Parkinson Disease
Conditions
Keywords
Parkinson disease, Ropinirole
Brief summary
1. In order to compare the benefit, side effects, and patient preference of Ropinirole prolonged release when used in once-daily or twice-daily dosing 2. In order to estimate the conversion rate of dopamine agonists into Ropinirole prolonged release
Detailed description
1. Study subjects : Parkinson disease who are on Ropinirole immediate release or Pramipexole immediate release and are considering to change into Ropinirole prolonged release 2. Cross over study design: * Group 1: once daily dose for 2 month then into twice daily in divided dose for 2 months * Group 2: twice daily in divided dose for 2 months then into once daily dose for 2 months 3. Dose adjustment may be done in the first 4 weeks. 4. Compare the benefit,side effects, and patient preference between the once daily vs twice daily dosing.
Interventions
Change Ropinirole immediate release or Pramipexole immediate release to Ropinirole prolonged release (PR) once-daily or twice-daily
Sponsors
Seoul National University Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Age: 30-80 2. Parkinson disease 3. On dopamine agonists (Ropinirole IR or Pramipexole IR) and are considering to change into Ropinirole PR 4. On stable antiparkinsonian medication for at least 4 weeks 5. Who signed consent to the study
Exclusion criteria
1. Who are on less than 2 mg of Ropinirole IR or 0.375 mg of Pramipexole IR 2. Who have dementia, psychosis, major depression and other serious neurological or medical problems 3. Who are allergic to the similar medications 4. Who has history of heavy metal poisoning 5. Who were on othe clinical trials of other medications within the last 4 weeks 6. Whoa re pregnant or lactating 7. Who are considered not eligible by the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patient Preference | After 16 weeks or at last visit for early completion | Patient preference between once-daily and twice-daily regimen |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hoehn and Yahr Stage | 8 weeks for each arm or at last visit | Hoehn and Yahr(HY) stage for parkinsonism after 8 weeks in each arm or at last visit for early completion Range: 0\ 5 Higher values represent more severe parkinsonism |
| Overall Quality of Sleep | 8 weeks for each arm or at last visit | Sleep questionnaire 1 for Overall quality of sleep Visual analogue scale: 0\ 10 Higher values represent worse overall sleep quality. |
| Nocturnal Off-symptoms | 8 weeks for each arm or at last visit | Sleep questionnaire 2 for Nocturnal off-symptoms Visual analogue scale: 0\ 10 Higher values represent worse nocturnal off-symptoms. |
| Early Morning Off Symptoms | 8 weeks for each arm or at last visit | Sleep questionnaire 3 for early morning off symptoms Visual analogue scale: 0\ 10 Higher values represent worse early morning off symptoms. |
| Epworth Sleep Scale | 8 weeks in each arm or at last visit for early completion | Epworth sleep scale after 8 weeks in each arm or at last visit for early completion. Range: 0\ 24 Higher values represent worse daytime-sleepiness. |
| Compliance | 8 weeks for each arm or at last visit | Compliances after 8 weeks in each arm or at last visit for early completion. Compliance was calcuated by the percentage of used medication. |
| Unified Parkinson's Disease Rating Scale, Part 3 | 8 weeks for each arm or at last visit | Unified Parkinson's disease rating scale (UPDRS) motor scale after 8 weeks in each arm or at last visit for early completion. UPDRS part 3 is motor scale for parkinson's disease. Range: 0\ 108 Higher values represent more severe motor symptoms of parkinsonism. |
| Patients Who Have Global Impression for Improvement | After 8 weeks in each arm or at last visit for early completion | Patients who have global impression for improvement for each dosing. |
| Patients Who Have Global Impression for Improvement to Duration of Motor Fluctuation | After 8 weeks in each arm or at last visit for early completion | Patients who have global impression for improvement to duration of motor fluctuation |
| Patients Who Have Global Impression for Improvement to Severity of Motor Fluctuation | After 8 weeks in each arm or at last visit for early completion | Patients who have global impression for improvement to severity of motor fluctuation compared |
| Patients Who Have Global Impression for Improvement to Duration of Dyskinesia | After 8 weeks in each arm or at last visit for early completion | Patients who have global impression for improvement to duration of dyskinesia compared |
| Patients Who Have Global Impression for Improvement to Severity of Dyskinesia | After 8 weeks in each arm or at last visit for early completion | Patients who have Global Impression for Improvement to Severity of Dyskinesia compared |
| Adverse Events | After 8 weeks in each arm or at last visit for early completion | Patients who have adverse events |
Countries
South Korea
Participant flow
Recruitment details
The first subject was enrolled in September 2009 and the last subject completed the study in December 2010.
Pre-assignment details
A total of 82 patients with PD were enrolled in this study at two centers in Seoul, Korea.
