Rotigotine Versus Placebo, A Study To Evaluate The Efficacy In Advanced Stage Idiopathic Parkinson's Disease Patients
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Rotigotine Rotigotine, daily doses, treatment group |
Drug: Rotigotine
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
Drug: L-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.
Other Names:
|
| Placebo Comparator: Placebo Placebo, daily doses, placebo group |
Drug: Placebo Patch
Transdermal Patch
Size:
20 cm^2, 30 cm^2, 40 cm^2
Subjects randomized to placebo received matching placebo patches
Drug: L-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.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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'
- 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.
- 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.
- 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'.
Eligibility Criteria
Criteria
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
Exclusion Criteria:
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Sp1037 001 | Beijing | China | ||
| 2 | Sp1037 002 | Beijing | China | ||
| 3 | Sp1037 019 | Beijing | China | ||
| 4 | Sp1037 025 | Beijing | China | ||
| 5 | Sp1037 017 | Changchun | China | ||
| 6 | Sp1037 007 | Chengdu | China | ||
| 7 | Sp1037 027 | Chengdu | China | ||
| 8 | Sp1037 021 | Fuzhou | China | ||
| 9 | Sp1037 010 | Guangzhou | China | ||
| 10 | Sp1037 011 | Guangzhou | China | ||
| 11 | Sp1037 014 | Guangzhou | China | ||
| 12 | Sp1037 015 | Guangzhou | China | ||
| 13 | Sp1037 005 | Hangzhou | China | ||
| 14 | Sp1037 013 | Hangzhou | China | ||
| 15 | Sp1037 018 | Hangzhou | China | ||
| 16 | Sp1037 023 | Jinan | China | ||
| 17 | Sp1037 003 | Shanghai | China | ||
| 18 | Sp1037 004 | Shanghai | China | ||
| 19 | Sp1037 009 | Shanghai | China | ||
| 20 | Sp1037 008 | Suzhou | China | ||
| 21 | Sp1037 016 | Tianjin | China | ||
| 22 | Sp1037 006 | Wuhan | China | ||
| 23 | Sp1037 022 | Wuhan | China | ||
| 24 | Sp1037 024 | Wuhan | China |
Sponsors and Collaborators
- UCB Pharma
- UCB Trading (Shanghai) Co. Ltd.
Investigators
- Study Director: UCB Clinical Trial Call Center, 1 877 822 9493
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SP1037
Study Results
Participant Flow
| Recruitment Details | This multicenter, randomized, double-blind, parallel-group, placebo-controlled study started recruiting in August 2012. |
|---|---|
| Pre-assignment Detail | Participant Flow refers to the Safety Set (SS), consisting of all randomized subjects who received at least 1 dose of study medication. |
| Arm/Group Title | Placebo | Rotigotine |
|---|---|---|
| Arm/Group Description | Subjects randomized to placebo received matching placebo patches. | 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. |
| Period Title: Overall Study | ||
| STARTED | 172 | 174 |
| COMPLETED | 151 | 160 |
| NOT COMPLETED | 21 | 14 |
Baseline Characteristics
| Arm/Group Title | Placebo | Rotigotine | Total Title |
|---|---|---|---|
| Arm/Group Description | Subjects randomized to placebo received matching placebo patches. | 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. | |
| Overall Participants | 172 | 174 | 346 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
96
55.8%
|
111
63.8%
|
207
59.8%
|
| >=65 years |
76
44.2%
|
63
36.2%
|
139
40.2%
|
| Age (years) [Mean (Standard Deviation) ] | |||
| mean (standard deviation) |
62.8
(9.1)
|
61.7
(8.8)
|
62.2
(8.9)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
62
36%
|
81
46.6%
|
143
41.3%
|
| Male |
110
64%
|
93
53.4%
|
203
58.7%
|
| Weight (kg) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [kg] |
61.83
(10.18)
|
60.38
(10.15)
|
61.10
(10.18)
|
Outcome Measures
| Title | Absolute Change in Absolute Time Spent 'Off' From Baseline to the End of Double-blind Maintenance Period |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Full Analysis Set (Placebo Treated Subjects) | Full Analysis Set (Rotigotine Treated Subjects) |
|---|---|---|
| Arm/Group Description | Subjects randomized to placebo received matching placebo patches. | 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. |
| Measure Participants | 168 | 170 |
| Mean (Standard Deviation) [hours] |
-1.13
(3.20)
|
-2.36
(2.83)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Full Analysis Set (Placebo Treated Subjects), Full Analysis Set (Rotigotine Treated Subjects) |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.0002 |
| Comments | Primary efficacy analyses was made with confirmatory 2-sided test with significance level 0.05. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Square Mean |
| Estimated Value | -1.20 | |
| Confidence Interval |
(2-Sided) 95% -1.83 to -0.57 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Responders From Baseline to the End of the Doubleblind Maintenance Period |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Full Analysis Set (Placebo Treated Subjects) | Full Analysis Set (Rotigotine Treated Subjects) |
|---|---|---|
| Arm/Group Description | Subjects randomized to placebo received matching placebo patches. | Subjects received rotigotine patches in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h or matching placebo was achieved. Each dose level was maintained for 1 week. |
