Idiopathic Parkinson's Disease
Conditions
Keywords
Rotigotine, Neupro®, Non-motor symptoms
Brief summary
The primary objective of this study was to demonstrate that Rotigotine improves non-motor symptoms compared to Placebo in subjects with Parkinson's Disease.
Interventions
OTHERPlacebo
Placebo patches of 2, 4, 6 & 8 mg / 24 hours Daily application of Placebo patches starting at 2 mg / 24 hours (early Parkinson's Disease (PD) patients) or 4 mg / 24 hours (advanced PD patients). Dose was up-titrated in weekly increments of 2 mg / 24 hours until optimal or maximal dose was reached. Maximal dose was 8 mg / 24 hours for early PD patients and 16 mg / 24 hours for advanced PD patients. Optimal or maximal dose was maintained for 12 weeks followed by a de-escalation by 2 mg / 24 hours every other day.
DRUGRotigotine
Rotigotine patches of 2, 4, 6, and 8 mg / 24 hours Once daily application of Rotigotine patches starting at 2 mg / 24 hours (early Parkinson's Disease (PD) patients) or 4 mg / 24 hours (advanced PD patients). Dose was up-titrated in weekly increments of 2 mg / 24 hours until optimal or maximal dose was reached. Maximal dose is 8 mg / 24 hours for early PD patients and 16 mg / 24 hours for advanced PD patients. Optimal or maximal dose was maintained for 12 weeks followed by a de-escalation by 2 mg / 24 hours every other day.
Sponsors
UCB Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject is male or female, ≥18 years of age * Subject has idiopathic Parkinson's disease with at least 2 of the following cardinal signs being present: bradykinesia, resting tremor, rigidity or postural instability, and without any other known or suspected cause of Parkinsonism * Subject has a Hoehn and Yahr stage score ≤4 * Subject has a total Non-Motor Symptoms Scale (NMSS) score ≥40 * If the subject is taking levodopa (L-DOPA), he/she must be on a stable dose of L-DOPA (in combination with benserazide or carbidopa) for at least 28 days prior to the Baseline Visit * If the subject is receiving anticholinergics, monoamine oxidase (MAO) B inhibitors, or amantadine, he/she must have been on a stable dose for at least 28 days prior to the Baseline Visit and must be maintained on that dose for the duration of the study
Exclusion criteria
* Subject discontinued from previous therapy with a dopamine agonist after an adequate length of treatment, at an adequate dose, due to lack of efficacy as assessed by the investigator * Subject is receiving therapy with 1 of the following drugs, either concurrently or within 28 days prior to the Baseline Visit: alpha-methyl dopa, metoclopramide, reserpine, neuroleptics (except specific atypical neuroleptics: olanzapine, ziprasidone, aripiprazole, clozapine, and quetiapine), monoamine oxidase-A (MAO-A) inhibitors, methylphenidate, amphetamine, or other dopamine agonists (DAs) * Subject is receiving central nervous system (CNS) therapy (eg, sedatives, hypnotics, selective serotonin reuptake inhibitors \[SSRIs\], anxiolytics, or other sleep-modifying medication) unless dose has been stable daily for at least 28 days prior to the Baseline Visit and is likely to remain stable for the duration of the study * Subject has evidence of an impulse control disorder according to the modified Minnesota Impulsive Disorders Interview at the Screening Visit (Visit 1), confirmed by a positive structured clinical interview
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to the End of Maintenance in Total Nonmotor Symptoms Scale (NMSS) Score | From Baseline (Day 1) to end of 12-week Maintenance (Day 84) | The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in the following 9 domain categories: cardiovascular, including falls; sleep/fatigue; mood/cognition; perceptual problems/hallucinations; attention/memory; gastrointestinal tract; urinary; sexual function; miscellaneous. Severity and frequency are rated using a 4-point scale ranging from 0 (none) to 3 (severe; major source of distress or disturbance to subject) for severity and from 1 (rarely) to 4 (very frequent \[daily or all the time\]) for frequency. The total NMSS score ranges from 0 to 350. A negative change from Baseline to end of Maintenance indicates an improvement in NMSS. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to the End of Maintenance in Health-related Quality of Life (HRQL) Measured by a 39-item Parkinson's Disease Questionnaire (PDQ-39) | From Baseline (Day 1) to end of 12-week Maintenance (Day 84) | Parkinson's Disease Questionnaire - 39 (PDQ-39) is a self-administered questionnaire. It comprises of 39 questions, relating to eight key areas of health and daily activities, including both Motor and Non-motor symptoms. It is scored on a scale of zero to 100, with lower scores indicating better health and high scores more severe symptoms in change from Baseline to end of Maintenance. |
| Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Cardiovascular | From Baseline (Day 1) to end of 12-week Maintenance (Day 84) | The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in 9 different domains. Severity (ranges: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) and frequency (ranges: 1 = Rarely (\<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) are rated using a 4-point scale. The final score is derived from multiplying the severity score and the frequency score. A negative change from Baseline to end of Maintenance indicates an improvement in NMSS. The possible min/max final scores per subdomain are calculated as follows: Range of final score per subdomain: 0 - 12 per question multiplied by the number of questions per subdomain: Subdomain Cardiovascular (2 questions): range 0 - 24 |
| Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Sleep/Fatigue | From Baseline (Day 1) to end of 12-week Maintenance (Day 84) | The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in 9 different domains. Severity (ranges: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) and frequency (ranges: 1 = Rarely (\<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) are rated using a 4-point scale. The final score is derived from multiplying the severity score and the frequency score. A negative change from Baseline to end of Maintenance indicates an improvement in NMSS. The possible min/max final scores per subdomain are calculated as follows: Range of final score per subdomain: 0 - 12 per question multiplied by the number of questions per subdomain: Subdomain Sleep/Fatigue (4 questions): range 0-48 |
| Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Mood/Cognition | From Baseline (Day 1) to end of 12-week Maintenance (Day 84) | The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in 9 different domains. Severity (ranges: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) and frequency (ranges: 1 = Rarely (\<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) are rated using a 4-point scale. The final score is derived from multiplying the severity score and the frequency score. A negative change from Baseline to end of Maintenance indicates an improvement in NMSS. The possible min/max final scores per subdomain are calculated as follows: Range of final score per subdomain: 0 - 12 per question multiplied by the number of questions per subdomain: Subdomain Mood/Cognition (6 questions): range 0 - 72 |
| Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Perception/Hallucinations | From Baseline (Day 1) to end of 12-week Maintenance (Day 84) | The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in 9 different domains. Severity (ranges: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) and frequency (ranges: 1 = Rarely (\<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) are rated using a 4-point scale. The final score is derived from multiplying the severity score and the frequency score. A negative change from Baseline to end of Maintenance indicates an improvement in NMSS. The possible min/max final scores per subdomain are calculated as follows: Range of final score per subdomain: 0 - 12 per question multiplied by the number of questions per subdomain: Subdomain Perception/Hallucinations (3 questions): range 0 - 36 |
| Change From Baseline to the End of Maintenance in Total Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score | From Baseline (Day 1) to end of 12-week Maintenance (Day 84) | The Unified Parkinson's Disease Rating Scale (UPDRS) Part III is a scale for the assessment of function in Parkinson's Disease. UPDRS Part III measures Motor Function. It consists of 14 items with 27 questions, each ranging from 0 to 4. The sum score for the UPDRS Part III ranges from 0 to 108. A higher score indicates greater disability. A negative change from Baseline to end of Maintenance score indicates improvement. |
| Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Gastrointestinal Tract | From Baseline (Day 1) to end of 12-week Maintenance (Day 84) | The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in 9 different domains. Severity (ranges: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) and frequency (ranges: 1 = Rarely (\<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) are rated using a 4-point scale. The final score is derived from multiplying the severity score and the frequency score. A negative change from Baseline to end of Maintenance indicates an improvement in NMSS. The possible min/max final scores per subdomain are calculated as follows: Range of final score per subdomain: 0 - 12 per question multiplied by the number of questions per subdomain: Subdomain Gastrointestinal tract (3 questions): range 0 - 36 |
| Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Urinary | From Baseline (Day 1) to end of 12-week Maintenance (Day 84) | The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in 9 different domains. Severity (ranges: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) and frequency (ranges: 1 = Rarely (\<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) are rated using a 4-point scale. The final score is derived from multiplying the severity score and the frequency score. A negative change from Baseline to end of Maintenance indicates an improvement in NMSS. The possible min/max final scores per subdomain are calculated as follows: Range of final score per subdomain: 0 - 12 per question multiplied by the number of questions per subdomain: Subdomain Urinary (3 questions): range 0 - 36 |
| Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Sexual Function | From Baseline (Day 1) to end of 12-week Maintenance (Day 84) | The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in 9 different domains. Severity (ranges: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) and frequency (ranges: 1 = Rarely (\<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) are rated using a 4-point scale. The final score is derived from multiplying the severity score and the frequency score. A negative change from Baseline to end of Maintenance indicates an improvement in NMSS. The possible min/max final scores per subdomain are calculated as follows: Range of final score per subdomain: 0 - 12 per question multiplied by the number of questions per subdomain: Subdomain Sexual function (2 questions): range 0 - 24 |
| Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Miscellaneous | From Baseline (Day 1) to end of 12-week Maintenance (Day 84) | The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in 9 different domains. Severity (ranges: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) and frequency (ranges: 1 = Rarely (\<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) are rated using a 4-point scale. The final score is derived from multiplying the severity score and the frequency score. A negative change from Baseline to end of Maintenance indicates an improvement in NMSS. The possible min/max final scores per subdomain are calculated as follows: Range of final score per subdomain: 0 - 12 per question multiplied by the number of questions per subdomain: Subdomain Miscellaneous (4 questions): range 0 - 48 |
| Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Attention/Memory, | From Baseline (Day 1) to end of 12-week Maintenance (Day 84) | The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in 9 different domains. Severity (ranges: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) and frequency (ranges: 1 = Rarely (\<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) are rated using a 4-point scale. The final score is derived from multiplying the severity score and the frequency score. A negative change from Baseline to end of Maintenance indicates an improvement in NMSS. The possible min/max final scores per subdomain are calculated as follows: Range of final score per subdomain: 0 - 12 per question multiplied by the number of questions per subdomain: Subdomain Attention/Memory (3 questions): range 0 - 36 |
Countries
Austria, Belgium, Bulgaria, Czechia, France, Germany, Hungary, Italy, Romania, Slovakia, Spain, Switzerland
Participant flow
Recruitment details
The study was conducted in 71 sites spread across 12 countries, with 349 subjects randomized. The study duration per subject was up to 29 weeks. The Participant Flow consists of patients in the Enrolled Set (ES). The Enrolled Set (ES) includes all subjects who signed the Informed Consent Form.
Pre-assignment details
Eligibility was assessed during the Screening Period, which lasted up to 4 weeks prior to the Baseline Visit. Eligible subjects returned for a Baseline Visit, during which all Baseline assessments were performed and then the subject was randomized to either Rotigotine or Placebo.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo : Placebo patches of 2, 4, 6 & 8 mg / 24 hours Daily application of Placebo patches starting at 2 mg / 24 hours (early Parkinson's Disease (PD) patients) or 4 mg / 24 hours (advanced PD patients). Dose will be up-titrated in weekly increments of 2 mg / 24 hours until optimal or maximal dose is reached. Maximal dose is 8 mg / 24 hours for early PD patients and 16 mg / 24 hours for advanced PD patients.
Optimal or maximal dose will be maintained for 12 weeks followed by a de-escalation by 2 mg / 24 hours every other day. | 125 |
| Rotigotine Rotigotine : Rotigotine patches of 2, 4, 6, and 8 mg / 24 hours
Once daily application of Rotigotine patches starting at 2 mg / 24 hours (early Parkinson's Disease (PD) patients) or 4 mg / 24 hours (advanced PD patients). Dose will be up-titrated in weekly increments of 2 mg / 24 hours until optimal or maximal dose is reached. Maximal dose is 8 mg / 24 hours for early PD patients and 16 mg / 24 hours for advanced PD patients.
