Parkinson's Disease
Conditions
Keywords
rotigotine, Neupro®, Parkinson's Disease
Brief summary
The objective of this trial is to assess the effects of transdermal rotigotine on the control of early morning motor function and sleep disorders compared to placebo in subjects with idiopathic Parkinsons´s disease. In addition, effects of rotigotine on specific nocturnal and non-motor symptoms of Parkinson´s disease will be evaluated.
Detailed description
The objective of this trial is to assess the effects of rotigotine on the control of early morning motor function and sleep disorders compared to placebo in subjects with idiopathic Parkinsons´s disease. In addition, effects of rotigotine on specific nocturnal and non-motor symptoms of Parkinson´s disease will be evaluated. After a Screening Period of up to 28 days subjects will be hospitalized for two nights. After the second overnight stay, subjects will be randomly assigned either to rotigotine patch or placebo patch. Afterwards patients will be titrated to their optimal dose. After subjects have reached their optimal dose (or the highest dose) they will be maintained on this dose for a certain period. At the end of maintenance the subjects will be hospitalized for two nights. Afterwards the doses will be continuously decreased. Efficacy will be assessed by application of sleep quality scores, motor examination scores, and scores to evaluate non-motor symptoms of Parkinsons. Safety assessments include adverse events, 12-lead electrocardiograms, blood pressure and heart rate assessments, and laboratory checks.
Interventions
DRUGRotigotine
Rotigotine transdermal patches: 10cm2 (2mg/24h); 20cm2 (4mg/24h); 30cm2 (6mg/24h); 40cm2 (8mg/24h) Optimal dosing: The maximum Rotigotine dose allowed is 16mg/24h
OTHERPlacebo
Placebo transdermal patches
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
* Early and advanced Idiopathic Parkinson Disease with early morning motor impairment
Exclusion criteria
* Atypical Parkinsonian syndromes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Early Morning UPDRS Part III Score | From baseline to end of maintenance (after 4 weeks maintenance) | The Unified Parkinson´s Disease Rating Scale Part III score is an accepted and validated sumscore of 14 items for the assessment of motor function in Parkinson´s disease. Each of the 14 items in the UPDRS part III is measured on a scale of 0 to 4, where 0 is normal and 4 represents severe abnormalities. |
| Change in Parkinson's Disease Sleep Scale (PDSS) | From baseline to end of maintenance (after 4 weeks maintenance) | The Parkinson´s Disease Sleep Scale (PDSS) is a questionnaire with 15 questions to assess sleep and nocturnal disability in Parkinson´s disease. The item- scores can range between 0= never and 4= very often. The PDSS score is a sumscore of all 15 questions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Nocturnal Akinesia, Dystonia, and Cramps Score (NADCS) | From baseline to end of maintenance (after 4 weeks maintenance) | Subjects were asked to assess nocturnal akinesia, dystonia and cramps, using an ordinal severity scale. While a score of 0= normal and 4= maximal severity, subjects could also rate their symptoms with values of 0.5, 1.5, 2.5, 3.5. The nocturnal akinesia score was used to evaluate motor performance while the dystonia and cramps scores were used to evaluate sleep. |
| Change in Number of Nocturias | From baseline to end of maintenance (after 4 weeks maintenance) | Nocturia is the need to get up during the night and interrupt sleep in order to urinate. It is a typical nocturnal symptom of Parkinson´s disease. The change from baseline in number of nocturias was used to evaluate improvements in sleep disorders. |
Countries
Australia, Austria, Finland, Germany, Hungary, Italy, New Zealand, Poland, South Africa, Spain, United Kingdom, United States
Participant flow
Recruitment details
A total of 333 subjects were enrolled in this trial and comprised the Enrolled Set (ES). 287 subjects were randomized and all of them received at least 1 dose of trial medication, so they all belong to the Safety Set (SS). 267 subjects belong to the Full Analysis Set (FAS).
Pre-assignment details
Participant Flow shows all 287 subjects who has been enrolled and randomized. Baseline Characteristics are described for the Full Analysis Set (FAS).
Participants by arm
| Arm | Count |
|---|---|
| Rotigotine Rotigotine transdermal patch | 178 |
| Placebo Placebo transdermal patch | 89 |
| Total | 267 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 11 | 6 |
| Overall Study | Lack of Efficacy | 0 | 4 |
| Overall Study | Other | 2 | 0 |
| Overall Study | Withdrawal by Subject | 11 | 7 |
Baseline characteristics
| Characteristic | Rotigotine | Total | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 91 Participants | 140 Participants | 49 Participants |
| Age, Categorical Between 18 and 65 years | 87 Participants | 127 Participants | 40 Participants |
| Age, Continuous | 64.7 years STANDARD_DEVIATION 9.4 | 64.6 years STANDARD_DEVIATION 9.7 | 64.5 years STANDARD_DEVIATION 10.4 |
| Body Mass Index (BMI) | 26.676 kg/ m^2 STANDARD_DEVIATION 4.164 | 26.665 kg/ m^2 STANDARD_DEVIATION 4.295 | 26.645 kg/ m^2 STANDARD_DEVIATION 4.569 |
| Height | 169.04 cm STANDARD_DEVIATION 9.11 | 169.60 cm STANDARD_DEVIATION 9.18 | 170.73 cm STANDARD_DEVIATION 9.27 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 11 Participants | 19 Participants | 8 Participants |
| Race (NIH/OMB) White | 164 Participants | 243 Participants | 79 Participants |
| Sex: Female, Male Female | 61 Participants | 92 Participants | 31 Participants |
| Sex: Female, Male Male | 117 Participants | 175 Participants | 58 Participants |
| Weight | 76.6 kg STANDARD_DEVIATION 15.1 | 77.1 kg STANDARD_DEVIATION 15.5 | 78.0 kg STANDARD_DEVIATION 16.2 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 70 / 191 | 21 / 96 |
| serious Total, serious adverse events | 10 / 191 | 5 / 96 |
Outcome results
Primary
Change in Early Morning UPDRS Part III Score
The Unified Parkinson´s Disease Rating Scale Part III score is an accepted and validated sumscore of 14 items for the assessment of motor function in Parkinson´s disease. Each of the 14 items in the UPDRS part III is measured on a scale of 0 to 4, where 0 is normal and 4 represents severe abnormalities.
