which was transformed to a minimum of 0 (most satisfied) and a maximum of 100 (least satisfied).	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in the Treatment Satisfaction With Medicines Questionnaire (SATMED-Q) Treatment Effectiveness at Month 6	The SATMED-Q is a 17-item questionnaire. Items are grouped in 6 domains: undesirable side effects (items 1-3), treatment effectiveness (items 4-6), convenience of use (items 7-9), impact on daily living activities (items 10-12), medical care (items 13-14), and global satisfaction (items 15-17). Items are rated on a 4-point scale ranging from 0 to 4. Summing up the direct scores of the items yields a total treatment effectiveness score ranging between 0 and 12, which was transformed to a minimum of 0 (most satisfied) and a maximum of 100 (least satisfied).	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in the Treatment Satisfaction With Medicines Questionnaire (SATMED-Q) Convenience of Use at Month 6	The SATMED-Q is a 17-item questionnaire. Items are grouped in 6 domains: undesirable side effects (items 1-3), treatment effectiveness (items 4-6), convenience of use (items 7-9), impact on daily living activities (items 10-12), medical care (items 13-14), and global satisfaction (items 15-17). Items are rated on a 4-point scale ranging from 0 to 4. Summing up the direct scores of the items yields a total convenience of use score ranging between 0 and 12, which was transformed to a minimum of 0 (most satisfied) and a maximum of 100 (least satisfied).	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in the Treatment Satisfaction With Medicines Questionnaire (SATMED-Q) Impact on Daily Living Activities at Month 6	The SATMED-Q is a 17-item questionnaire. Items are grouped in 6 domains: undesirable side effects (items 1-3), treatment effectiveness (items 4-6), convenience of use (items 7-9), impact on daily living activities (items 10-12), medical care (items 13-14), and global satisfaction (items 15-17). Items are rated on a 4-point scale ranging from 0 to 4. Summing up the direct scores of the items yields a total impact on daily living activities score ranging between 0 and 12, which was transformed to a minimum of 0 (most satisfied) and a maximum of 100 (least satisfied).	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in the Treatment Satisfaction With Medicines Questionnaire (SATMED-Q) Medical Care at Month 6	The SATMED-Q is a 17-item questionnaire. Items are grouped in 6 domains: undesirable side effects (items 1-3), treatment effectiveness (items 4-6), convenience of use (items 7-9), impact on daily living activities (items 10-12), medical care (items 13-14), and global satisfaction (items 15-17). Items are rated on a 4-point scale ranging from 0 to 4. Summing up the direct scores of the items yields a total medical care score ranging between 0 and 8, which was transformed to a minimum of 0 (most satisfied) and a maximum of 100 (least satisfied).	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in the Treatment Satisfaction With Medicines Questionnaire (SATMED-Q) Global Satisfaction at Month 6	The SATMED-Q is a 17-item questionnaire. Items are grouped in 6 domains: undesirable side effects (items 1-3), treatment effectiveness (items 4-6), convenience of use (items 7-9), impact on daily living activities (items 10-12), medical care (items 13-14), and global satisfaction (items 15-17). Items are rated on a 4-point scale ranging from 0 to 4. Summing up the direct scores of the items yields a total global satisfaction score ranging between 0 and 12, which was transformed to a minimum of 0 (most satisfied) and a maximum of 100 (least satisfied).	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in the Scale of Quality of Life of Caregivers (SQLC) Composite Score at Month 6	The SQLC is designed to both qualitatively and quantitatively evaluate the impact of a patient's disease on the caregiver's quality of life. The SQLC questionnaire consists of 16 questions that evaluate 3 domains: professional activities (questions 1-4), social and leisure activities (questions 5-9), and caregiving responsibilities (questions 10-16). Composite scores range from 0 to 149, with higher scores indicating higher quality of life.	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in the Scale of Quality of Life of Caregivers (SQLC) Professional Activities at Month 6	The SQLC is designed to both qualitatively and quantitatively evaluate the impact of a patient's disease on the caregiver's quality of life. The SQLC questionnaire consists of 16 questions that evaluate 3 domains: professional activities (questions 1-4), social and leisure activities (questions 5-9), and caregiving responsibilities (questions 10-16). Professional activities scores range from 0 to 38, with higher scores indicating higher quality of life.	