Optimal or maximal dose will be maintained for 12 weeks followed by a de-escalation by 2 mg / 24 hours every other day. | 224 |
| Total | 349 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative reason | 0 | 1 |
| Overall Study | Adverse Event | 9 | 27 |
| Overall Study | Follow up call was not done | 1 | 0 |
| Overall Study | Lack of Efficacy | 2 | 1 |
| Overall Study | Patient was 1 month late for Visit 10 | 0 | 1 |
| Overall Study | Refusal to down titrate study drug | 0 | 1 |
| Overall Study | Safety follow up not done by mistake | 0 | 1 |
| Overall Study | Withdrawal by Subject | 10 | 12 |
Baseline characteristics
| Characteristic | Placebo | Rotigotine | Total |
|---|---|---|---|
| Age, Continuous | 66.6 years STANDARD_DEVIATION 9.8 | 68.0 years STANDARD_DEVIATION 9.4 | 67.5 years STANDARD_DEVIATION 9.6 |
| Age, Customized < 65 years | 51 participants | 74 participants | 125 participants |
| Age, Customized >= 65 years | 74 participants | 150 participants | 224 participants |
| Body Mass Index (BMI) | 27.593 kilogram per square meter STANDARD_DEVIATION 4.505 | 27.047 kilogram per square meter STANDARD_DEVIATION 4.348 | 27.243 kilogram per square meter STANDARD_DEVIATION 4.406 |
| Height | 167.42 centimeter STANDARD_DEVIATION 10.17 | 168.54 centimeter STANDARD_DEVIATION 8.56 | 168.14 centimeter STANDARD_DEVIATION 9.17 |
| Region of Enrollment Austria | 2 participants | 1 participants | 3 participants |
| Region of Enrollment Belgium | 4 participants | 9 participants | 13 participants |
| Region of Enrollment Bulgaria | 30 participants | 51 participants | 81 participants |
| Region of Enrollment Czech Republic | 8 participants | 13 participants | 21 participants |
| Region of Enrollment France | 3 participants | 6 participants | 9 participants |
| Region of Enrollment Germany | 15 participants | 24 participants | 39 participants |
| Region of Enrollment Hungary | 8 participants | 11 participants | 19 participants |
| Region of Enrollment Italy | 9 participants | 19 participants | 28 participants |
| Region of Enrollment Romania | 18 participants | 36 participants | 54 participants |
| Region of Enrollment Slovakia | 15 participants | 28 participants | 43 participants |
| Region of Enrollment Spain | 12 participants | 23 participants | 35 participants |
| Region of Enrollment Switzerland | 1 participants | 3 participants | 4 participants |
| Sex: Female, Male Female | 58 Participants | 95 Participants | 153 Participants |
| Sex: Female, Male Male | 67 Participants | 129 Participants | 196 Participants |
| Weight | 77.52 kilogram STANDARD_DEVIATION 14.9 | 76.97 kilogram STANDARD_DEVIATION 13.66 | 77.16 kilogram STANDARD_DEVIATION 14.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 21 / 125 | 66 / 223 |
| serious Total, serious adverse events | 4 / 125 | 8 / 223 |
Outcome results
Primary
Change From Baseline to the End of Maintenance in Total Nonmotor Symptoms Scale (NMSS) Score
The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in the following 9 domain categories: cardiovascular, including falls; sleep/fatigue; mood/cognition; perceptual problems/hallucinations; attention/memory; gastrointestinal tract; urinary; sexual function; miscellaneous. Severity and frequency are rated using a 4-point scale ranging from 0 (none) to 3 (severe; major source of distress or disturbance to subject) for severity and from 1 (rarely) to 4 (very frequent \[daily or all the time\]) for frequency. The total NMSS score ranges from 0 to 350. A negative change from Baseline to end of Maintenance indicates an improvement in NMSS.
