Parkinson Disease
Conditions
Brief summary
The objective of this trial is to investigate the safety, tolerability, trough plasma concentration, and efficacy of pramipexole ER in comparison with those of pramipexole IR administrated orally for 12 weeks in patients with PD on levodopa (L-DOPA) therapy (the double-blind period). The double-blind period will be followed by the open-label 52 week administration of pramipexole ER to evaluate the long term safety and efficacy (the open-label period).
Interventions
titrated as individually needed (0.25 mg - 4.5 mg daily)
titration as individually needed (0.375 mg -4.5 mg daily)
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
1 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female patients with diagnosis of PD including juvenile Parkinsonism, in whom the onset began at the age of forty or younger. 2. Patients with a modified Hoehn and Yahr scale of II to IV at on time. 3. Patients who have received an individual dosage of L-DOPA (either standard L-DOPA or L-DOPA with dopa-decarboxylase inhibitor) at a stable dose for at least 4 weeks before the baseline visit (Visit 2). 4. Patients who exhibit any therapeutically problematic issues or status based on L-DOPA therapy: * wearing-off phenomena * no on /delayed on * dystonia at off time * on-off phenomena * freezing phenomena at off time * the sub-optimal dose of L-DOPA had been administered due to side effects (such as dyskinesia), or therapeutical strategy
Exclusion criteria
1. Atypical parkinsonian syndromes due to drugs, metabolic disorders, encephalitis or degenerative diseases. 2. Dementia, as defined by a Mini-Mental State Examination (MMSE) score \<24 at screening visit. 3. Any psychiatric disorder according to DSM-IV criteria that could prevent compliance or completion of the trial and/or put the patient at risk if he/she takes part in the trial. 4. History of psychosis, except history of drug induced hallucinations (provided the investigator considers that participation in the trial would not represent a significant risk for the patient). 5. Clinically significant ECG abnormalities at screening visit, according to investigator's judgement. 6. Clinically significant hypotension or symptomatic orthostatic hypotension (i.e., clinical symptoms of orthostatic hypotension such as dizziness postural etc 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) either at screening visit or at baseline visit. 7. Any other clinically significant disease, whether treated or not, that could put the patient at risk or could prevent compliance or completion of the trial. 8. Pregnancy (to be excluded by serum pregnancy test at screening visit) or breast-feeding. 9. Sexually active female of childbearing potential not using a medically approved method of birth control within one month before to the screening visit and throughout the trial period. 10. Serum levels of AST, ALT, alkaline phosphatases or bilirubin \>2 upper limits of normal . 11. Patients with a creatinine clearance \<50 mL/min 12. Patients with a complication or signs of malignant tumours or those within 5 years after the treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experienced Adverse Events | 12 weeks | An adverse event is defined as any untoward medical occurrence |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Percentage Off-time | baseline and after 12 weeks treatment | Percentage off-time during waking hours in the last two days 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). |
| Change From Baseline in Percentage On-time Without Dyskinesia | baseline and after 12 weeks treatment | Percentage on-time without dyskinesia during waking hours in the last two days based on patient diary data, percentage ranging from 0 (worst case) to 100 (best case). On-time describes a period when the patient has no symptoms of off-time and is not asleep. |
| Change From Baseline in Percentage On-time With Non-troublesome Dyskinesia | baseline and after 12 weeks treatment | Percentage on-time with non-troublesome dyskinesia during waking hours in the last two days based on patient diary data, percentage ranging from 0(worst case) to 100 (best case). On-time describes a period when the patient has no symptoms of off-time and is not asleep. |