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in the Scale of Quality of Life of Caregivers (SQLC) Social and Leisure Activities at Month 6	The SQLC is designed to both qualitatively and quantitatively evaluate the impact of a patient's disease on the caregiver's quality of life. The SQLC questionnaire consists of 16 questions that evaluate 3 domains: professional activities (questions 1-4), social and leisure activities (questions 5-9), and caregiving responsibilities (questions 10-16). Social and leisure activities scores range from 0 to 58, with higher scores indicating higher quality of life.	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in the Scale of Quality of Life of Caregivers (SQLC) Caregiving Responsibilities at Month 6	The SQLC is designed to both qualitatively and quantitatively evaluate the impact of a patient's disease on the caregiver's quality of life. The SQLC questionnaire consists of 16 questions that evaluate 3 domains: professional activities (questions 1-4), social and leisure activities (questions 5-9), and caregiving responsibilities (questions 10-16). Caregiving responsibilities scores range from 0 to 53, with higher scores indicating higher quality of life.	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in Zarit Burden Interview (ZBI) at Month 6	The ZBI is a 22-item questionnaire in which caregivers must evaluate the level of agreement on a 5-point Likert scale from 0 to 4. The total score is obtained by the sum of the scores of the items. This total score represents a level of caregiver burden, with a range of 0 indicating no burden to 88 indicating completely overloaded.	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in the Caregiver Stress Index (CSI) at Month 6	The CSI is a 13-item questionnaire based on identified common stressors. Answers are in yes/no format. Scoring is 1 point for each "yes" and 0 for each "no". The total score is obtained by the sum of the scores of the items. Minimum score is 0 (no stress) and maximum score is 13 (most stress). A score = 7 indicates a high level of stress.	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in Goldberg Anxiety and Depression Score (GADS): Depression Sub-Scale for Caregivers at Month 6	The GADS is an 18-item self-report symptom inventory made up of two sub-scales, one for the detection of anxiety and another one for the detection of depression. Both sub-scales are composed of 9 questions. Answers are in yes/no format. Scoring is 1 point for each "yes" and 0 for each "no", with a total sub-scale score of 0 (no anxiety/depression) to 9 (worst anxiety/depression). In the Spanish validation of GADS, the cutoff point to consider probable anxiety disorder is 4 and 2 for probable depression.	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in Goldberg Anxiety and Depression Score (GADS): Anxiety Sub-Scale for Caregivers at Month 6	The GADS is an 18-item self-report symptom inventory made up of two sub-scales, one for the detection of anxiety and another one for the detection of depression. Both sub-scales are composed of 9 questions. Answers are in yes/no format. Scoring is 1 point for each "yes" and 0 for each "no", with a total sub-scale score of 0 (no anxiety/depression) to 9 (worst anxiety/depression). In the Spanish validation of GADS, the cutoff point to consider probable anxiety disorder is 4 and 2 for probable depression.	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in Work Productivity and Activity Impairment (WPAI) Questionnaire: Mean Percentage of Work Time Missed (Absenteeism) at Month 6	Absenteeism, presented as the mean percentage of work time missed due to caregiving (as reported on the WPAI), and calculated as: 100*number of hours of work missed due to caregiving / (number of hours of work missed due to caregiving + number of hours worked). WPAI is a questionnaire used to evaluate lost productivity; scores are presented as percentages (multiplying the scores by 100), with 0% representing no impact on productivity and 100% representing complete impact on productivity.	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in WPAI Questionnaire: Mean Percentage of Impairment While Working Due to Caregiving (Presenteeism)	Presenteeism (the extent to which caregiving decreased productivity) is presented as the mean percentage of impairment while working due to caregiving, and calculated as: 100*scale value of question 5 on the WPAI (between 0 and 10) / 10. WPAI is a questionnaire used to evaluate lost productivity; scores are presented as percentages (multiplying the scores by 100), with 0% representing no impact on productivity and 100% representing complete impact on productivity.	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in WPAI Questionnaire: Mean Percentage of Overall Work Productivity Impairment (OWPI) Due to Caregiving	The mean percentage of OWPI due to caregiving (based on the WPAI questionnaire) is presented, calculated as: Absenteeism (%) + extent to which caregiving decreased productivity (%)* [number of hours worked / (number of hours of work missed due to caregiving + number of hours worked)]. WPAI is a questionnaire used to evaluate lost productivity; scores are presented as percentages (multiplying the scores by 100), with 0% representing no impact on productivity and 100% representing complete impact on productivity.	Baseline, Month 6 (±15 days)