Time frame: From Baseline (Day 1) to end of 12-week Maintenance (Day 84)
Population: This analysis was performed according to the Full Analysis Set (FAS), which is defined as all treated subjects with a baseline and post-baseline NMSS measure, and follows the intention-to-treat principle.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to the End of Maintenance in Total Nonmotor Symptoms Scale (NMSS) Score | -19.1 scores on a scale | Standard Deviation 24.2 |
| Rotigotine | Change From Baseline to the End of Maintenance in Total Nonmotor Symptoms Scale (NMSS) Score | -23.1 scores on a scale | Standard Deviation 23.4 |
Comparison: Null hypothesis: mean change in the total Nonmotor Symptoms Scale (NMSS) score is the same for rotigotine- and placebo-treated group.p-value: 0.14795% CI: [-8.43, 1.26]ANCOVA
Secondary
Change From Baseline to the End of Maintenance in Health-related Quality of Life (HRQL) Measured by a 39-item Parkinson's Disease Questionnaire (PDQ-39)
Parkinson's Disease Questionnaire - 39 (PDQ-39) is a self-administered questionnaire. It comprises of 39 questions, relating to eight key areas of health and daily activities, including both Motor and Non-motor symptoms. It is scored on a scale of zero to 100, with lower scores indicating better health and high scores more severe symptoms in change from Baseline to end of Maintenance.
Time frame: From Baseline (Day 1) to end of 12-week Maintenance (Day 84)
Population: This analysis was performed according to the Full Analysis Set (FAS), which is defined as all treated subjects with a baseline and post-baseline NMSS measure, and follows the intention-to-treat principle.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to the End of Maintenance in Health-related Quality of Life (HRQL) Measured by a 39-item Parkinson's Disease Questionnaire (PDQ-39) | -2.6 scores on a scale | Standard Deviation 12.5 |
| Rotigotine | Change From Baseline to the End of Maintenance in Health-related Quality of Life (HRQL) Measured by a 39-item Parkinson's Disease Questionnaire (PDQ-39) | -5.9 scores on a scale | Standard Deviation 10.8 |
p-value: 0.02495% CI: [-5.21, -0.37]ANCOVA
Secondary
Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Attention/Memory,
The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in 9 different domains. Severity (ranges: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) and frequency (ranges: 1 = Rarely (\<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) are rated using a 4-point scale. The final score is derived from multiplying the severity score and the frequency score. A negative change from Baseline to end of Maintenance indicates an improvement in NMSS. The possible min/max final scores per subdomain are calculated as follows: Range of final score per subdomain: 0 - 12 per question multiplied by the number of questions per subdomain: Subdomain Attention/Memory (3 questions): range 0 - 36
Time frame: From Baseline (Day 1) to end of 12-week Maintenance (Day 84)
Population: This analysis was performed according to the Full Analysis Set (FAS), which is defined as all treated subjects with a baseline and post-baseline NMSS measure, and follows the intention-to-treat principle.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Attention/Memory, | -1.3 scores on a scale | Standard Deviation 4.8 |
| Rotigotine | Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Attention/Memory, | -1.5 scores on a scale | Standard Deviation 4.7 |
p-value: 0.99795% CI: [-0.99, 0.99]ANCOVA
Secondary
Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Cardiovascular
The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in 9 different domains. Severity (ranges: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) and frequency (ranges: 1 = Rarely (\<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) are rated using a 4-point scale. The final score is derived from multiplying the severity score and the frequency score. A negative change from Baseline to end of Maintenance indicates an improvement in NMSS. The possible min/max final scores per subdomain are calculated as follows: Range of final score per subdomain: 0 - 12 per question multiplied by the number of questions per subdomain: Subdomain Cardiovascular (2 questions): range 0 - 24
Time frame: From Baseline (Day 1) to end of 12-week Maintenance (Day 84)
Population: This analysis was performed according to the Full Analysis Set (FAS), which is defined as all treated subjects with a baseline and post-baseline NMSS measure, and follows the intention-to-treat principle.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Cardiovascular | -1.2 scores on a scale | Standard Deviation 2.8 |
| Rotigotine | Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Cardiovascular | -1.1 scores on a scale | Standard Deviation 3.2 |
p-value: 0.77395% CI: [-0.67, 0.5]ANCOVA
Secondary
Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Gastrointestinal Tract
