Idiopathic Parkinson's Disease
Conditions
Keywords
Rotigotine, Neupro phase 3, Advanced-stage, Idiopathic Parkinson's Disease
Brief summary
The primary objective of this study was to demonstrate that Rotigotine transdermal patch is efficacious in Chinese subjects with advanced-stage Idiopathic Parkinson's Disease as an adjuvant therapy.
Detailed description
The study included a maximum 4-week Screening Period, a maximum 7-week Titration Period for advanced-stage Parkinson's disease, 12-week Maintenance Period, a maximum 12-day De-escalation Period for advanced-stage Parkinson's Disease and 30-day Safety Follow-Up Period. The maximum study duration for an individual subject with advanced-stage Parkinson's disease was 27 weeks.
Interventions
DRUGRotigotine
Transdermal Patch Content: 4 mg /24 h (20 cm\^2), 6 mg /24 h (30 cm\^2), 8 mg /24 h (40 cm\^2) For advanced-stage Parkinson's Disease, subjects received Rotigotine patches in escalating weekly dose (starting with daily doses 4 mg/24 h to 16 mg/24 h) for a maximum 7-week Titration Period, then 12 week maintenance period
DRUGPlacebo Patch
Transdermal Patch Size: 20 cm\^2, 30 cm\^2, 40 cm\^2 Subjects randomized to placebo received matching placebo patches
DRUGL-dopa
Subject must be on a stable dose of L-dopa (either short-acting or sustained release \[in combination with benserazide or carbidopa\]) of at least 200 mg/day, administered in at least 2 intakes, for at least 28 days prior to Baseline.
Sponsors
UCB Trading (Shanghai) Co. Ltd.
UCB Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Inclusion Criteria: * An Independent Ethics Committee (IEC)-approved written informed consent is signed and dated by the subject or by the legal representative * Subject/legal representative is considered reliable and capable of adhering to the protocol (eg, able to understand and complete diaries), visit schedule, and medication application according to the judgment of the investigator * Subject has Idiopathic Parkinson's Disease of more than 3 years' duration, defined by the cardinal sign, Bradykinesia, plus the presence of at least 1 of the following: resting tremor, rigidity, or impairment of postural reflexes, and without any other known or suspected cause of Parkinsonism * The investigator must observe the subject in both the 'on' and 'off' state and determine that the subject is Hoehn & Yahr stage 2 through 4 in both the 'on' and 'off' state * Subject is male or female and aged ≥30 years at Screening (Visit 1) * Subject has a Mini Mental State Examination (MMSE) score of ≥25 at Screening (Visit 1) * Subject must be on a stable dose of L-dopa (either short-acting or sustained release \[in combination with Benserazide or Carbidopa\]) of at least 200 mg/day, administered in at least 2 intakes, for at least 28 days prior to Baseline (Visit 2) * Subject is not adequately controlled on a L-dopa dose (in combination with Benserazide or Carbidopa) which was judged by the treating physician to be optimal * Subject must be willing and able to accurately complete a subject diary on designated days (with assistance from caregivers, if required), recording periods when they are 'on without troublesome Dyskinesia', 'on with troublesome Dyskinesia', 'off', and sleeping * As part of the Screening (pretreatment) assessments, the subject must complete a diary over a period of 6 days, with 4 of the 6 diaries being 'valid' as determined by the investigator (see Section 9.1.1) * It must be clear to the investigator that the subject is able to differentiate between the 'on' and 'off' state and the 'valid' diaries confirm that the subject has an average of ≥2.5 h/day spent in the 'off' state * If the subject is receiving an Anticholinergic agent (eg, Benztropine, Trihexyphenidyl, Parsitan, Procyclidine, Biperiden), a monoamine oxidase (MAO)-B inhibitor (eg, Selegiline), and/or an N-methyl-d-aspartate (NMDA) antagonist (eg, Amantadine), he/she must have been on a stable dose for at least 28 days prior to Baseline (Visit 2) and be maintained on that dose for the duration of the study * Subject must be on a stable dose of all anti-Parkinsonian medications for at least 20 days prior to completing the 6 Baseline diaries