| Measure Participants | 168 | 170 |
| Number [percentage of participants] |
36.9
21.5%
|
48.8
28%
|
| Title | Percent Change in Absolute Time Spent "Off" From Baseline to the End of Double-blind Maintenance Period |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Full Analysis Set (Placebo Treated Subjects) | Full Analysis Set (Rotigotine Treated Subjects) |
|---|---|---|
| Arm/Group Description | Subjects randomized to placebo received matching placebo patches. | Subjects received rotigotine patches in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h or matching placebo was achieved. Each dose level was maintained for 1 week. |
| Measure Participants | 168 | 170 |
| Mean (Standard Deviation) [percent change] |
-15.0
(56.56)
|
-36.03
(43.03)
|
| Title | Percent Change in Relative Time Spent "Off" From Baseline to the End of Double-blind Maintenance Period |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Full Analysis Set (Placebo Treated Subjects) | Full Analysis Set (Rotigotine Treated Subjects) |
|---|---|---|
| Arm/Group Description | Subjects randomized to placebo received matching placebo patches. | Subjects received rotigotine patches in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h or matching placebo was achieved. Each dose level was maintained for 1 week. |
| Measure Participants | 168 | 170 |
| Mean (Standard Deviation) [percent change] |
-14.86
(53.26)
|
-34.97
(43.87)
|
| Title | Change in Absolute Time Spent "on" From Baseline to the End of Double-blind Maintenance Period |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Full Analysis Set (Placebo Treated Subjects) | Full Analysis Set (Rotigotine Treated Subjects) |
|---|---|---|
| Arm/Group Description | Subjects randomized to placebo received matching placebo patches. | Subjects received rotigotine patches in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h or matching placebo was achieved. Each dose level was maintained for 1 week. |
| Measure Participants | 168 | 170 |
| Mean (Standard Deviation) [hours] |
0.94
(3.08)
|
2.05
(2.98)
|
| Title | Change in Relative Time Spent "on" From Baseline to the End of Double-blind Maintenance Period |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Full Analysis Set (Placebo Treated Subjects) | Full Analysis Set (Rotigotine Treated Subjects) |
|---|---|---|
| Arm/Group Description | Subjects randomized to placebo received matching placebo patches. | Subjects received rotigotine patches in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h or matching placebo was achieved. Each dose level was maintained for 1 week. |
| Measure Participants | 168 | 170 |
| Mean (Standard Deviation) [hours] |
6.78
(19.61)
|
14.49
(18.70)
|
| Title | Percent Change in Absolute Time Spent "on" From Baseline to the End of Double-blind Maintenance Period |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Full Analysis Set (Placebo Treated Subjects) | Full Analysis Set (Rotigotine Treated Subjects) |
|---|---|---|
| Arm/Group Description | Subjects randomized to placebo received matching placebo patches. | Subjects received rotigotine patches in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h or matching placebo was achieved. Each dose level was maintained for 1 week. |
| Measure Participants | 168 | 170 |
| Mean (Standard Deviation) [percent change] |
13.53
(42.74)
|
368.55
(4446.55)
|
| Title | Percent Change in Relative Time Spent "on" From Baseline to the End of Double-blind Maintenance Period |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Full Analysis Set (Placebo Treated Subjects) | Full Analysis Set (Rotigotine Treated Subjects) |
|---|---|---|
| Arm/Group Description | Subjects randomized to placebo received matching placebo patches. | Subjects received rotigotine patches in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h or matching placebo was achieved. Each dose level was maintained for 1 week. |
| Measure Participants | 168 | 170 |
| Mean (Standard Deviation) [percent change] |
14.99
(42.60)
|
616.80
(7667.58)
|
| Title | Change in the Number of "Off" Periods From Baseline to the End of Double-blind Maintenance Period |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Full Analysis Set (Placebo Treated Subjects) | Full Analysis Set (Rotigotine Treated Subjects) |
|---|---|---|
| Arm/Group Description | Subjects randomized to placebo received matching placebo patches. | Subjects received rotigotine patches in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h or matching placebo was achieved. Each dose level was maintained for 1 week. |
| Measure Participants | 168 | 170 |
| Mean (Standard Deviation) [Number of 'off' Periods] |
-0.61
(1.59)
|
-0.89
(1.32)
|
| Title | Change in Status of the Subject (on) After Wake-up With Troublesome Dyskinesia From Baseline to the End of Double-blind Maintenance Period |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Full Analysis Set (Placebo Treated Subjects) | Full Analysis Set (Rotigotine Treated Subjects) |
|---|---|---|