Secondary	Change From Baseline in WPAI Questionnaire: Mean Percentage of Activity Impairment Due to Caregiving	Activity impairment due to caregiving (the extent to which caregiving affected the ability to perform usual daily activities) is presented as the mean percentage of activity impairment, calculated as 100*scale value of WPAI question 6 (between 0 and 10) / 10. WPAI is a questionnaire used to evaluate lost productivity; scores are presented as percentages (multiplying the scores by 100), with 0% representing no impact on productivity/activity and 100% representing complete impact on productivity/activity.	Baseline, Month 6 (±15 days)
Secondary	Correlation Between Participants' Quality of Life (PDQ-39) and Different Questionnaires at Baseline	Spearman correlation statistics were calculated for the quality of life of the participants (Global PDQ-39, see Outcome Measure 1) and the following scales: UPDRS-III (see Outcome Measure 10), UPDRS-IV (see description below), NMSS (see Outcome Measure 11), BAI (see Outcome Measure 28), BDI-III (see Outcome Measure 27), AS (see Outcome Measure 26), PFS (see Outcome Measure 25), Norris Bond-Lader (NBL) Alertness-Sedation (A-S; see Outcome Measure 22), NBL Contented-Discontented (C-D; see Outcome Measure 23), NBL Calm-Relaxed (C-R; see Outcome Measure 24), ZBI (see Outcome Measure 40), GADS-Anxiety (see Outcome Measure 43), and GADS-Depression (see Outcome Measure 42).; The UPDRS-IV contains 11 items, each scored in a Likert scale from 0 (normal) to 4 (severe); or a 2-point scale (yes/no format), with 1 point for "yes" and 0 for "no." The global score was calculated summing the score of each item, ranging from 0 to 23, where higher scores are associated with more disability.	Baseline
Secondary	Correlation Between Participants' Quality of Life (PDQ-39) and Different Questionnaires at Month 6	Spearman correlation statistics were calculated for the quality of life of the participants (Global PDQ-39, see Outcome Measure 1) and the following scales: UPDRS-III (see Outcome Measure 10), UPDRS-IV (see description below), NMSS (see Outcome Measure 11), BAI (see Outcome Measure 28), BDI-III (see Outcome Measure 27), AS (see Outcome Measure 26), PFS (see Outcome Measure 25), Norris Bond-Lader (NBL) Alertness-Sedation (A-S; see Outcome Measure 22), NBL Contented-Discontented (C-D; see Outcome Measure 23), NBL Calm-Relaxed (C-R; see Outcome Measure 24), ZBI (see Outcome Measure 40), GADS-Anxiety (see Outcome Measure 43), and GADS-Depression (see Outcome Measure 42).; The UPDRS-IV contains 11 items, each scored in a Likert scale from 0 (normal) to 4 (severe); or a 2-point scale (yes/no format), with 1 point for "yes" and 0 for "no." The global score was calculated summing the score of each item, ranging from 0 to 23, where higher scores are associated with more disability.	Month 6 (±15 days)
Secondary	Correlation Between Caregivers' Quality of Life (SQLC) and Different Questionnaires at Baseline	Spearman correlation statistics were calculated for the quality of life of the caregivers (Global SQLC, see Outcome Measure ) and the following scales: ZBI (see Outcome Measure 40), GADS-Anxiety (see Outcome Measure 43), and GADS-Depression (see Outcome Measure 42), NBL A-S (see Outcome Measure 22), NBL C-D (see Outcome Measure 23), NBL C-R (see Outcome Measure 24), Global PDQ-39 (see Outcome Measure 1), UPDRS-III (see Outcome Measure 10), UPDRS-IV (see description below), and Global NMSS (see Outcome Measure 11).; The UPDRS-IV contains 11 items, each scored in a Likert scale from 0 (normal) to 4 (severe); or a 2-point scale (yes/no format), with 1 point for "yes" and 0 for "no." The global score was calculated summing the score of each item, ranging from 0 to 23, where higher scores are associated with more disability.	Baseline
Secondary	Correlation Between Caregivers' Quality of Life (SQLC) and Different Questionnaires at Month 6	Spearman correlation statistics were calculated for the quality of life of the caregivers (Global SQLC, see Outcome Measure ) and the following scales: ZBI (see Outcome Measure 40), GADS-Anxiety (see Outcome Measure 43), and GADS-Depression (see Outcome Measure 42), NBL A-S (see Outcome Measure 22), NBL C-D (see Outcome Measure 23), NBL C-R (see Outcome Measure 24), Global PDQ-39 (see Outcome Measure 1), UPDRS-III (see Outcome Measure 10), UPDRS-IV (see description below), and Global NMSS (see Outcome Measure 11).; The UPDRS-IV contains 11 items, each scored in a Likert scale from 0 (normal) to 4 (severe); or a 2-point scale (yes/no format), with 1 point for "yes" and 0 for "no." The global score was calculated summing the score of each item, ranging from 0 to 23, where higher scores are associated with more disability.	Month 6 (±15 days)