Parkinson Disease
Conditions
Brief summary
The objective of this trial is to evaluate non-inferiority of pramipexole Extended release to Immediate release at 18 weeks on the primary efficacy endpoint (Unified Parkinson's Disease Rating Scale II+III) in Chinese PD patients who can be concomitantly treated with Levodopa .
Interventions
DRUGpramipexole immediate release tablet
0.375mg-4.5mg(daily dose), three times a day
DRUGpramipexole extended release tablet
0.375mg-4.5mg, once a day
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female Chinese patient with idiopathic Parkinson's disease (PD) confirmed by at least two of the following signs: resting tremor, bradykinesia, rigidity. 2. Parkinson's disease diagnosed for at least 2 years. 3. Patients 30 years of age or older at the time of diagnosis. 4. Modified Hoehn and Yahr stage of 2 to 4 at on-time. 5. If a patient is treated with standard or controlled release Levodopa combined with a Dopa-Decarboxylase-inhibitor or with Levodopa combined with a Dopa-Decarboxylase-inhibitor/entacapone, the dosage should be optimised according to investigator's judgement, and stable for at least 4 weeks prior to baseline visit. 6. If a patient treated with Levodopa combined with a Dopa-Decarboxylase-inhibitor has motor fluctuations, he should not have more than 6 hours of off-time every day during waking hours (documented on a patient diary completed for 2 consecutive days before baseline visit). 7. Patient willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures (in particular, after training, the patient should be able to recognise the off-time and on-time periods during waking hours and to record them accurately in the patient diary). 8. Signed informed consent obtained before any study procedures are carried out (in accordance with International Conference on Harmonisation-Good Clinical Practice guidelines and local legislation).
Exclusion criteria
Medical exclusions: 1. Atypical parkinsonian syndromes due to drugs (e.g., metoclopramide, flunarizine), metabolic disorders (e.g., Wilson's disease), encephalitis or degenerative diseases (e.g., progressive supranuclear palsy). 2. Dementia, as defined by a Mini-Mental State Exam score \< 24 at screening visit \[R96-2656\]. 3. Any psychiatric disorder according to Diagnostic and Statistical Manual of Mental Disorders (4th edition)criteria that could prevent compliance or completion of the study and/or put the patient at risk if he/she takes part in the study. 4. History of psychosis, except history of drug induced hallucinations (provided the investigator considers that participation to the trial would not represent a significant risk for the patient). 5. History of deep brain stimulation 6. Clinically significant electrocardiogram abnormalities at screening visit, according to investigator's judgement. 7. Clinically significant hypotension (i.e. supine systolic blood pressure \< 90 mmHg) and/or symptomatic orthostatic hypotension (i.e. clinical symptoms of orthostatic hypotension associated with a decline \>=20 mmHg in systolic blood pressure and a decline \>= 10 mmHg in diastolic blood pressure, at one minute after standing compared with the previous supine systolic and diastolic blood pressure obtained after 5 minutes of quiet rest) at screening or baseline visit. 8. Malignant melanoma or history of previously treated malignant melanoma. 9. Any other clinically significant disease, whether treated or not, that could put the patient at risk or could prevent compliance or completion of the study. 10. Pregnancy (to be excluded by urine pregnancy test at screening visit) or breast-feeding. 11. Sexually active female of childbearing potential (less than 6 months post-menopausal and not surgically sterilised) not using a medically approved method of birth control (i.e. oral contraceptives, intrauterine device, or double-barrier) for at least one month prior to the screening visit and throughout the study period (up to the follow-up visit). 12. Serum levels of Aspartate Aminotransferase, Alanine Aminotransferase , alkaline phosphatases or total bilirubin \> 2 Upper Limit of Normal (on screening lab test). 13. Patients with a creatinine clearance \< 50 mL/min/1.73m2 (estimated by the local lab / the investigator using the Modification of Diet in Renal Disease (MDRD), and calculated on screening lab test)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Unified Parkinsons Disease Rating Scale (UPDRS) Parts II+III Score at Week 18 | Baseline and week 18 | UPDRS total score ranges from 0 (best) to 160 (worst) and was calculated as the sum of Part II (activities of daily living, ranges from 0 to 52) and Part III (motor examination, ranges from 0 to 108). Reduction over time represents an improvement. Means are adjusted for treatment, centre and baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Percentage Off-time During Waking Hours at Week 18 | Baseline and week 18 | Percentage off-time during waking hours based on patient diary data, percentage ranging from 0 (best case) to 100 (worst case). Off-time describes a period when the patient experiences increased parkinsonian symptoms (e.g. immobility or inability to move with ease). Reduction over time represents an improvement. Means are adjusted for treatment, centre and baseline. |