Exclusion criteria
* Subject has previously participated in this study or subject has previously received the study medication under investigation in this study * Subject is participating in another study of an investigational drug or has done so within 28 days prior to the Baseline Visit (Visit 2) * Subject has a history of significant skin hypersensitivity to adhesive or other transdermal preparations, or recent unresolved contact dermatitis * Subject has a lifetime history of suicide attempt (including an actual attempt, interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6 months as indicated by a positive response ('Yes') to either Question 4 or Question 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening (Visit 1) * Subject has atypical Parkinson's syndrome(s) due to drugs (eg, Metoclopramide, Flunarizine), Metabolic Neurogenetic Disorders (eg, Wilson's Disease), Encephalitis, Cerebrovascular Disease, or Degenerative Disease (eg, Progressive Supranuclear Palsy) * Subject has a history of Pallidotomy, Thalamotomy, deep brain stimulation, or fetal tissue transplant * Subject has dementia, active psychosis or hallucinations, or severe depression * Subject is receiving therapy with a Dopamine agonist either concurrently or has done so within 28 days prior to the Baseline Visit (Visit 2) * Subject is receiving therapy with 1 of the following drugs either concurrently or within 28 days prior to Baseline (Visit 2): Alpha-methyl dopa, Metoclopramide, Reserpine, Neuroleptics (except specific atypical neuroleptics: Olanzapine, Ziprasidone, Aripiprazole, Clozapine, quetiapine), MAO-A inhibitors, Methylphenidate, or Amphetamine * Subject is currently receiving central nervous system (CNS) active therapy (eg, sedatives, hypnotics, antidepressants, anxiolytics), unless the dose has been stable for at least 28 days prior to Baseline (Visit 2) and is likely to remain stable for the duration of the study * Subject has a current diagnosis of Epilepsy, has a history of seizures as an adult, has a history of stroke, or has had a transient ischemic attack within 1 year prior to Screening (Visit 1) * Subject has clinically relevant hepatic dysfunction (as defined as a total bilirubin \>2.0 mg/dL, or Alanine Aminotransferase (ALT) and/or Aspartate Aminotransferase (AST) \>2 times the upper limit of the reference range) * Subject has clinically relevant renal dysfunction (serum creatinine \>2.0 mg/dL \[\>178 μmol/L\]) * Subject has clinically relevant cardiac dysfunction (any cardiac disorder which in the opinion of the investigator would put the subject at risk of clinically relevant arrhythmia) and/or myocardial infarction within the last 12 months * Subject has a QT interval corrected for heart rate according to Bazett's formula (QTcB) of ≥500 ms at Screening (Visit 1) * Subject has a history of only symptomatic (not asymptomatic) orthostatic hypotension, with a decrease of systolic blood pressure (SBP) from supine to standing position of ≥2 0 mmHg or of ≥10 mmHg in DBP after 1 or 3 minutes within 28 days prior to Baseline (Visit 2), or SBP \<105 mmHg at study entry 17. Subject has evidence of an impulse control disorder (ICD) at Screening (Visit 1) * Subject has a history of known intolerance/hypersensitivity to the following Antiemetics: Domperidone, Trimethobenzamide, Ondansetron, Tropisetron, Granisetron, and Glycopyrrolate * Subject has a history of chronic alcohol or drug abuse within the last 5 years * Subject is pregnant or nursing, or is of childbearing potential but (i) not surgically sterile or (ii) not using adequate birth control methods (including at least a double barrier method) or (iii) not sexually abstinent or (iv) not at least 2 years post-menopausal * Subject has any other clinically relevant medical condition, psychiatric condition, or