Time frame: From baseline to end of maintenance (after 4 weeks maintenance)
Population: Full Analysis Set (FAS) with Last Observation Carried Forward (LOCF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rotigotine | Change in Early Morning UPDRS Part III Score | -7.0 units on a scale | Standard Deviation 7.6 |
| Placebo | Change in Early Morning UPDRS Part III Score | -3.9 units on a scale | Standard Deviation 7.3 |
Comparison: Analyses of covariance were performed for the efficacy variables with treatment and (pooled) sites as factors, and baseline value as covariate. Least square means (LS means) for treatment effect were calculated and differences between rotigotine and placebo were presented with 95% confidence intervals (CIs) and p- values.p-value: 0.000295% CI: [-5.37, -1.73]ANCOVA
Primary
Change in Parkinson's Disease Sleep Scale (PDSS)
The Parkinson´s Disease Sleep Scale (PDSS) is a questionnaire with 15 questions to assess sleep and nocturnal disability in Parkinson´s disease. The item- scores can range between 0= never and 4= very often. The PDSS score is a sumscore of all 15 questions.
Time frame: From baseline to end of maintenance (after 4 weeks maintenance)
Population: Full Analysis Set (FAS) with Last Observation Carried Forward (LOCF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rotigotine | Change in Parkinson's Disease Sleep Scale (PDSS) | -5.9 units on a scale | Standard Deviation 7.6 |
| Placebo | Change in Parkinson's Disease Sleep Scale (PDSS) | -1.9 units on a scale | Standard Deviation 8.2 |
Comparison: Analyses of covariance were performed for the efficacy variables with treatment and (pooled) sites as factors, and baseline value as covariate. Least square means (LS means) for treatment effect were calculated and differences between rotigotine and placebo were presented with 95% confidence intervals (CIs) and p- values.p-value: <0.000195% CI: [-6.08, -2.45]ANCOVA
Secondary
Change in Nocturnal Akinesia, Dystonia, and Cramps Score (NADCS)
Subjects were asked to assess nocturnal akinesia, dystonia and cramps, using an ordinal severity scale. While a score of 0= normal and 4= maximal severity, subjects could also rate their symptoms with values of 0.5, 1.5, 2.5, 3.5. The nocturnal akinesia score was used to evaluate motor performance while the dystonia and cramps scores were used to evaluate sleep.
Time frame: From baseline to end of maintenance (after 4 weeks maintenance)
Population: Full Analysis Set (FAS).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rotigotine | Change in Nocturnal Akinesia, Dystonia, and Cramps Score (NADCS) | -1.3 units on a scale | Standard Deviation 1.8 |
| Placebo | Change in Nocturnal Akinesia, Dystonia, and Cramps Score (NADCS) | -0.9 units on a scale | Standard Deviation 2.1 |
Comparison: Analyses of covariance were performed for the efficacy variables with treatment and (pooled) sites as factors, and baseline value as covariate. Least square means (LS means) for treatment effect were calculated and differences between rotigotine and placebo were presented with 95% confidence intervals (CIs) and p- values.p-value: 0.030195% CI: [-0.79, -0.04]ANCOVA
Secondary
Change in Number of Nocturias
Nocturia is the need to get up during the night and interrupt sleep in order to urinate. It is a typical nocturnal symptom of Parkinson´s disease. The change from baseline in number of nocturias was used to evaluate improvements in sleep disorders.
Time frame: From baseline to end of maintenance (after 4 weeks maintenance)
Population: Full Analysis Set (FAS).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rotigotine | Change in Number of Nocturias | -0.3 nocturias | Standard Deviation 1.3 |
| Placebo | Change in Number of Nocturias | -0.2 nocturias | Standard Deviation 1.1 |
Comparison: Analyses of covariance were performed for the efficacy variables with treatment and (pooled) sites as factors, and baseline value as covariate. Least square means (LS means) for treatment effect were calculated and differences between rotigotine and placebo were presented with 95% confidence intervals (CIs) and p- values.p-value: 0.884295% CI: [-0.29, 0.25]ANCOVA