| Change From Baseline in Duration of Off-time During Waking Hours at Week 18 | Baseline and week 18 | Duration of off-time during waking hours based on patient diary data. Off-time describes a period when the patient experiences increased parkinsonian symptoms (e.g. immobility or inability to move with ease). Reduction over time represents an improvement. Means are adjusted for treatment, centre and baseline. |
| Responder in Percentage Off-time During Waking Hours at Week 18 | Baseline and week 18 | Percentage off-time based on patient diary data, percentage ranging from 0 (best case) to 100 (worst case). Off-time describes a period when the patient experiences increased parkinsonian symptoms (e.g. immobility or inability to move with ease). Reduction over time represents an improvement. Responders were defined as patients with at least a 20 percent improvement relative to baseline. |
| Change From Baseline in Percentage On-time Without Dyskinesia at Week 18 | Baseline and week 18 | Percentage on-time without Dyskinesia based on patient diary data, percentage ranging from 0 (worst case) to 100 (best case). On-time describes a period during which a patient was relatively free of Parkinsons symptoms (e.g. mobile or capable of moving with relative ease and independence). Increase in the percentage represents an improvement. Means are adjusted for treatment, centre and baseline. |
| Change From Baseline in Percentage On-time With Non-troublesome Dyskinesia at Week 18 | Baseline and week 18 | Percentage on-time with non-troublesome Dyskinesia based on patient diary data, percentage ranging from 0 (worst case) to 100 (best case). On-time describes a period during which a patient was relatively free of Parkinsons symptoms (e.g. mobile or capable of moving with relative ease and independence). Dyskinesia qualified as non-troublesome if it did not interfere with function or did not cause meaningful discomfort. Increase in the percentage represents an improvement. Means are adjusted for treatment, centre and baseline. |
| Change From Baseline in Percentage On-time Without or With Non-troublesome Dyskinesia at Week 18 | Baseline and week 18 | Percentage on-time without or with non-troublesome Dyskinesia based on patient diary data, percentage ranging from 0 (best case) to 100 (worst case). On-time describes a period during which a patient was relatively free of Parkinsons symptoms (e.g. mobile or capable of moving with relative ease and independence). Dyskinesia qualified as non-troublesome if it did not interfere with function or did not cause meaningful discomfort. Increase in the percentage represents an improvement. Means are adjusted for treatment, centre and baseline. |
| Change From Baseline in Percentage On-time With Troublesome Dyskinesia at Week 18 | Baseline and week 18 | Percentage on-time with troublesome Dyskinesia based on patient diary data, percentage ranging from 0 (best case) to 100 (worst case). On-time describes a period during which a patient was relatively free of Parkinsons symptoms (e.g. mobile or capable of moving with relative ease and independence). Dyskinesia qualified as troublesome if it interfered with function or caused meaningful discomfort. Decrease in the percentage represents an improvement. Means are adjusted for treatment, centre and baseline. |
| Change From Baseline in Duration of On-time Without Dyskinesia at Week 18 | Baseline and week 18 | Duration of on-time without Dyskinesia based on patient diary data. On-time describes a period during which a patient was relatively free of Parkinsons symptoms (e.g. mobile or capable of moving with relative ease and independence). Increase in the duration represents an improvement. Means are adjusted for treatment, centre and baseline. |
| Change From Baseline in Duration of On-time With Non-troublesome Dyskinesia at Week 18 | Baseline and week 18 | Duration on-time with non-troublesome Dyskinesia based on patient diary data, percentage ranging from 0 (worst case) to 100 (best case). On-time describes a period during which a patient was relatively free of Parkinsons symptoms (e.g. mobile or capable of moving with relative ease and independence). Dyskinesia qualified as non-troublesome if it did not interfere with function or did not cause meaningful discomfort. Increase in the duration represents an improvement. Means are adjusted for treatment, centre and baseline. |
