Advanced Idiopathic Parkinson's Disease
Conditions
Keywords
Rotigotine, Neupro, Polysomnography, Sleep efficiency, Advanced Idiopathic Parkinson's Disease, Sleep Disorder
Brief summary
This is a phase 4 study to evaluate with Polysomnography (PSG) and subjective measures the effect of Rotigotine on sleep efficiency, maintenance, insomnia, nocturnal akinesia and night-time movement in bed, in patients with advanced Parkinson's disease.
Interventions
OTHERPlacebo
Placebo patches size equivalent to 4, 6 & 8 mg/24 h. Daily application of Placebo patches starting at 4 mg/24 h. Dose will be up-titrated weekly by increments of 2 mg/24 h until optimal or maximal dose is reached. Maximal dose is 16 mg/24 h. Optimal or maximal dose will be maintained for 4 Weeks followed by a de-escalation by 2 mg/24 h every other day.
OTHERRotigotine
Rotigotine patches of 4,6 & 8 mg/24 h. Daily application of Rotigotine patches starting at 4 mg/24 h. Dose will be up-titrated weekly by increments of 2 mg/24 h until optimal or maximal dose is reached. Maximal dose is 16 mg/24 h. Optimal or maximal dose will be maintained for 4 weeks followed by a de-escalation by 2 mg/24 h every other day.
Sponsors
UCB Pharma SA
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
* Advanced Parkinson's disease (ie, takes Levodopa (L-DOPA)) * Hoehn and Yahr stage score of 2 to 4 * Subject has sleep-maintenance insomnia
Exclusion criteria
* Significant skin disease that would make transdermal drug use inappropriate * Subject received therapy with controlled-release Levodopa (L-DOPA), entacapone or Stalevo® within 28 days prior to the Baseline Visit or has received therapy with Tolcapone * Atypical Parkinsonian syndromes * Previous diagnosis of Narcolepsy, Sleep Apnoea Syndrome, significant Rapid Eye Movement (REM) Sleep Behavior Disorder (RBD), moderate to severe Restless Legs Syndrome (RLS) or Periodic Limb Movement Disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change From Baseline in Sleep Efficiency Index (SEI) to Week 4 of the Maintenance Period | From Baseline to Week 4 of the Maintenance Period (up to 11 weeks post-baseline) | The Sleep Efficiency Index in percent is the ratio of total sleep time (based on Polysomnography recordings) to time in bed (period between lights off and lights on). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Parkinson's Disease Sleep Scale Score Version 2 (PDSS2) to Week 4 of the Maintenance Period | From Baseline to Week 4 of the Maintenance Period (up to 11 weeks post-baseline) | The PDSS2 is a scale to assess sleep and nocturnal disability in Parkinson's Disease during the previous 7 days, and is designed for self-completion by the subject. The updated version (PDSS2) contains 15 questions to be answered using a 5-point Likert scale, where 0 = never, 1 = occasionally, 2 = sometimes, 3 = often, and 4 = very often. Thus, PDSS2 score ranges from 0-60, with higher scores indicating worse sleep and higher nocturnal disability. A negative value in Change from Baseline indicates improved sleep and less nocturnal disability. |
| Change From Baseline in the Epworth Sleepiness Score (ESS) to Day 1 of the Maintenance Period | From Baseline to Day 1 of the Maintenance Period (up to 7 weeks post-baseline) | The ESS measures the subject's general level of daytime sleepiness. The 8 items of this scale assess the probability of falling asleep in a variety of situations. Each item is scored by the subject using the following categories: 0 = would never doze, 1 = slight chance of dozing, 2 = moderate chance of dozing, and 4 = high chance of dozing. The ESS score ranges from 0 to 32, with higher values indicating a higher level of daytime sleepiness. A negative value in Change from Baseline indicates a decrease in daytime sleepiness. |
| Change From Baseline in the Epworth Sleepiness Score (ESS) to Week 4 of the Maintenance Period | From Baseline to Week 4 of the Maintenance Period (up to 11 weeks post-baseline) | The ESS measures the subject's general level of daytime sleepiness. The 8 items of this scale assess the probability of falling asleep in a variety of situations. Each item is scored by the subject using the following categories: 0 = would never doze, 1 = slight chance of dozing, 2 = moderate chance of dozing, and 4 = high chance of dozing. The ESS score ranges from 0 to 32, with higher values indicating a higher level of daytime sleepiness. A negative value in Change from Baseline indicates a decrease in daytime sleepiness. |