laboratory abnormality which would, in the judgment of the investigator, interfere with the subject's ability to participate in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change in Absolute Time Spent 'Off' From Baseline to the End of Double-blind Maintenance Period | From Baseline (Week 0) to end of Maintenance Period (up to Week 12) | A subject has been considered off when he/she began to lose the optimum effects of anti-Parkinson's medication. A negative mean indicates a reduction of the time off during the conduct of the study |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Absolute Time Spent Off From Baseline to the End of Double-blind Maintenance Period | From Baseline (Week 0) to end of Maintenance Period (up to Week 12) | A subject has been considered off when he/she began to lose the optimum effects of anti-Parkinson's medication. Absolute time off is defined as the mean number of hours marked off during a 24-hour period from all valid daily diary cards. |
| Percent Change in Relative Time Spent Off From Baseline to the End of Double-blind Maintenance Period | From Baseline (Week 0) to end of Maintenance Period (up to Week 12) | A subject has been considered off when he/she began to lose the optimum effects of anti-Parkinson's medication. Relative time spent off will be calculated in two stages. Each valid daily diary will have an associated relative time off calculated as relative time off for day = 100\*\[total absolute time off for day/ absolute time awake for day\]. Relative time spent off is then calculated by averaging the daily relative time off for the valid days of that visit. |
| Change in Absolute Time Spent on From Baseline to the End of Double-blind Maintenance Period | From Baseline (Week 0) to end of Maintenance Period (up to Week 12) | A subject has been considered on when he/she felt the effects of L-dopa. The subject recorded the exact time of L-dopa intake and his/her status at the time of the L-dopa dose. In instances when the subject was 'off' when taking his/her L-dopa, he/she recorded the exact time their status changed to 'on'. Absolute time on is defined as the mean number of hours marked on during a 24-hour period from all valid daily diary cards. |
| Change in Relative Time Spent on From Baseline to the End of Double-blind Maintenance Period | From Baseline (Week 0) to end of Maintenance Period (up to Week 12) | A subject has been considered on when he/she felt the effects of L-dopa. The subject recorded the exact time of L-dopa intake and his/her status at the time of the L-dopa dose. In instances when the subject was off when taking his/her L-dopa, he/she recorded the exact time their status changed to on. Relative time spent on will be calculated in two stages. Each valid daily diary will have an associated relative time on calculated as relative time on for day = 100\*\[total absolute time on for day/ absolute time awake for day\]. Relative time spent on is then calculated by averaging the daily relative time on for the valid days of that visit. |
| Percent Change in Absolute Time Spent on From Baseline to the End of Double-blind Maintenance Period | From Baseline (Week 0) to end of Maintenance Period (up to Week 12) | A subject has been considered on when he/she felt the effects of L-dopa. The subject recorded the exact time of L-dopa intake and his/her status at the time of the L-dopa dose. In instances when the subject was 'off' when taking his/her L-dopa, he/she recorded the exact time their status changed to 'on'. Note for percent change calculations: when absolute time at Baseline was 0 hours, the absolute Baseline value was assumed to be 1 minute for calculation purposes. |
| Percentage of Responders From Baseline to the End of the Doubleblind Maintenance Period | From Baseline (Week 0) to end of Maintenance Period (up to Week 12) | A Responder is defined as a subject with an ≥ 30 % decrease in absolute time spent 'off' |