| Change From Baseline in Duration of On-time With Troublesome Dyskinesia at Week 18 | Baseline and week 18 | Duration of on-time with troublesome Dyskinesia based on patient diary data, percentage ranging from 0 (best case) to 100 (worst case). On-time describes a period during which a patient was relatively free of Parkinsons symptoms (e.g. mobile or capable of moving with relative ease and independence). Dyskinesia qualified as troublesome if it interfered with function or caused meaningful discomfort. Decrease in the duration represents an improvement. Means are adjusted for treatment, centre and baseline. |
| Clinical Global Impression of Improvement (CGI-I) Responder at Week 18 | 18 weeks | CGI-I was used to assess the overall status of Parkinsons disease (PD) after interviewing the patient about the various aspects of the PD and after evaluating adverse events and concomitant treatments. Ranging from 1 point=very much improved to 7 points=very much worse. Responders were defined as patients having score 1 or 2 (at least much improved) when comparing the past week to the assessment at baseline. |
| Patient Global Impressions of Improvement (PGI-I) Responder at Week 18 | 18 weeks | The PGI-I scale is a patient-rated instrument which was used to measure the improvement of a patients PD symptoms throughout the study. Ranging from 1 point=very much better to 7 points=very much worse. Responders were defined as patients having score 1 or 2 (at least much better) when comparing the past week to the assessment at baseline. |
| Responder in UPDRS Parts II+III Score at Week 18 | Baseline and week 18 | Responders were defined as patients with at least a 20 percent improvement of UPDRS II+III score relative to baseline. UPDRS II+III ranges 0-160 scores from best to worst and was calculated as the sum of Part II (activities of daily living, ranges from 0 to 52) and Part III (motor examination, ranges from 0 to 108). |
| Change From Baseline in UPDRS II Score Separately at Week 18 | Baseline and week 18 | UPDRS Part II (activities of daily living) ranges from 0 to 52. Reduction over time represents an improvement. Means are adjusted for treatment, centre and baseline. |
| Change From Baseline in UPDRS III Score Separately at Week 18 | Baseline and week 18 | UPDRS Part III (motor examination) ranges from 0 to 108. Reduction over time represents an improvement. Means are adjusted for treatment, centre and baseline. |
| Levodopa (L-Dopa) Introduction During the Study | 18 weeks | Number of patients without concomitant L-Dopa treatment at baseline which required L-Dopa supplementation during the study. |
| Levodopa (L-Dopa) Dose Change During the Study | 18 weeks | Although the number of patients who began the study with concomitant L-dopa supplementation and required a change in dosage was not analysed for this study, the change from baseline in L-dopa dose is presented. |
| Change From Baseline in Duration of On-time Without or With Non-troublesome Dyskinesia at Week 18 | Baseline and week 18 | Duration of on-time without Dyskinesia or with non-troublesome Dyskinesia based on patient diary data, percentage ranging from 0 (worst case) to 100 (best case). On-time describes a period during which a patient was relatively free of Parkinsons symptoms (e.g. mobile or capable of moving with relative ease and independence). Dyskinesia qualified as non-troublesome if it did not interfere with function or did not cause meaningful discomfort. Increase in the duration represents an improvement. Means are adjusted for treatment, centre and baseline. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score at 18 Weeks | Baseline and week 18 | ESS is a patient-report scale with 8 items rating how likely one is to fall asleep during passive and inconsequential situations such as watching television, more active situations such as sitting and talking to someone, or consequential situations such as sitting in a car, while stopped for a few minutes in traffic. The likelihood of dozing off is rated from 0 points (no chance) to 3 points (high chance). The overall rating scale is scored from 0 (no daytime sleep) to 24 (worst daytime sleep). |
Countries
China
Participant flow
Pre-assignment details
Whilst 475 patients were enrolled only 473 were treated, since one patient was not compliant to protocol and did not take any trial drug and another refused to take trial medication.