The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in 9 different domains. Severity (ranges: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) and frequency (ranges: 1 = Rarely (\<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) are rated using a 4-point scale. The final score is derived from multiplying the severity score and the frequency score. A negative change from Baseline to end of Maintenance indicates an improvement in NMSS. The possible min/max final scores per subdomain are calculated as follows: Range of final score per subdomain: 0 - 12 per question multiplied by the number of questions per subdomain: Subdomain Gastrointestinal tract (3 questions): range 0 - 36
Time frame: From Baseline (Day 1) to end of 12-week Maintenance (Day 84)
Population: This analysis was performed according to the Full Analysis Set (FAS), which is defined as all treated subjects with a baseline and post-baseline NMSS measure, and follows the intention-to-treat principle.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Gastrointestinal Tract | -1.4 scores on a scale | Standard Deviation 3.4 |
| Rotigotine | Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Gastrointestinal Tract | -1.6 scores on a scale | Standard Deviation 3.5 |
p-value: 0.58495% CI: [-0.87, 0.49]ANCOVA
Secondary
Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Miscellaneous
The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in 9 different domains. Severity (ranges: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) and frequency (ranges: 1 = Rarely (\<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) are rated using a 4-point scale. The final score is derived from multiplying the severity score and the frequency score. A negative change from Baseline to end of Maintenance indicates an improvement in NMSS. The possible min/max final scores per subdomain are calculated as follows: Range of final score per subdomain: 0 - 12 per question multiplied by the number of questions per subdomain: Subdomain Miscellaneous (4 questions): range 0 - 48
Time frame: From Baseline (Day 1) to end of 12-week Maintenance (Day 84)
Population: This analysis was performed according to the Full Analysis Set (FAS), which is defined as all treated subjects with a baseline and post-baseline NMSS measure, and follows the intention-to-treat principle.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Miscellaneous | -2.2 scores on a scale | Standard Deviation 4.4 |
| Rotigotine | Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Miscellaneous | -3.2 scores on a scale | Standard Deviation 5.7 |
p-value: 0.04395% CI: [-2.06, -0.03]ANCOVA
Secondary
Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Mood/Cognition
The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in 9 different domains. Severity (ranges: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) and frequency (ranges: 1 = Rarely (\<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) are rated using a 4-point scale. The final score is derived from multiplying the severity score and the frequency score. A negative change from Baseline to end of Maintenance indicates an improvement in NMSS. The possible min/max final scores per subdomain are calculated as follows: Range of final score per subdomain: 0 - 12 per question multiplied by the number of questions per subdomain: Subdomain Mood/Cognition (6 questions): range 0 - 72
Time frame: From Baseline (Day 1) to end of 12-week Maintenance (Day 84)
Population: This analysis was performed according to the Full Analysis Set (FAS), which is defined as all treated subjects with a baseline and post-baseline NMSS measure, and follows the intention-to-treat principle.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Mood/Cognition | -5.1 scores on a scale | Standard Deviation 10 |
| Rotigotine | Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Mood/Cognition | -6.6 scores on a scale | Standard Deviation 11 |
p-value: 0.04795% CI: [-3.59, -0.02]ANCOVA
Secondary
Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Perception/Hallucinations
The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in 9 different domains. Severity (ranges: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) and frequency (ranges: 1 = Rarely (\<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) are rated using a 4-point scale. The final score is derived from multiplying the severity score and the frequency score. A negative change from Baseline to end of Maintenance indicates an improvement in NMSS. The possible min/max final scores per subdomain are calculated as follows: Range of final score per subdomain: 0 - 12 per question multiplied by the number of questions per subdomain: Subdomain Perception/Hallucinations (3 questions): range 0 - 36
Time frame: From Baseline (Day 1) to end of 12-week Maintenance (Day 84)
Population: This analysis was performed according to the Full Analysis Set (FAS), which is defined as all treated subjects with a baseline and post-baseline NMSS measure, and follows the intention-to-treat principle.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Perception/Hallucinations | -0.2 scores on a scale | Standard Deviation 1.8 |
| Rotigotine | Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Perception/Hallucinations | -0.2 scores on a scale | Standard Deviation 1.6 |
p-value: 0.60195% CI: [-0.22, 0.37]ANCOVA
Secondary
Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Sexual Function