| Change in the Number of Off Periods From Baseline to the End of Double-blind Maintenance Period | From Baseline (Week 0) to end of Maintenance Period (up to Week 12) | A subject has been considered off when he/she began to lose the optimum effects of anti-Parkinson's medication. |
| Change in Status of the Subject (on) After Wake-up With Troublesome Dyskinesia From Baseline to the End of Double-blind Maintenance Period | From Baseline (Week 0) to end of Maintenance Period (up to Week 12) | A subject has been considered on when he/she felt the effects of L-dopa. The subject recorded the exact time of L-dopa intake and his/her status at the time of the L-dopa dose. In instances when the subject was 'off' when taking his/her L-dopa, he/she recorded the exact time their status changed to 'on'. The percentage of days from Baseline to the end of the double-blind Maintenance Period in which the subject woke in the on with troublesome dyskinesia state is presented below. |
| Change in Status of the Subject (on) After Wake-up Without Troublesome Dyskinesia From Baseline to the End of Double-blind Maintenance Period | From Baseline (Week 0) to end of Maintenance Period (up to Week 12) | A subject has been considered on when he/she felt the effects of L-dopa. The subject recorded the exact time of L-dopa intake and his/her status at the time of the L-dopa dose. In instances when the subject was 'off' when taking his/her L-dopa, he/she recorded the exact time their status changed to 'on'. The percentage of days from Baseline to the end of the double-blind Maintenance Period in which the subject woke in the on without troublesome dyskinesia state is presented below. |
| Change in Status of the Subject (Off) After Wake-up From Baseline to the End of Double-blind Maintenance Period | From Baseline (Week 0) to end of Maintenance Period (up to Week 12) | A subject has been considered off when he/she began to lose the optimum effects of anti-Parkinson's medication. The percentage of days from Baseline to the end of the double-blind Maintenance Period in which the subject woke in the off state is presented below. |
| Change in Unified Parkinson's Disease Rating Scale (UPDRS Part III Motor Examination) During on Periods From Baseline to the End of Double-blind Maintenance Period | From Baseline (Week 0) to end of Maintenance Period (up to Week 12) | The UPDRS Part III (motor subscale) assessment consists of 27 questions, measured on a 5-Point scale (0 to 4). The sum score is calculated as sum of these 27 individual questions. This score ranges from 0 to 108, higher scores denote greater disability. A subject has been considered on when he/she felt the effects of L-dopa. The subject recorded the exact time of L-dopa intake and his/her status at the time of the L-dopa dose. In instances when the subject was 'off' when taking his/her L-dopa, he/she recorded the exact time their status changed to 'on'. |
| Percent Change in Relative Time Spent on From Baseline to the End of Double-blind Maintenance Period | From Baseline (Week 0) to end of Maintenance Period (up to Week 12) | A subject has been considered on when he/she felt the effects of L-dopa. The subject recorded the exact time of L-dopa intake and his/her status at the time of the L-dopa dose. In instances when the subject was off when taking his/her L-dopa, he/she recorded the exact time their status changed to on. Note for percent change calculations: when relative time at Baseline was 0%, the relative Baseline value was assumed to be 0.1 for calculation purposes. Relative time spent on will be calculated in two stages. Each valid daily diary will have an associated relative time on calculated as relative time on for day = 100\*\[total absolute time on for day/ absolute time awake for day\]. Relative time spent on is then calculated by averaging the daily relative time on for the valid days of that visit. |
Countries
China
Participant flow
Recruitment details
This multicenter, randomized, double-blind, parallel-group, placebo-controlled study started recruiting in August 2012.