| Change From Baseline in the Sleep Period Time in Non-Rapid Eye Movement (Non-REM) Sleep to Week 4 of the Maintenance Period | From Baseline to Week 4 of the Maintenance Period (up to 11 weeks post-baseline) | Polysomnography (PSG) was performed for the 2 consecutive nights prior to Day 1 and the 2 consecutive nights prior Week 4 of the Maintenance Period. Readings from the first night of the PSG will not be used for analysis as this is considered an adaptation night. The subject was not allowed to sleep during the daytime on the day of a PSG reading. The PSG was recorded for a minimum of 6 h and a maximum of 8 h. The sleep period time in stage 3 non-REM was derived from the hypnogram, based on Electroencephalogram (EEG), Electro-myogram (EMG), Electro-oculogram (EOG) and Electrocardiogram (ECG). Change from Baseline is calculated by: (Stage 3 non-REM time (in minutes) at Baseline)- (Stage 3 non-REM time (in minutes) at Week 4 of the MP). |
| Change From Baseline in the Parkinson's Disease Sleep Scale Score Version 2 (PDSS2) to Day 1 of the Maintenance Period | From Baseline to Day 1 of the Maintenance Period (up to 7 weeks post-baseline) | The PDSS is a scale to assess sleep and nocturnal disability in Parkinson's Disease during the previous 7 days, and is designed for self-completion by the subject. The updated version (PDSS2) contains 15 questions to be answered using a 5-point Likert scale, where 0 = never, 1 = occasionally, 2 = sometimes, 3 = often, and 4 = very often. Thus, PDSS2 score ranges from 0-60, with higher scores indicating worse sleep and higher nocturnal disability. A negative value in Change from Baseline indicates improved sleep and less nocturnal disability. |
| Change From Baseline in the Nocturnal Akinesia, Dystonia and Cramps Score (NADCS) to Week 4 of the Maintenance Period | From Baseline to Week 4 of the Maintenance Period (up to 11 weeks post-baseline) | The NADCS assesses nocturnal akinesia, dystonia, and cramps using an ordinal severity scale. While a score of 0 = normal and 4 = maximal severity, subjects can also rate their symptoms with values of 0.5, 1.5, 2.5, and 3.5. The nocturnal akinesia score was used to evaluate motor performance while the dystonia and cramps score was used to evaluate pain. A negative value in Change from Baseline indicates an improvement. |
| Change From Baseline in the Total Wake Time After Sleep Onset (WASO) to Week 4 of the Maintenance Period | From Baseline to Week 4 of the Maintenance Period (up to 11 weeks post-baseline) | Polysomnography (PSG) was performed for the 2 consecutive nights prior to Day 1 and the 2 consecutive nights prior Week 4 of the Maintenance Period. Readings from the first night of the PSG will not be used for analysis as this is considered an adaptation night. The subject was not allowed to sleep during the daytime on the day of a PSG reading. The PSG was recorded for a minimum of 6 h and a maximum of 8 h. Sleep stages and time spent in each sleep stage were determined from EEG readings. WASO was calculated by: (Time in bed (Period between lights off and lights on))-(Sleep time). |
| Change From Baseline in the Total Number of Turnings in Bed to Week 4 of the Maintenance Period | From Baseline to Week 4 of the Maintenance Period (up to 11 weeks post-baseline) | Polysomnography (PSG) was performed for the 2 consecutive nights prior to Day 1 and the 2 consecutive nights prior Week 4 of the Maintenance Period. Readings from the first night of the PSG will not be used for analysis as this is considered an adaptation night. The subject was not allowed to sleep during the daytime on the day of a PSG reading. The PSG was recorded for a minimum of 6 h and a maximum of 8 h. The number of turnings in bed was determined via a postural sensor placed on the subject's chest. |
| Change From Baseline in the Nocturnal Akinesia, Dystonia, and Cramps Score (NADCS) to Day 1 of the Maintenance Period | From Baseline to Day 1 of the Maintenance Period (up to 7 weeks post-baseline) | The NADCS assesses nocturnal akinesia, dystonia, and cramps using an ordinal severity scale. While a score of 0 = normal and 4 = maximal severity, subjects can also rate their symptoms with values of 0.5, 1.5, 2.5, and 3.5. The nocturnal akinesia score was used to evaluate motor performance while the dystonia and cramps score was used to evaluate pain. A negative value in Change from Baseline indicates an improvement. |
Countries
United Kingdom
Participant flow
Recruitment details
The study started in March 2012 and was conducted in the United Kingdom. It was terminated due to recruitment issues in January 2013.
Pre-assignment details
1 subjects was randomized to Placebo and started and completed the study (from Screening (Week 0) to the Safety Follow-Up Visit (Week 18)).
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo Transdermal Patches
Placebo : Placebo patches size equivalent to 4, 6 & 8 mg/24 h. Daily application of Placebo patches starting at 4 mg/24 h. Dose will be up-titrated weekly by increments of 2 mg/24 h until optimal or maximal dose is reached. Maximal dose is 16 mg/24 h.