Participants by arm
| Arm | Count |
|---|---|
| Pramipexole ER Pramipexole Extended Release (ER). Tablets of 0.375 mg and 1.5 mg administered once daily (qd) to achieve daily doses of 0.375 mg, 0.75 mg, 1.5 mg, 2.25 mg, 3.0 mg, 3.75 mg or 4.5 mg | 234 |
| Pramipexole IR Pramipexole Immediate Release (IR). Tablets of 0.125 mg, 0.25 mg and 1.0 mg administered 3 times daily to achieve a total daily dose of 0.375 mg, 0.75 mg, 1.5 mg, 2.25 mg, 3.0 mg, 3.75 mg, or 4.5 mg | 239 |
| Total | 473 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 11 | 12 |
| Overall Study | Other | 1 | 3 |
| Overall Study | Protocol Violation | 1 | 2 |
| Overall Study | Withdrawal by Subject | 4 | 2 |
Baseline characteristics
| Characteristic | Pramipexole ER | Pramipexole IR | Total |
|---|---|---|---|
| Age, Continuous | 62.2 years STANDARD_DEVIATION 9.1 | 61.8 years STANDARD_DEVIATION 9.03 | 62.0 years STANDARD_DEVIATION 9.06 |
| Sex: Female, Male Female | 80 Participants | 95 Participants | 175 Participants |
| Sex: Female, Male Male | 154 Participants | 144 Participants | 298 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 93 / 234 | 90 / 239 |
| serious Total, serious adverse events | 6 / 234 | 13 / 239 |
Outcome results
Primary
Change From Baseline in Unified Parkinsons Disease Rating Scale (UPDRS) Parts II+III Score at Week 18
UPDRS total score ranges from 0 (best) to 160 (worst) and was calculated as the sum of Part II (activities of daily living, ranges from 0 to 52) and Part III (motor examination, ranges from 0 to 108). Reduction over time represents an improvement. Means are adjusted for treatment, centre and baseline.
Time frame: Baseline and week 18
Population: Full analysis set (FAS) with last observation carried forward (LOCF). FAS is defined as all randomised patients which received at least one dose of study drug and provided any post baseline efficacy assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole ER | Change From Baseline in Unified Parkinsons Disease Rating Scale (UPDRS) Parts II+III Score at Week 18 | -13.807 Units on a scale | Standard Error 0.6547 |
| Pramipexole IR | Change From Baseline in Unified Parkinsons Disease Rating Scale (UPDRS) Parts II+III Score at Week 18 | -13.047 Units on a scale | Standard Error 0.6434 |
Comparison: The null hypothesis (H0) states that the mean change from baseline to Week 18 (or last observation carried forward \[LOCF\]) in the UPDRS II+III score for the treatment group pramipexole ER is inferior to the mean change for the treatment group pramipexole IR.p-value: <0.000195% CI: [-1.047, 2.566]ANCOVA
Secondary
Change From Baseline in Duration of Off-time During Waking Hours at Week 18
Duration of off-time during waking hours based on patient diary data. Off-time describes a period when the patient experiences increased parkinsonian symptoms (e.g. immobility or inability to move with ease). Reduction over time represents an improvement. Means are adjusted for treatment, centre and baseline.
Time frame: Baseline and week 18
Population: FAS (LOCF) reduced to patients with advanced PD. Advanced PD patients were those reporting at least 2 hours of off-time daily during each of the two days before baseline, as recorded in the patient diary.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole ER | Change From Baseline in Duration of Off-time During Waking Hours at Week 18 | -1.044 hours | Standard Error 0.2256 |
| Pramipexole IR | Change From Baseline in Duration of Off-time During Waking Hours at Week 18 | -1.098 hours | Standard Error 0.23 |
p-value: 0.869895% CI: [-0.699, 0.592]ANCOVA
Secondary
Change From Baseline in Duration of On-time With Non-troublesome Dyskinesia at Week 18
Duration on-time with non-troublesome Dyskinesia based on patient diary data, percentage ranging from 0 (worst case) to 100 (best case). On-time describes a period during which a patient was relatively free of Parkinsons symptoms (e.g. mobile or capable of moving with relative ease and independence). Dyskinesia qualified as non-troublesome if it did not interfere with function or did not cause meaningful discomfort. Increase in the duration represents an improvement. Means are adjusted for treatment, centre and baseline.