Pre-assignment details
Participant Flow refers to the Safety Set (SS), consisting of all randomized subjects who received at least 1 dose of study medication.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Subjects randomized to placebo received matching placebo patches. | 172 |
| Rotigotine Subjects received rotigotine in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h or matching placebo) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h was achieved. Each dose level was maintained for 1 week. | 174 |
| Total Title | 346 |
| Total | 692 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 7 | 8 |
| Overall Study | Compliance is not well | 1 | 0 |
| Overall Study | Inclusion Criteria Deviation | 1 | 0 |
| Overall Study | Lack of Efficacy | 2 | 0 |
| Overall Study | Withdrawal by Subject | 10 | 6 |
Baseline characteristics
| Characteristic | Total Title | Placebo | Rotigotine |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 139 Participants | 76 Participants | 63 Participants |
| Age, Categorical Between 18 and 65 years | 207 Participants | 96 Participants | 111 Participants |
| Age, Continuous mean (standard deviation) | 62.2 years STANDARD_DEVIATION 8.9 | 62.8 years STANDARD_DEVIATION 9.1 | 61.7 years STANDARD_DEVIATION 8.8 |
| Sex: Female, Male Female | 143 Participants | 62 Participants | 81 Participants |
| Sex: Female, Male Male | 203 Participants | 110 Participants | 93 Participants |
| Weight | 61.10 kg STANDARD_DEVIATION 10.18 | 61.83 kg STANDARD_DEVIATION 10.18 | 60.38 kg STANDARD_DEVIATION 10.15 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 24 / 172 | 54 / 174 |
| serious Total, serious adverse events | 6 / 172 | 6 / 174 |
Outcome results
Primary
Absolute Change in Absolute Time Spent 'Off' From Baseline to the End of Double-blind Maintenance Period
A subject has been considered off when he/she began to lose the optimum effects of anti-Parkinson's medication. A negative mean indicates a reduction of the time off during the conduct of the study
Time frame: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)
Population: The Full Analysis Set (FAS) consisted of all subjects who have been randomized, received at least 1 dose of study medication, had a valid Baseline primary efficacy measurement, and had at least 1 valid post-Baseline primary efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Full Analysis Set (Placebo Treated Subjects) | Absolute Change in Absolute Time Spent 'Off' From Baseline to the End of Double-blind Maintenance Period | -1.13 hours | Standard Deviation 3.2 |
| Full Analysis Set (Rotigotine Treated Subjects) | Absolute Change in Absolute Time Spent 'Off' From Baseline to the End of Double-blind Maintenance Period | -2.36 hours | Standard Deviation 2.83 |
Comparison: Estimate of treatment effect has been obtained from an analysis of covariance (ANCOVA) model to the change from Baseline value in absolute time spent off. The ANCOVA model contained treatment and (pooled) site as factors and Baseline off time as covariate. A last observation carried forward (LOCF) imputation approach was used for missing values (during both Titration and Maintenance Periods) for the primary efficacy analysis.p-value: =0.000295% CI: [-1.83, -0.57]ANCOVA
Secondary
Change in Absolute Time Spent on From Baseline to the End of Double-blind Maintenance Period
A subject has been considered on when he/she felt the effects of L-dopa. The subject recorded the exact time of L-dopa intake and his/her status at the time of the L-dopa dose. In instances when the subject was 'off' when taking his/her L-dopa, he/she recorded the exact time their status changed to 'on'. Absolute time on is defined as the mean number of hours marked on during a 24-hour period from all valid daily diary cards.
Time frame: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)
Population: The Full Analysis Set (FAS) consisted of all subjects who have been randomized, received at least 1 dose of study medication, had a valid Baseline primary efficacy measurement, and had at least 1 valid post-Baseline primary efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Full Analysis Set (Placebo Treated Subjects) | Change in Absolute Time Spent on From Baseline to the End of Double-blind Maintenance Period | 0.94 hours | Standard Deviation 3.08 |
| Full Analysis Set (Rotigotine Treated Subjects) | Change in Absolute Time Spent on From Baseline to the End of Double-blind Maintenance Period | 2.05 hours | Standard Deviation 2.98 |
Secondary
Change in Relative Time Spent on From Baseline to the End of Double-blind Maintenance Period
A subject has been considered on when he/she felt the effects of L-dopa. The subject recorded the exact time of L-dopa intake and his/her status at the time of the L-dopa dose. In instances when the subject was off when taking his/her L-dopa, he/she recorded the exact time their status changed to on. Relative time spent on will be calculated in two stages. Each valid daily diary will have an associated relative time on calculated as relative time on for day = 100\*\[total absolute time on for day/ absolute time awake for day\]. Relative time spent on is then calculated by averaging the daily relative time on for the valid days of that visit.