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Includes groups randomized to receive once daily first and twice daily first. | 82 |
| Total | 82 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Lack of Efficacy | 1 | 2 |
| First Intervention | Out of indication | 1 | 0 |
| First Intervention | Poor compliance | 8 | 4 |
| First Intervention | Protocol Violation | 0 | 1 |
| First Intervention | Withdrawal by Subject | 0 | 1 |
| Second Intervention | Lost to Follow-up | 1 | 0 |
| Second Intervention | Poor compliance | 1 | 0 |
| Second Intervention | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 31 Participants |
| Age, Categorical Between 18 and 65 years | 51 Participants |
| Age Continuous | 61.8 years STANDARD_DEVIATION 9 |
| Region of Enrollment Korea, Republic of | 82 participants |
| Sex: Female, Male Female | 50 Participants |
| Sex: Female, Male Male | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 33 / 61 | 28 / 61 |
| serious Total, serious adverse events | 0 / 61 | 0 / 61 |
Outcome results
Primary
Patient Preference
Patient preference between once-daily and twice-daily regimen
Time frame: After 16 weeks or at last visit for early completion
Population: Primary outcome measure was the preference of the subjects between once-daily versus twice-daily of RPR at the completion or at early completion after crossover.~61 of participants completing period with study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Once-daily | Patient Preference | 17 participants |
| Twice-daily | Patient Preference | 31 participants |
| No Preference | Patient Preference | 13 participants |
Secondary
Adverse Events
Patients who have adverse events
Time frame: After 8 weeks in each arm or at last visit for early completion
Population: Total number of patients are 61 (Group 1 + Group 2), because of Crossover design. QD or BID arm means clinical variables measured in once-daily or twice-daily regimen, respectively.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Once-daily | Adverse Events | 33 participants |
| Twice-daily | Adverse Events | 28 participants |
Secondary
Compliance
Compliances after 8 weeks in each arm or at last visit for early completion. Compliance was calcuated by the percentage of used medication.
Time frame: 8 weeks for each arm or at last visit
Population: Total number of patients are 61 (Group 1 + Group 2), because of Crossover design. QD or BID arm means clinical variables measured in once-daily or twice-daily regimen, respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Once-daily | Compliance | 98.4 percentage of used medication | Standard Deviation 3.9 |
| Twice-daily | Compliance | 97.6 percentage of used medication | Standard Deviation 3.7 |
p-value: <0.05Sign test
Secondary
Early Morning Off Symptoms
Sleep questionnaire 3 for early morning off symptoms Visual analogue scale: 0\ 10 Higher values represent worse early morning off symptoms.
Time frame: 8 weeks for each arm or at last visit
Population: Total number of patients are 61 (Group 1 + Group 2), because of Crossover design. QD or BID arm means clinical variables measured in once-daily or twice-daily regimen, respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Once-daily | Early Morning Off Symptoms | 2.5 units on a scale | Standard Deviation 3.3 |
| Twice-daily | Early Morning Off Symptoms | 2.9 units on a scale | Standard Deviation 3.2 |
Comparison: The Early morning off symptoms was compared between the Once-daily of Ropinirole PR arm and the Twice-daily of Ropinirole PR using the Wilcoxon signed rank test.p-value: <0.05Sign test
Secondary
Epworth Sleep Scale
Epworth sleep scale after 8 weeks in each arm or at last visit for early completion. Range: 0\ 24 Higher values represent worse daytime-sleepiness.
Time frame: 8 weeks in each arm or at last visit for early completion
Population: Total number of patients are 61 (Group 1 + Group 2), because of Crossover design. QD or BID arm means clinical variables measured in once-daily or twice-daily regimen, respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Once-daily | Epworth Sleep Scale | 6.3 units on a scale | Standard Deviation 5.2 |
| Twice-daily | Epworth Sleep Scale | 6.4 units on a scale | Standard Deviation 4.8 |
Comparison: The Epworth sleep scale was compared between the Once-daily of Ropinirole PR arm and the Twice-daily of Ropinirole PR using the Wilcoxon signed rank test.p-value: <0.05Sign test
Secondary
Hoehn and Yahr Stage
Hoehn and Yahr(HY) stage for parkinsonism after 8 weeks in each arm or at last visit for early completion Range: 0\ 5 Higher values represent more severe parkinsonism
Time frame: 8 weeks for each arm or at last visit
Population: Total number of patients are 61 (Group 1 + Group 2), because of Crossover design. Once-daily or twice-daily arm means clinical variables measured in once-daily or twice-daily regimen, respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Once-daily | Hoehn and Yahr Stage | 2.1 Scores on a scale | Standard Deviation 0.5 |
| Twice-daily | Hoehn and Yahr Stage | 2.1 Scores on a scale | Standard Deviation 0.6 |
Comparison: The Hoehn and Yahr stage was compared between the Once-daily of Ropinirole PR arm and the Twice-daily of Ropinirole PR using the Wilcoxon signed rank test.p-value: <0.05Sign test
Secondary
Nocturnal Off-symptoms
Sleep questionnaire 2 for Nocturnal off-symptoms Visual analogue scale: 0\ 10 Higher values represent worse nocturnal off-symptoms.