Time frame: Baseline and week 18
Population: FAS (LOCF) reduced to patients with advanced PD. Advanced PD patients were those reporting at least 2 hours of off-time daily during each of the two days before baseline, as recorded in the patient diary.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole ER | Change From Baseline in Duration of On-time With Non-troublesome Dyskinesia at Week 18 | -0.044 hours | Standard Error 0.174 |
| Pramipexole IR | Change From Baseline in Duration of On-time With Non-troublesome Dyskinesia at Week 18 | 0.518 hours | Standard Error 0.1773 |
p-value: 0.026395% CI: [0.067, 1.057]ANCOVA
Secondary
Change From Baseline in Duration of On-time Without Dyskinesia at Week 18
Duration of on-time without Dyskinesia based on patient diary data. On-time describes a period during which a patient was relatively free of Parkinsons symptoms (e.g. mobile or capable of moving with relative ease and independence). Increase in the duration represents an improvement. Means are adjusted for treatment, centre and baseline.
Time frame: Baseline and week 18
Population: FAS (LOCF) reduced to patients with advanced PD. Advanced PD patients were those reporting at least 2 hours of off-time daily during each of the two days before baseline, as recorded in the patient diary.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole ER | Change From Baseline in Duration of On-time Without Dyskinesia at Week 18 | 1.026 hours | Standard Error 0.3076 |
| Pramipexole IR | Change From Baseline in Duration of On-time Without Dyskinesia at Week 18 | 0.496 hours | Standard Error 0.3134 |
p-value: 0.233895% CI: [-1.405, 0.345]ANCOVA
Secondary
Change From Baseline in Duration of On-time Without or With Non-troublesome Dyskinesia at Week 18
Duration of on-time without Dyskinesia or with non-troublesome Dyskinesia based on patient diary data, percentage ranging from 0 (worst case) to 100 (best case). On-time describes a period during which a patient was relatively free of Parkinsons symptoms (e.g. mobile or capable of moving with relative ease and independence). Dyskinesia qualified as non-troublesome if it did not interfere with function or did not cause meaningful discomfort. Increase in the duration represents an improvement. Means are adjusted for treatment, centre and baseline.
Time frame: Baseline and week 18
Population: FAS (LOCF) reduced to patients with advanced PD. Advanced PD patients were those reporting at least 2 hours of off-time daily during each of the two days before baseline, as recorded in the patient diary.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole ER | Change From Baseline in Duration of On-time Without or With Non-troublesome Dyskinesia at Week 18 | 0.982 hours | Standard Error 0.2583 |
| Pramipexole IR | Change From Baseline in Duration of On-time Without or With Non-troublesome Dyskinesia at Week 18 | 1.013 hours | Standard Error 0.2632 |
p-value: 0.933795% CI: [-0.704, 0.766]ANCOVA
Secondary
Change From Baseline in Duration of On-time With Troublesome Dyskinesia at Week 18
Duration of on-time with troublesome Dyskinesia based on patient diary data, percentage ranging from 0 (best case) to 100 (worst case). On-time describes a period during which a patient was relatively free of Parkinsons symptoms (e.g. mobile or capable of moving with relative ease and independence). Dyskinesia qualified as troublesome if it interfered with function or caused meaningful discomfort. Decrease in the duration represents an improvement. Means are adjusted for treatment, centre and baseline.
Time frame: Baseline and week 18
Population: FAS (LOCF) reduced to patients with advanced PD. Advanced PD patients were those reporting at least 2 hours of off-time daily during each of the two days before baseline, as recorded in the patient diary.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole ER | Change From Baseline in Duration of On-time With Troublesome Dyskinesia at Week 18 | -0.000 hours | Standard Error 0.0553 |
| Pramipexole IR | Change From Baseline in Duration of On-time With Troublesome Dyskinesia at Week 18 | 0.031 hours | Standard Error 0.0564 |
p-value: 0.699595% CI: [-0.127, 0.188]ANCOVA
Secondary
Change From Baseline in Percentage Off-time During Waking Hours at Week 18
Percentage off-time during waking hours based on patient diary data, percentage ranging from 0 (best case) to 100 (worst case). Off-time describes a period when the patient experiences increased parkinsonian symptoms (e.g. immobility or inability to move with ease). Reduction over time represents an improvement. Means are adjusted for treatment, centre and baseline.