Time frame: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)
Population: The Full Analysis Set (FAS) consisted of all subjects who have been randomized, received at least 1 dose of study medication, had a valid Baseline primary efficacy measurement, and had at least 1 valid post-Baseline primary efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Full Analysis Set (Placebo Treated Subjects) | Change in Relative Time Spent on From Baseline to the End of Double-blind Maintenance Period | 6.78 hours | Standard Deviation 19.61 |
| Full Analysis Set (Rotigotine Treated Subjects) | Change in Relative Time Spent on From Baseline to the End of Double-blind Maintenance Period | 14.49 hours | Standard Deviation 18.7 |
Secondary
Change in Status of the Subject (Off) After Wake-up From Baseline to the End of Double-blind Maintenance Period
A subject has been considered off when he/she began to lose the optimum effects of anti-Parkinson's medication. The percentage of days from Baseline to the end of the double-blind Maintenance Period in which the subject woke in the off state is presented below.
Time frame: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)
Population: The Full Analysis Set (FAS) consisted of all subjects who have been randomized, received at least 1 dose of study medication, had a valid Baseline primary efficacy measurement, and had at least 1 valid post-Baseline primary efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Full Analysis Set (Placebo Treated Subjects) | Change in Status of the Subject (Off) After Wake-up From Baseline to the End of Double-blind Maintenance Period | -10.34 percentage of days | Standard Deviation 47.81 |
| Full Analysis Set (Rotigotine Treated Subjects) | Change in Status of the Subject (Off) After Wake-up From Baseline to the End of Double-blind Maintenance Period | -21.14 percentage of days | Standard Deviation 48.49 |
Secondary
Change in Status of the Subject (on) After Wake-up Without Troublesome Dyskinesia From Baseline to the End of Double-blind Maintenance Period
A subject has been considered on when he/she felt the effects of L-dopa. The subject recorded the exact time of L-dopa intake and his/her status at the time of the L-dopa dose. In instances when the subject was 'off' when taking his/her L-dopa, he/she recorded the exact time their status changed to 'on'. The percentage of days from Baseline to the end of the double-blind Maintenance Period in which the subject woke in the on without troublesome dyskinesia state is presented below.
Time frame: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)
Population: The Full Analysis Set (FAS) consisted of all subjects who have been randomized, received at least 1 dose of study medication, had a valid Baseline primary efficacy measurement, and had at least 1 valid post-Baseline primary efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Full Analysis Set (Placebo Treated Subjects) | Change in Status of the Subject (on) After Wake-up Without Troublesome Dyskinesia From Baseline to the End of Double-blind Maintenance Period | 7.92 percentage of days | Standard Deviation 43.29 |
| Full Analysis Set (Rotigotine Treated Subjects) | Change in Status of the Subject (on) After Wake-up Without Troublesome Dyskinesia From Baseline to the End of Double-blind Maintenance Period | 22.55 percentage of days | Standard Deviation 45.41 |
Secondary
Change in Status of the Subject (on) After Wake-up With Troublesome Dyskinesia From Baseline to the End of Double-blind Maintenance Period
A subject has been considered on when he/she felt the effects of L-dopa. The subject recorded the exact time of L-dopa intake and his/her status at the time of the L-dopa dose. In instances when the subject was 'off' when taking his/her L-dopa, he/she recorded the exact time their status changed to 'on'. The percentage of days from Baseline to the end of the double-blind Maintenance Period in which the subject woke in the on with troublesome dyskinesia state is presented below.
Time frame: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)
Population: The Full Analysis Set (FAS) consisted of all subjects who have been randomized, received at least 1 dose of study medication, had a valid Baseline primary efficacy measurement, and had at least 1 valid post-Baseline primary efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Full Analysis Set (Placebo Treated Subjects) | Change in Status of the Subject (on) After Wake-up With Troublesome Dyskinesia From Baseline to the End of Double-blind Maintenance Period | 2.42 percentage of days | Standard Deviation 21.7 |
| Full Analysis Set (Rotigotine Treated Subjects) | Change in Status of the Subject (on) After Wake-up With Troublesome Dyskinesia From Baseline to the End of Double-blind Maintenance Period | 1.24 percentage of days | Standard Deviation 16.9 |
Secondary
Change in the Number of Off Periods From Baseline to the End of Double-blind Maintenance Period
A subject has been considered off when he/she began to lose the optimum effects of anti-Parkinson's medication.