Time frame: 8 weeks for each arm or at last visit
Population: Total number of patients are 61 (Group 1 + Group 2), because of Crossover design. QD or BID arm means clinical variables measured in once-daily or twice-daily regimen, respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Once-daily | Nocturnal Off-symptoms | 2.9 units on a scale | Standard Deviation 3.2 |
| Twice-daily | Nocturnal Off-symptoms | 3.1 units on a scale | Standard Deviation 3.2 |
Comparison: The Nocturnal off-symptoms was compared between the Once-daily of Ropinirole PR arm and the Twice-daily of Ropinirole PR using the Wilcoxon signed rank test.p-value: <0.05Sign test
Secondary
Overall Quality of Sleep
Sleep questionnaire 1 for Overall quality of sleep Visual analogue scale: 0\ 10 Higher values represent worse overall sleep quality.
Time frame: 8 weeks for each arm or at last visit
Population: Total number of patients are 61 (Group 1 + Group 2), because of Crossover design. QD or BID arm means clinical variables measured in once-daily or twice-daily regimen, respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Once-daily | Overall Quality of Sleep | 2.9 units on a scale | Standard Deviation 2.6 |
| Twice-daily | Overall Quality of Sleep | 3.2 units on a scale | Standard Deviation 2.5 |
Comparison: The Overall quality of sleep was compared between the Once-daily of Ropinirole PR arm and the Twice-daily of Ropinirole PR using the Wilcoxon signed rank test.p-value: <0.05Sign test
Secondary
Patients Who Have Global Impression for Improvement
Patients who have global impression for improvement for each dosing.
Time frame: After 8 weeks in each arm or at last visit for early completion
Population: The number of patient who completed the study and answered the questionnaire for global impression.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Once-daily | Patients Who Have Global Impression for Improvement | 32 participants |
| Twice-daily | Patients Who Have Global Impression for Improvement | 42 participants |
Secondary
Patients Who Have Global Impression for Improvement to Duration of Dyskinesia
Patients who have global impression for improvement to duration of dyskinesia compared
Time frame: After 8 weeks in each arm or at last visit for early completion
Population: The number of patient who completed the study and answered the questionnaire for global impression to dyskinesia duration.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Once-daily | Patients Who Have Global Impression for Improvement to Duration of Dyskinesia | 13 participants |
| Twice-daily | Patients Who Have Global Impression for Improvement to Duration of Dyskinesia | 16 participants |
Secondary
Patients Who Have Global Impression for Improvement to Duration of Motor Fluctuation
Patients who have global impression for improvement to duration of motor fluctuation
Time frame: After 8 weeks in each arm or at last visit for early completion
Population: The number of patient who completed the study and answered the questionnaire for global impression to motor fluctuation duration.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Once-daily | Patients Who Have Global Impression for Improvement to Duration of Motor Fluctuation | 27 participants |
| Twice-daily | Patients Who Have Global Impression for Improvement to Duration of Motor Fluctuation | 38 participants |
Secondary
Patients Who Have Global Impression for Improvement to Severity of Dyskinesia
Patients who have Global Impression for Improvement to Severity of Dyskinesia compared
Time frame: After 8 weeks in each arm or at last visit for early completion
Population: The number of patient who completed the study and answered the questionnaire for global impression to dyskinesia severity.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Once-daily | Patients Who Have Global Impression for Improvement to Severity of Dyskinesia | 16 participants |
| Twice-daily | Patients Who Have Global Impression for Improvement to Severity of Dyskinesia | 15 participants |
Secondary
Patients Who Have Global Impression for Improvement to Severity of Motor Fluctuation
Patients who have global impression for improvement to severity of motor fluctuation compared
Time frame: After 8 weeks in each arm or at last visit for early completion
Population: The number of patient who completed the study and answered the questionnaire for global impression to motor fluctuation severity.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Once-daily | Patients Who Have Global Impression for Improvement to Severity of Motor Fluctuation | 28 participants |
| Twice-daily | Patients Who Have Global Impression for Improvement to Severity of Motor Fluctuation | 34 participants |
Secondary
Unified Parkinson's Disease Rating Scale, Part 3
Unified Parkinson's disease rating scale (UPDRS) motor scale after 8 weeks in each arm or at last visit for early completion. UPDRS part 3 is motor scale for parkinson's disease. Range: 0\ 108 Higher values represent more severe motor symptoms of parkinsonism.
Time frame: 8 weeks for each arm or at last visit
Population: Total number of patients are 61 (Group 1 + Group 2), because of Crossover design. Once-daily or Twice-daily arm means clinical variables measured in once-daily or twice-daily regimen, respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Once-daily | Unified Parkinson's Disease Rating Scale, Part 3 | 17.5 units on a scale | Standard Deviation 8.2 |
| Twice-daily | Unified Parkinson's Disease Rating Scale, Part 3 | 17.1 units on a scale | Standard Deviation 8.9 |
Comparison: The UPDRS-part3 was compared between the Once-daily of Ropinirole PR arm and the Twice-daily of Ropinirole PR using the Wilcoxon signed rank test.p-value: <0.05Sign test