Time frame: Baseline and week 18
Population: FAS (LOCF) reduced to patients with advanced Parkinsons Disease (PD). Advanced PD patients were those reporting at least 2 hours of off-time daily during each of the two days before baseline, as recorded in the patient diary.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole ER | Change From Baseline in Percentage Off-time During Waking Hours at Week 18 | -6.962 Percentage off-time | Standard Error 1.5072 |
| Pramipexole IR | Change From Baseline in Percentage Off-time During Waking Hours at Week 18 | -7.443 Percentage off-time | Standard Error 1.5362 |
p-value: 0.826195% CI: [-4.787, 3.826]ANCOVA
Secondary
Change From Baseline in Percentage On-time With Non-troublesome Dyskinesia at Week 18
Percentage on-time with non-troublesome Dyskinesia based on patient diary data, percentage ranging from 0 (worst case) to 100 (best case). On-time describes a period during which a patient was relatively free of Parkinsons symptoms (e.g. mobile or capable of moving with relative ease and independence). Dyskinesia qualified as non-troublesome if it did not interfere with function or did not cause meaningful discomfort. Increase in the percentage represents an improvement. Means are adjusted for treatment, centre and baseline.
Time frame: Baseline and week 18
Population: FAS (LOCF) reduced to patients with advanced PD. Advanced PD patients were those reporting at least 2 hours of off-time daily during each of the two days before baseline, as recorded in the patient diary.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole ER | Change From Baseline in Percentage On-time With Non-troublesome Dyskinesia at Week 18 | -0.235 Percentage of on-time | Standard Error 1.0807 |
| Pramipexole IR | Change From Baseline in Percentage On-time With Non-troublesome Dyskinesia at Week 18 | 3.275 Percentage of on-time | Standard Error 1.1013 |
p-value: 0.025495% CI: [0.437, 6.583]ANCOVA
Secondary
Change From Baseline in Percentage On-time Without Dyskinesia at Week 18
Percentage on-time without Dyskinesia based on patient diary data, percentage ranging from 0 (worst case) to 100 (best case). On-time describes a period during which a patient was relatively free of Parkinsons symptoms (e.g. mobile or capable of moving with relative ease and independence). Increase in the percentage represents an improvement. Means are adjusted for treatment, centre and baseline.
Time frame: Baseline and week 18
Population: FAS (LOCF) reduced to patients with advanced PD. Advanced PD patients were those reporting at least 2 hours of off-time daily during each of the two days before baseline, as recorded in the patient diary.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole ER | Change From Baseline in Percentage On-time Without Dyskinesia at Week 18 | 7.028 Percentage of on-time | Standard Error 1.9274 |
| Pramipexole IR | Change From Baseline in Percentage On-time Without Dyskinesia at Week 18 | 4.265 Percentage of on-time | Standard Error 1.9643 |
p-value: 0.322395% CI: [-8.255, 2.729]ANCOVA
Secondary
Change From Baseline in Percentage On-time Without or With Non-troublesome Dyskinesia at Week 18
Percentage on-time without or with non-troublesome Dyskinesia based on patient diary data, percentage ranging from 0 (best case) to 100 (worst case). On-time describes a period during which a patient was relatively free of Parkinsons symptoms (e.g. mobile or capable of moving with relative ease and independence). Dyskinesia qualified as non-troublesome if it did not interfere with function or did not cause meaningful discomfort. Increase in the percentage represents an improvement. Means are adjusted for treatment, centre and baseline.
Time frame: Baseline and week 18
Population: FAS (LOCF) reduced to patients with advanced PD. Advanced PD patients were those reporting at least 2 hours of off-time daily during each of the two days before baseline, as recorded in the patient diary.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole ER | Change From Baseline in Percentage On-time Without or With Non-troublesome Dyskinesia at Week 18 | 6.855 Percentage of on-time | Standard Error 1.5672 |
| Pramipexole IR | Change From Baseline in Percentage On-time Without or With Non-troublesome Dyskinesia at Week 18 | 7.476 Percentage of on-time | Standard Error 1.5973 |
p-value: 0.784395% CI: [-3.848, 5.09]ANCOVA
Secondary
Change From Baseline in Percentage On-time With Troublesome Dyskinesia at Week 18
Percentage on-time with troublesome Dyskinesia based on patient diary data, percentage ranging from 0 (best case) to 100 (worst case). On-time describes a period during which a patient was relatively free of Parkinsons symptoms (e.g. mobile or capable of moving with relative ease and independence). Dyskinesia qualified as troublesome if it interfered with function or caused meaningful discomfort. Decrease in the percentage represents an improvement. Means are adjusted for treatment, centre and baseline.