Optimal or maximal dose will be maintained for 4 Weeks followed by a de-escalation by 2 mg/24 h every other day. | 1 |
| Rotigotine Rotigotine Transdermal Patches
Rotigotine : Rotigotine patches of 4,6 & 8 mg/24 h. Daily application of Rotigotine patches starting at 4 mg/24 h. Dose will be up-titrated weekly by increments of 2 mg/24 h until optimal or maximal dose is reached. Maximal dose is 16 mg/24 h.
Optimal or maximal dose will be maintained for 4 weeks followed by a de-escalation by 2 mg/24 h every other day. | 0 |
| Total | 1 |
Baseline characteristics
| Characteristic | Total | Placebo |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants |
| Age, Continuous | 67 years | 67 years |
| Region of Enrollment United Kingdom | 1 participants | 1 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 1 | 0 / 0 |
| serious Total, serious adverse events | 0 / 1 | 0 / 0 |
Outcome results
Primary
Percentage Change From Baseline in Sleep Efficiency Index (SEI) to Week 4 of the Maintenance Period
The Sleep Efficiency Index in percent is the ratio of total sleep time (based on Polysomnography recordings) to time in bed (period between lights off and lights on).
Time frame: From Baseline to Week 4 of the Maintenance Period (up to 11 weeks post-baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Percentage Change From Baseline in Sleep Efficiency Index (SEI) to Week 4 of the Maintenance Period | 4.7 percentage change |
Secondary
Change From Baseline in the Epworth Sleepiness Score (ESS) to Day 1 of the Maintenance Period
The ESS measures the subject's general level of daytime sleepiness. The 8 items of this scale assess the probability of falling asleep in a variety of situations. Each item is scored by the subject using the following categories: 0 = would never doze, 1 = slight chance of dozing, 2 = moderate chance of dozing, and 4 = high chance of dozing. The ESS score ranges from 0 to 32, with higher values indicating a higher level of daytime sleepiness. A negative value in Change from Baseline indicates a decrease in daytime sleepiness.
Time frame: From Baseline to Day 1 of the Maintenance Period (up to 7 weeks post-baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Change From Baseline in the Epworth Sleepiness Score (ESS) to Day 1 of the Maintenance Period | -1 units on a scale |
Secondary
Change From Baseline in the Epworth Sleepiness Score (ESS) to Week 4 of the Maintenance Period
The ESS measures the subject's general level of daytime sleepiness. The 8 items of this scale assess the probability of falling asleep in a variety of situations. Each item is scored by the subject using the following categories: 0 = would never doze, 1 = slight chance of dozing, 2 = moderate chance of dozing, and 4 = high chance of dozing. The ESS score ranges from 0 to 32, with higher values indicating a higher level of daytime sleepiness. A negative value in Change from Baseline indicates a decrease in daytime sleepiness.
Time frame: From Baseline to Week 4 of the Maintenance Period (up to 11 weeks post-baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Change From Baseline in the Epworth Sleepiness Score (ESS) to Week 4 of the Maintenance Period | 0 units on a scale |
Secondary
Change From Baseline in the Nocturnal Akinesia, Dystonia, and Cramps Score (NADCS) to Day 1 of the Maintenance Period
The NADCS assesses nocturnal akinesia, dystonia, and cramps using an ordinal severity scale. While a score of 0 = normal and 4 = maximal severity, subjects can also rate their symptoms with values of 0.5, 1.5, 2.5, and 3.5. The nocturnal akinesia score was used to evaluate motor performance while the dystonia and cramps score was used to evaluate pain. A negative value in Change from Baseline indicates an improvement.
Time frame: From Baseline to Day 1 of the Maintenance Period (up to 7 weeks post-baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Change From Baseline in the Nocturnal Akinesia, Dystonia, and Cramps Score (NADCS) to Day 1 of the Maintenance Period | -0.5 units on a scale |
Secondary
Change From Baseline in the Nocturnal Akinesia, Dystonia and Cramps Score (NADCS) to Week 4 of the Maintenance Period
The NADCS assesses nocturnal akinesia, dystonia, and cramps using an ordinal severity scale. While a score of 0 = normal and 4 = maximal severity, subjects can also rate their symptoms with values of 0.5, 1.5, 2.5, and 3.5. The nocturnal akinesia score was used to evaluate motor performance while the dystonia and cramps score was used to evaluate pain. A negative value in Change from Baseline indicates an improvement.