| Change From Baseline in Percentage On-time Without Dyskinesia or With Non-troublesome Dyskinesia | baseline and after 12 weeks treatment | Percentage on-time without dyskinesia or non-troublesome dyskinesia during waking hours in the last two days based on patient diary data, percentage ranging from 0 (worst case) to 100 (best case). On-time describes a period when the patient has no symptoms of off-time and is not asleep. |
| Change From Baseline in Percentage On-time With Troublesome Dyskinesia | baseline and after 12 weeks treatment | Percentage on-time with troublesome dyskinesia during waking hours in the last two days based on patient diary data, percentage ranging from 0 (best case) to 100 (worst case). On-time describes a period when the patient has no symptoms of off-time and is not asleep. |
| Responder Rate For Clinical Global Impression of Improvement (CGI-I) | baseline and after 12 weeks treatment | CGI-I scores ranging from '1' (very much improved) to '7' (very much worse), CGI-I responder have scoring of 1 or 2 (at least much improved) |
| Responder Rate For Patient Global Impression of Improvement (PGI-I) | baseline and after 12 weeks treatment | PGI-I scores ranging from '1' (very much better) to '7' (very much worse), PGI-I responder have scoring of 1 or 2 (at least much better) |
| Change From Baseline in UPDRS Part I Score | baseline and after 12 weeks treatment | UPDRS Part I ranging from 0 (normal) to 16 (severe). UPDRS Part I measures Mentation, Behavior and Mood |
| Change From Baseline in UPDRS Part II Score | baseline and after 12 weeks treatment | UPDRS Part II ranging from 0 (normal) to 52 (severe). UPDRS Part II is calculated as the average of UPDRS Part II at on and UPDRS Part II at off-period for each of the 13 activities. |
| Change From Baseline in UPDRS Part III Score | baseline and after 12 weeks treatment | UPDRS Part III ranging from 0 (normal) to 108 (severe). UPDRS Part III measures motor symptoms |
| Change From Baseline in UPDRS Part IV Score | baseline and after 12 weeks treatment | UPDRS Part IV ranging from 0 (normal) to 23 (severe). UPDRS Part IV measures complications of therapy |
| UPDRS Parts II+III Total Score Responder Rate (at Least 20% Improvement) | baseline and after 12 weeks treatment | Responders are defined as at least 20% decrease in the UPDRS Parts II+III Total Score ranges 0-160 scores from best to worse |
| Change From Baseline in L-dopa Daily Dose | baseline and after 12 weeks treatment | The L-dopa daily dose was recorded in the electronic case report form (eCRF) at each trial visit. |
| Trough Plasma Concentration at Steady State | at Visit 8 after pramipexole ER 4.5mg and IR 4.5mg treatment | Geometric mean (gMean) was calculated for trough plasma concentrations of pramipexole at steady state after administration of pramipexole IR 4.5mg and pramipexole ER 4.5mg. |
| Dose Proportionality of Trough Plasma Concentration at Steady State After Pramipexole ER Treatment | from Visit 1 to Visit 8 after pramipexole ER | Dose proportionality of trough plasma concentrations at steady state is explored by using the power model that described the functional relationship between the dose and plasma concentration |
| Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Parts II+III Total Score | baseline and after 12 weeks treatment | UPDRS II+III ranging from 0 point(normal) to 160 point (severe). UPDRS part II measures activities of daily living, part III measures motor symptoms |
| Percentage of Patients With no Worsening of UPDRS Parts II+III Total Score by More Than 15% From Week 12 to Week 16 (Open-label: Dose Adjustment Phase) | Week 12 to Week 16 | Percentage of patients with no worsening of UPDRS Parts II+III Total Score by more than 15% from week 12 to week 16 (Open-label: Dose Adjustment Phase) |
| Clinical Global Impression of Improvement (CGI-I) at Week 16 Compared to Patient's CGI-I Status at Week 12 (Open-label: Dose Adjustment Phase) | Week 12 to Week 16 | Clinical Global Impression of Improvement (CGI-I) at week 16 compared to patient's CGI-I status at week 12. CGI-I scores ranging from '1' (very much improved) to '7' (very much worse) |