Time frame: Baseline and week 18
Population: FAS (LOCF) reduced to patients with advanced PD. Advanced PD patients were those reporting at least 2 hours of off-time daily during each of the two days before baseline, as recorded in the patient diary.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole ER | Change From Baseline in Percentage On-time With Troublesome Dyskinesia at Week 18 | -0.142 Percentage of on-time | Standard Error 0.3398 |
| Pramipexole IR | Change From Baseline in Percentage On-time With Troublesome Dyskinesia at Week 18 | 0.226 Percentage of on-time | Standard Error 0.3463 |
p-value: 0.452995% CI: [-0.598, 1.335]ANCOVA
Secondary
Change From Baseline in UPDRS III Score Separately at Week 18
UPDRS Part III (motor examination) ranges from 0 to 108. Reduction over time represents an improvement. Means are adjusted for treatment, centre and baseline.
Time frame: Baseline and week 18
Population: FAS (LOCF)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole ER | Change From Baseline in UPDRS III Score Separately at Week 18 | -10.068 Units on a scale | Standard Error 0.5048 |
| Pramipexole IR | Change From Baseline in UPDRS III Score Separately at Week 18 | -9.440 Units on a scale | Standard Error 0.4962 |
p-value: 0.37695% CI: [-0.765, 2.021]ANCOVA
Secondary
Change From Baseline in UPDRS II Score Separately at Week 18
UPDRS Part II (activities of daily living) ranges from 0 to 52. Reduction over time represents an improvement. Means are adjusted for treatment, centre and baseline.
Time frame: Baseline and week 18
Population: FAS (LOCF)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole ER | Change From Baseline in UPDRS II Score Separately at Week 18 | -3.750 Units on a scale | Standard Error 0.2235 |
| Pramipexole IR | Change From Baseline in UPDRS II Score Separately at Week 18 | -3.596 Units on a scale | Standard Error 0.2197 |
p-value: 0.623795% CI: [-0.463, 0.771]ANCOVA
Secondary
Clinical Global Impression of Improvement (CGI-I) Responder at Week 18
CGI-I was used to assess the overall status of Parkinsons disease (PD) after interviewing the patient about the various aspects of the PD and after evaluating adverse events and concomitant treatments. Ranging from 1 point=very much improved to 7 points=very much worse. Responders were defined as patients having score 1 or 2 (at least much improved) when comparing the past week to the assessment at baseline.
Time frame: 18 weeks
Population: FAS (LOCF). Only patients with on-treatment CGI-I evaluation were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pramipexole ER | Clinical Global Impression of Improvement (CGI-I) Responder at Week 18 | Responder | 125 Participants |
| Pramipexole ER | Clinical Global Impression of Improvement (CGI-I) Responder at Week 18 | Non-Responder | 99 Participants |
| Pramipexole IR | Clinical Global Impression of Improvement (CGI-I) Responder at Week 18 | Responder | 138 Participants |
| Pramipexole IR | Clinical Global Impression of Improvement (CGI-I) Responder at Week 18 | Non-Responder | 95 Participants |
p-value: 0.317Cochran-Mantel-Haenszel
Secondary
Levodopa (L-Dopa) Dose Change During the Study
Although the number of patients who began the study with concomitant L-dopa supplementation and required a change in dosage was not analysed for this study, the change from baseline in L-dopa dose is presented.
Time frame: 18 weeks
Population: FAS. Only patients with concomitant L-Dopa treatment at baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole ER | Levodopa (L-Dopa) Dose Change During the Study | -5.17 mg | Standard Deviation 51.563 |
| Pramipexole IR | Levodopa (L-Dopa) Dose Change During the Study | -11.22 mg | Standard Deviation 101.913 |
Secondary
Levodopa (L-Dopa) Introduction During the Study
Number of patients without concomitant L-Dopa treatment at baseline which required L-Dopa supplementation during the study.