Time frame: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)
Population: The Full Analysis Set (FAS) consisted of all subjects who have been randomized, received at least 1 dose of study medication, had a valid Baseline primary efficacy measurement, and had at least 1 valid post-Baseline primary efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Full Analysis Set (Placebo Treated Subjects) | Change in the Number of Off Periods From Baseline to the End of Double-blind Maintenance Period | -0.61 Number of 'off' Periods | Standard Deviation 1.59 |
| Full Analysis Set (Rotigotine Treated Subjects) | Change in the Number of Off Periods From Baseline to the End of Double-blind Maintenance Period | -0.89 Number of 'off' Periods | Standard Deviation 1.32 |
Secondary
Change in Unified Parkinson's Disease Rating Scale (UPDRS Part III Motor Examination) During on Periods From Baseline to the End of Double-blind Maintenance Period
The UPDRS Part III (motor subscale) assessment consists of 27 questions, measured on a 5-Point scale (0 to 4). The sum score is calculated as sum of these 27 individual questions. This score ranges from 0 to 108, higher scores denote greater disability. A subject has been considered on when he/she felt the effects of L-dopa. The subject recorded the exact time of L-dopa intake and his/her status at the time of the L-dopa dose. In instances when the subject was 'off' when taking his/her L-dopa, he/she recorded the exact time their status changed to 'on'.
Time frame: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)
Population: The Full Analysis Set (FAS) consisted of all subjects who have been randomized, received at least 1 dose of study medication, had a valid Baseline primary efficacy measurement, and had at least 1 valid post-Baseline primary efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Full Analysis Set (Placebo Treated Subjects) | Change in Unified Parkinson's Disease Rating Scale (UPDRS Part III Motor Examination) During on Periods From Baseline to the End of Double-blind Maintenance Period | -3.6 units on a scale | Standard Deviation 9.8 |
| Full Analysis Set (Rotigotine Treated Subjects) | Change in Unified Parkinson's Disease Rating Scale (UPDRS Part III Motor Examination) During on Periods From Baseline to the End of Double-blind Maintenance Period | -10.4 units on a scale | Standard Deviation 10.4 |
Secondary
Percentage of Responders From Baseline to the End of the Doubleblind Maintenance Period
A Responder is defined as a subject with an ≥ 30 % decrease in absolute time spent 'off'
Time frame: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)
Population: The Full Analysis Set (FAS) consisted of all subjects who have been randomized, received at least 1 dose of study medication, had a valid Baseline primary efficacy measurement, and had at least 1 valid post-Baseline primary efficacy measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Full Analysis Set (Placebo Treated Subjects) | Percentage of Responders From Baseline to the End of the Doubleblind Maintenance Period | 36.9 percentage of participants |
| Full Analysis Set (Rotigotine Treated Subjects) | Percentage of Responders From Baseline to the End of the Doubleblind Maintenance Period | 48.8 percentage of participants |
Secondary
Percent Change in Absolute Time Spent Off From Baseline to the End of Double-blind Maintenance Period
A subject has been considered off when he/she began to lose the optimum effects of anti-Parkinson's medication. Absolute time off is defined as the mean number of hours marked off during a 24-hour period from all valid daily diary cards.