The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in 9 different domains. Severity (ranges: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) and frequency (ranges: 1 = Rarely (\<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) are rated using a 4-point scale. The final score is derived from multiplying the severity score and the frequency score. A negative change from Baseline to end of Maintenance indicates an improvement in NMSS. The possible min/max final scores per subdomain are calculated as follows: Range of final score per subdomain: 0 - 12 per question multiplied by the number of questions per subdomain: Subdomain Sexual function (2 questions): range 0 - 24
Time frame: From Baseline (Day 1) to end of 12-week Maintenance (Day 84)
Population: This analysis was performed according to the Full Analysis Set (FAS), which is defined as all treated subjects with a baseline and post-baseline NMSS measure, and follows the intention-to-treat principle.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Sexual Function | -1.2 scores on a scale | Standard Deviation 4.2 |
| Rotigotine | Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Sexual Function | -1.1 scores on a scale | Standard Deviation 4.3 |
p-value: 0.88995% CI: [-0.81, 0.94]ANCOVA
Secondary
Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Sleep/Fatigue
The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in 9 different domains. Severity (ranges: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) and frequency (ranges: 1 = Rarely (\<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) are rated using a 4-point scale. The final score is derived from multiplying the severity score and the frequency score. A negative change from Baseline to end of Maintenance indicates an improvement in NMSS. The possible min/max final scores per subdomain are calculated as follows: Range of final score per subdomain: 0 - 12 per question multiplied by the number of questions per subdomain: Subdomain Sleep/Fatigue (4 questions): range 0-48
Time frame: From Baseline (Day 1) to end of 12-week Maintenance (Day 84)
Population: This analysis was performed according to the Full Analysis Set (FAS), which is defined as all treated subjects with a baseline and post-baseline NMSS measure, and follows the intention-to-treat principle.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Sleep/Fatigue | -3.9 scores on a scale | Standard Deviation 5.9 |
| Rotigotine | Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Sleep/Fatigue | -5.4 scores on a scale | Standard Deviation 7.8 |
p-value: 0.12295% CI: [-2.41, 0.29]ANCOVA
Secondary
Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Urinary
The Nonmotor Symptoms Scale (NMSS) is a validated tool for rating frequency and severity of nonmotor symptoms in Parkinson's Disease (PD). The severity and frequency of the subject's nonmotor symptoms is assessed by the investigator in 9 different domains. Severity (ranges: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) and frequency (ranges: 1 = Rarely (\<1/wk), 2 = Often (1/wk), 3 = Frequent (several times per week), 4 = Very Frequent (daily or all the time) are rated using a 4-point scale. The final score is derived from multiplying the severity score and the frequency score. A negative change from Baseline to end of Maintenance indicates an improvement in NMSS. The possible min/max final scores per subdomain are calculated as follows: Range of final score per subdomain: 0 - 12 per question multiplied by the number of questions per subdomain: Subdomain Urinary (3 questions): range 0 - 36
Time frame: From Baseline (Day 1) to end of 12-week Maintenance (Day 84)
Population: This analysis was performed according to the Full Analysis Set (FAS), which is defined as all treated subjects with a baseline and post-baseline NMSS measure, and follows the intention-to-treat principle.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Urinary | -2.7 scores on a scale | Standard Deviation 6.6 |
| Rotigotine | Change From Baseline to the End of Maintenance in the Nonmotor Symptoms Scale Score: Subdomain Urinary | -2.4 scores on a scale | Standard Deviation 6 |
p-value: 0.53695% CI: [-0.84, 1.6]ANCOVA
Secondary
Change From Baseline to the End of Maintenance in Total Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score
The Unified Parkinson's Disease Rating Scale (UPDRS) Part III is a scale for the assessment of function in Parkinson's Disease. UPDRS Part III measures Motor Function. It consists of 14 items with 27 questions, each ranging from 0 to 4. The sum score for the UPDRS Part III ranges from 0 to 108. A higher score indicates greater disability. A negative change from Baseline to end of Maintenance score indicates improvement.
Time frame: From Baseline (Day 1) to end of 12-week Maintenance (Day 84)
Population: This analysis was performed according to the Full Analysis Set (FAS), which is defined as all treated subjects with a baseline and post-baseline NMSS measure, and follows the intention-to-treat principle.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to the End of Maintenance in Total Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score | -3.6 scores on a scale | Standard Deviation 8.3 |
| Rotigotine | Change From Baseline to the End of Maintenance in Total Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score | -5.7 scores on a scale | Standard Deviation 8 |
p-value: 0.00295% CI: [-4.27, -0.92]ANCOVA