Time frame: From Baseline to Week 4 of the Maintenance Period (up to 11 weeks post-baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Change From Baseline in the Nocturnal Akinesia, Dystonia and Cramps Score (NADCS) to Week 4 of the Maintenance Period | -0.5 units on a scale |
Secondary
Change From Baseline in the Parkinson's Disease Sleep Scale Score Version 2 (PDSS2) to Day 1 of the Maintenance Period
The PDSS is a scale to assess sleep and nocturnal disability in Parkinson's Disease during the previous 7 days, and is designed for self-completion by the subject. The updated version (PDSS2) contains 15 questions to be answered using a 5-point Likert scale, where 0 = never, 1 = occasionally, 2 = sometimes, 3 = often, and 4 = very often. Thus, PDSS2 score ranges from 0-60, with higher scores indicating worse sleep and higher nocturnal disability. A negative value in Change from Baseline indicates improved sleep and less nocturnal disability.
Time frame: From Baseline to Day 1 of the Maintenance Period (up to 7 weeks post-baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Change From Baseline in the Parkinson's Disease Sleep Scale Score Version 2 (PDSS2) to Day 1 of the Maintenance Period | 3 units on a scale |
Secondary
Change From Baseline in the Parkinson's Disease Sleep Scale Score Version 2 (PDSS2) to Week 4 of the Maintenance Period
The PDSS2 is a scale to assess sleep and nocturnal disability in Parkinson's Disease during the previous 7 days, and is designed for self-completion by the subject. The updated version (PDSS2) contains 15 questions to be answered using a 5-point Likert scale, where 0 = never, 1 = occasionally, 2 = sometimes, 3 = often, and 4 = very often. Thus, PDSS2 score ranges from 0-60, with higher scores indicating worse sleep and higher nocturnal disability. A negative value in Change from Baseline indicates improved sleep and less nocturnal disability.
Time frame: From Baseline to Week 4 of the Maintenance Period (up to 11 weeks post-baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Change From Baseline in the Parkinson's Disease Sleep Scale Score Version 2 (PDSS2) to Week 4 of the Maintenance Period | 6 units on a scale |
Secondary
Change From Baseline in the Sleep Period Time in Non-Rapid Eye Movement (Non-REM) Sleep to Week 4 of the Maintenance Period
Polysomnography (PSG) was performed for the 2 consecutive nights prior to Day 1 and the 2 consecutive nights prior Week 4 of the Maintenance Period. Readings from the first night of the PSG will not be used for analysis as this is considered an adaptation night. The subject was not allowed to sleep during the daytime on the day of a PSG reading. The PSG was recorded for a minimum of 6 h and a maximum of 8 h. The sleep period time in stage 3 non-REM was derived from the hypnogram, based on Electroencephalogram (EEG), Electro-myogram (EMG), Electro-oculogram (EOG) and Electrocardiogram (ECG). Change from Baseline is calculated by: (Stage 3 non-REM time (in minutes) at Baseline)- (Stage 3 non-REM time (in minutes) at Week 4 of the MP).
Time frame: From Baseline to Week 4 of the Maintenance Period (up to 11 weeks post-baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Change From Baseline in the Sleep Period Time in Non-Rapid Eye Movement (Non-REM) Sleep to Week 4 of the Maintenance Period | 22 minutes |
Secondary
Change From Baseline in the Total Number of Turnings in Bed to Week 4 of the Maintenance Period
Polysomnography (PSG) was performed for the 2 consecutive nights prior to Day 1 and the 2 consecutive nights prior Week 4 of the Maintenance Period. Readings from the first night of the PSG will not be used for analysis as this is considered an adaptation night. The subject was not allowed to sleep during the daytime on the day of a PSG reading. The PSG was recorded for a minimum of 6 h and a maximum of 8 h. The number of turnings in bed was determined via a postural sensor placed on the subject's chest.
Time frame: From Baseline to Week 4 of the Maintenance Period (up to 11 weeks post-baseline)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Change From Baseline in the Total Number of Turnings in Bed to Week 4 of the Maintenance Period | 0 Number of turnings in bed |
Secondary
Change From Baseline in the Total Wake Time After Sleep Onset (WASO) to Week 4 of the Maintenance Period
Polysomnography (PSG) was performed for the 2 consecutive nights prior to Day 1 and the 2 consecutive nights prior Week 4 of the Maintenance Period. Readings from the first night of the PSG will not be used for analysis as this is considered an adaptation night. The subject was not allowed to sleep during the daytime on the day of a PSG reading. The PSG was recorded for a minimum of 6 h and a maximum of 8 h. Sleep stages and time spent in each sleep stage were determined from EEG readings. WASO was calculated by: (Time in bed (Period between lights off and lights on))-(Sleep time).
Time frame: From Baseline to Week 4 of the Maintenance Period (up to 11 weeks post-baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Change From Baseline in the Total Wake Time After Sleep Onset (WASO) to Week 4 of the Maintenance Period | 20 minutes |