Time frame: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)
Population: The Full Analysis Set (FAS) consisted of all subjects who have been randomized, received at least 1 dose of study medication, had a valid Baseline primary efficacy measurement, and had at least 1 valid post-Baseline primary efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Full Analysis Set (Placebo Treated Subjects) | Percent Change in Absolute Time Spent Off From Baseline to the End of Double-blind Maintenance Period | -15.0 percent change | Standard Deviation 56.56 |
| Full Analysis Set (Rotigotine Treated Subjects) | Percent Change in Absolute Time Spent Off From Baseline to the End of Double-blind Maintenance Period | -36.03 percent change | Standard Deviation 43.03 |
Secondary
Percent Change in Absolute Time Spent on From Baseline to the End of Double-blind Maintenance Period
A subject has been considered on when he/she felt the effects of L-dopa. The subject recorded the exact time of L-dopa intake and his/her status at the time of the L-dopa dose. In instances when the subject was 'off' when taking his/her L-dopa, he/she recorded the exact time their status changed to 'on'. Note for percent change calculations: when absolute time at Baseline was 0 hours, the absolute Baseline value was assumed to be 1 minute for calculation purposes.
Time frame: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)
Population: The Full Analysis Set (FAS) consisted of all subjects who have been randomized, received at least 1 dose of study medication, had a valid Baseline primary efficacy measurement, and had at least 1 valid post-Baseline primary efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Full Analysis Set (Placebo Treated Subjects) | Percent Change in Absolute Time Spent on From Baseline to the End of Double-blind Maintenance Period | 13.53 percent change | Standard Deviation 42.74 |
| Full Analysis Set (Rotigotine Treated Subjects) | Percent Change in Absolute Time Spent on From Baseline to the End of Double-blind Maintenance Period | 368.55 percent change | Standard Deviation 4446.55 |
Secondary
Percent Change in Relative Time Spent Off From Baseline to the End of Double-blind Maintenance Period
A subject has been considered off when he/she began to lose the optimum effects of anti-Parkinson's medication. Relative time spent off will be calculated in two stages. Each valid daily diary will have an associated relative time off calculated as relative time off for day = 100\*\[total absolute time off for day/ absolute time awake for day\]. Relative time spent off is then calculated by averaging the daily relative time off for the valid days of that visit.
Time frame: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)
Population: The Full Analysis Set (FAS) consisted of all subjects who have been randomized, received at least 1 dose of study medication, had a valid Baseline primary efficacy measurement, and had at least 1 valid post-Baseline primary efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Full Analysis Set (Placebo Treated Subjects) | Percent Change in Relative Time Spent Off From Baseline to the End of Double-blind Maintenance Period | -14.86 percent change | Standard Deviation 53.26 |
| Full Analysis Set (Rotigotine Treated Subjects) | Percent Change in Relative Time Spent Off From Baseline to the End of Double-blind Maintenance Period | -34.97 percent change | Standard Deviation 43.87 |
Secondary
Percent Change in Relative Time Spent on From Baseline to the End of Double-blind Maintenance Period
A subject has been considered on when he/she felt the effects of L-dopa. The subject recorded the exact time of L-dopa intake and his/her status at the time of the L-dopa dose. In instances when the subject was off when taking his/her L-dopa, he/she recorded the exact time their status changed to on. Note for percent change calculations: when relative time at Baseline was 0%, the relative Baseline value was assumed to be 0.1 for calculation purposes. Relative time spent on will be calculated in two stages. Each valid daily diary will have an associated relative time on calculated as relative time on for day = 100\*\[total absolute time on for day/ absolute time awake for day\]. Relative time spent on is then calculated by averaging the daily relative time on for the valid days of that visit.
Time frame: From Baseline (Week 0) to end of Maintenance Period (up to Week 12)
Population: The Full Analysis Set (FAS) consisted of all subjects who have been randomized, received at least 1 dose of study medication, had a valid Baseline primary efficacy measurement, and had at least 1 valid post-Baseline primary efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Full Analysis Set (Placebo Treated Subjects) | Percent Change in Relative Time Spent on From Baseline to the End of Double-blind Maintenance Period | 14.99 percent change | Standard Deviation 42.6 |
| Full Analysis Set (Rotigotine Treated Subjects) | Percent Change in Relative Time Spent on From Baseline to the End of Double-blind Maintenance Period | 616.80 percent change | Standard Deviation 7667.58 |