| Arm/Group Description | Subjects randomized to placebo received matching placebo patches. | Subjects received rotigotine patches in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h or matching placebo was achieved. Each dose level was maintained for 1 week. |
| Measure Participants | 168 | 170 |
| Mean (Standard Deviation) [percentage of days] |
2.42
(21.70)
|
1.24
(16.90)
|
| Title | Change in Status of the Subject (on) After Wake-up Without Troublesome Dyskinesia From Baseline to the End of Double-blind Maintenance Period |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Full Analysis Set (Placebo Treated Subjects) | Full Analysis Set (Rotigotine Treated Subjects) |
|---|---|---|
| Arm/Group Description | Subjects randomized to placebo received matching placebo patches. | Subjects received rotigotine patches in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h or matching placebo was achieved. Each dose level was maintained for 1 week. |
| Measure Participants | 168 | 170 |
| Mean (Standard Deviation) [percentage of days] |
7.92
(43.29)
|
22.55
(45.41)
|
| Title | Change in Status of the Subject (Off) After Wake-up From Baseline to the End of Double-blind Maintenance Period |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Full Analysis Set (Placebo Treated Subjects) | Full Analysis Set (Rotigotine Treated Subjects) |
|---|---|---|
| Arm/Group Description | Subjects randomized to placebo received matching placebo patches. | Subjects received rotigotine patches in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h or matching placebo was achieved. Each dose level was maintained for 1 week. |
| Measure Participants | 168 | 170 |
| Mean (Standard Deviation) [percentage of days] |
-10.34
(47.81)
|
-21.14
(48.49)
|
| Title | 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 |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Full Analysis Set (Placebo Treated Subjects) | Full Analysis Set (Rotigotine Treated Subjects) |
|---|---|---|
| Arm/Group Description | Subjects randomized to placebo received matching placebo patches. | Subjects received rotigotine patches in escalating weekly doses (starting with daily doses of rotigotine 4 mg/ 24 h) until an optimal dose or maximal dose of rotigotine 16 mg/ 24 h or matching placebo was achieved. Each dose level was maintained for 1 week. |
| Measure Participants | 168 | 170 |
| Mean (Standard Deviation) [units on a scale] |
-3.6
(9.8)
|
-10.4
(10.4)
|
Adverse Events
| Time Frame | Treatment-emergent Adverse Events (TEAE) were collected during the study, which began in August 2012 and concluded in October 2014. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | TEAEs are comprised of the Safety Population (SS), which consists of all randomized subjects who received at least 1 dose of study medication. | |||
| Arm/Group Title | Placebo | Rotigotine | ||
| Arm/Group Description | Placebo, daily doses, placebo Group Subjects randomized to placebo will receive matching placebo patches. | Rotigotine, daily doses, treatment Group Subjects will receive rotigotine or placebo patches 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 or matching placebo is achieved. A combination of patches (rotigotine or matching placebo) will be applied for subjects who require a dose > 8 mg/ 24 h. Each dose level is maintained for 1 week. | ||
All Cause Mortality |
||||
| Placebo | Rotigotine | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Placebo | Rotigotine | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/172 (3.5%) | 6/174 (3.4%) | ||
| Cardiac disorders | ||||
| Mitral valve prolapse | 1/172 (0.6%) | 1 | 0/174 (0%) | 0 |
| Atrial fibrillation | 1/172 (0.6%) | 1 | 0/174 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Intestinal obstruction | 1/172 (0.6%) | 1 | 0/174 (0%) | 0 |
| Inguinal hernia | 0/172 (0%) | 0 | 1/174 (0.6%) | 1 |
| Gastrointestinal haemorrhage | 0/172 (0%) | 0 | 1/174 (0.6%) | 1 |
| Infections and infestations | ||||
| Skin infection | 0/172 (0%) | 0 | 1/174 (0.6%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Spinal compression fracture | 0/172 (0%) | 0 | 1/174 (0.6%) | 1 |
| Nervous system disorders | ||||
| Syncope | 0/172 (0%) | 0 | 2/174 (1.1%) | 2 |
| Parkinson's disease | 1/172 (0.6%) | 1 | 0/174 (0%) | 0 |
| Renal and urinary disorders | ||||
| Urinary retention | 1/172 (0.6%) | 1 | 0/174 (0%) | 0 |
| Vascular disorders | ||||
| Vasculitis | 1/172 (0.6%) | 1 | 0/174 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Placebo | Rotigotine | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 24/172 (14%) | 54/174 (31%) | ||
| Gastrointestinal disorders | ||||
| Nausea | 2/172 (1.2%) | 2 | 16/174 (9.2%) | 23 |
| Nervous system disorders | ||||
| Dyskinesia | 7/172 (4.1%) | 7 | 11/174 (6.3%) | 13 |
| Dizziness | 7/172 (4.1%) | 8 | 19/174 (10.9%) | 21 |
| Skin and subcutaneous tissue disorders | ||||
| Pruritus | 10/172 (5.8%) | 11 | 14/174 (8%) | 15 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
UCB has > 60 but <= 180 days to review results communications prior to public release and may delete information that is confidential and compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that the results shall be published regardless of outcome.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | UCB |
| Phone | +1877 822 ext 9493 |
- SP1037