Time frame: 18 weeks
Population: FAS. Only patients without concomitant L-Dopa treatment at baseline.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pramipexole ER | Levodopa (L-Dopa) Introduction During the Study | with L-Dopa introduction | 1 Participants |
| Pramipexole ER | Levodopa (L-Dopa) Introduction During the Study | without L-Dopa introduction | 24 Participants |
| Pramipexole IR | Levodopa (L-Dopa) Introduction During the Study | with L-Dopa introduction | 0 Participants |
| Pramipexole IR | Levodopa (L-Dopa) Introduction During the Study | without L-Dopa introduction | 40 Participants |
Secondary
Patient Global Impressions of Improvement (PGI-I) Responder at Week 18
The PGI-I scale is a patient-rated instrument which was used to measure the improvement of a patients PD symptoms throughout the study. Ranging from 1 point=very much better to 7 points=very much worse. Responders were defined as patients having score 1 or 2 (at least much better) when comparing the past week to the assessment at baseline.
Time frame: 18 weeks
Population: FAS (LOCF)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pramipexole ER | Patient Global Impressions of Improvement (PGI-I) Responder at Week 18 | Responder | 119 Participants |
| Pramipexole ER | Patient Global Impressions of Improvement (PGI-I) Responder at Week 18 | Non-Responder | 109 Participants |
| Pramipexole IR | Patient Global Impressions of Improvement (PGI-I) Responder at Week 18 | Responder | 127 Participants |
| Pramipexole IR | Patient Global Impressions of Improvement (PGI-I) Responder at Week 18 | Non-Responder | 109 Participants |
p-value: 0.4756Cochran-Mantel-Haenszel
Secondary
Responder in Percentage Off-time During Waking Hours at Week 18
Percentage off-time based on patient diary data, percentage ranging from 0 (best case) to 100 (worst case). Off-time describes a period when the patient experiences increased parkinsonian symptoms (e.g. immobility or inability to move with ease). Reduction over time represents an improvement. Responders were defined as patients with at least a 20 percent improvement relative to baseline.
Time frame: Baseline and week 18
Population: FAS (LOCF) reduced to patients with advanced PD. Advanced PD patients were those reporting at least 2 hours of off-time daily during each of the two days before baseline, as recorded in the patient diary.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pramipexole ER | Responder in Percentage Off-time During Waking Hours at Week 18 | Responder | 58 Participants |
| Pramipexole ER | Responder in Percentage Off-time During Waking Hours at Week 18 | Non-Responder | 52 Participants |
| Pramipexole IR | Responder in Percentage Off-time During Waking Hours at Week 18 | Responder | 59 Participants |
| Pramipexole IR | Responder in Percentage Off-time During Waking Hours at Week 18 | Non-Responder | 47 Participants |
p-value: 0.7902Cochran-Mantel-Haenszel
Secondary
Responder in UPDRS Parts II+III Score at Week 18
Responders were defined as patients with at least a 20 percent improvement of UPDRS II+III score relative to baseline. UPDRS II+III ranges 0-160 scores from best to worst and was calculated as the sum of Part II (activities of daily living, ranges from 0 to 52) and Part III (motor examination, ranges from 0 to 108).
Time frame: Baseline and week 18
Population: FAS (LOCF)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pramipexole ER | Responder in UPDRS Parts II+III Score at Week 18 | Responder | 164 Participants |
| Pramipexole ER | Responder in UPDRS Parts II+III Score at Week 18 | Non-Responder | 64 Participants |
| Pramipexole IR | Responder in UPDRS Parts II+III Score at Week 18 | Responder | 154 Participants |
| Pramipexole IR | Responder in UPDRS Parts II+III Score at Week 18 | Non-Responder | 82 Participants |
p-value: 0.1051Cochran-Mantel-Haenszel
Other Pre-specified
Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score at 18 Weeks
ESS is a patient-report scale with 8 items rating how likely one is to fall asleep during passive and inconsequential situations such as watching television, more active situations such as sitting and talking to someone, or consequential situations such as sitting in a car, while stopped for a few minutes in traffic. The likelihood of dozing off is rated from 0 points (no chance) to 3 points (high chance). The overall rating scale is scored from 0 (no daytime sleep) to 24 (worst daytime sleep).
Time frame: Baseline and week 18
Population: Observed cases (OC). Only patients with ESS assessment at baseline and at 18 weeks were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole ER | Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score at 18 Weeks | 0.1 Units on a scale | Standard Deviation 3.43 |
| Pramipexole IR | Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score at 18 Weeks | -0.0 Units on a scale | Standard Deviation 3.38 |