| Patient Global Impression of Improvement (PGI-I) at Week 16 Compared to Patient's PGI-I Status at Week 12 (Open-label: Dose Adjustment Phase) | Week 12 to Week 16 | Patient Global Impression of Improvement (PGI-I) at week 16 compared to patient's PGI-I status at week 12. PGI-I scores ranging from '1' (very much better) to '7' (very much worse). |
| Change From Baseline in UPDRS (Unified Parkinson's Disease Rating Scale) Parts II+III Total Score (Open-label: Maintenance Phase) | Baseline and after 64 weeks treatment | UPDRS II+III ranging from 0 point(normal) to 160 point (severe). UPDRS part II measures activities of daily living, part III measures motor symptoms |
| UPDRS Parts II+III Total Score Responder Rate (at Least 20% Improvement) (Open-label: Maintenance Phase) | baseline and after 64 weeks treatment | Responders are defined as at least 20% decrease in the UPDRS Parts II+III Total Score ranges 0-160 scores from best to worse |
| Change From Baseline in Percentage Off-time (Open-label: Maintenance Phase) | baseline and after 64 weeks treatment | Percentage off-time during waking hours in the last two days 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). |
| Change From Baseline in Percentage On-time Without Dyskinesia (Open-label: Maintenance Phase) | baseline and after 64 weeks treatment | Percentage on-time without dyskinesia during waking hours in the last two days based on patient diary data, percentage ranging from 0 (worst case) to 100 (best case). On-time describes a period when the patient has no symptoms of off-time and is not asleep. |
| Change From Baseline in Percentage On-time With Non-troublesome Dyskinesia (Open-label Maintenance Phase) | baseline and after 64 weeks treatment | Percentage on-time with non-troublesome dyskinesia during waking hours in the last two days based on patient diary data, percentage ranging from 0(worst case) to 100 (best case). On-time describes a period when the patient has no symptoms of off-time and is not asleep. |
| Change From Baseline in Percentage On-time Without Dyskinesia or With Non-troublesome Dyskinesia (Open-label Maintenance Phase) | baseline and after 64 weeks treatment | Percentage on-time without dyskinesia or non-troublesome dyskinesia during waking hours in the last two days based on patient diary data, percentage ranging from 0 (worst case) to 100 (best case). On-time describes a period when the patient has no symptoms of off-time and is not asleep. |
| Change From Baseline in Percentage On-time With Troublesome Dyskinesia (Open-label Maintenance Phase) | baseline and after 64 weeks treatment | Percentage on-time with troublesome dyskinesia during waking hours in the last two days based on patient diary data, percentage ranging from 0 (best case) to 100 (worst case). On-time describes a period when the patient has no symptoms of off-time and is not asleep. |
| Change From Baseline in L-dopa Daily Dose (Open-label Maintenance Phase) | baseline and after 64 weeks treatment | The L-dopa daily dose was recorded in the electronic case report form (eCRF) at each trial visit. |
| Change From Baseline in UPDRS Part I Score (Open-label: Maintenance Phase) | baseline and after 64 weeks treatment | UPDRS Part I ranging from 0 (normal) to 16 (severe). UPDRS Part I measures Mentation, Behavior and Mood |
| Change From Baseline in UPDRS Part II Score (Open-label: Maintenance Phase) | baseline and after 64 weeks treatment | UPDRS Part II ranging from 0 (normal) to 52 (severe). UPDRS Part II is calculated as the average of UPDRS Part II at on and UPDRS Part II at off-period for each of the 13 activities. |
| Change From Baseline in UPDRS Part III Score (Open-label: Maintenance Phase) | baseline and after 64 weeks treatment | UPDRS Part III ranging from 0 (normal) to 108 (severe). UPDRS Part III measures motor symptoms |
| Change From Baseline in UPDRS Part IV Score (Open-label: Maintenance Phase) | baseline and after 64 weeks treatment | UPDRS Part IV ranging from 0 (normal) to 23 (severe). UPDRS Part IV measures complications of therapy |
| Change From End of Double-Blind Period in UPDRS (Unified Parkinson's Disease Rating Scale) Parts II+III Total Score (Open-label: Dose Adjustment Phase) | Week 12 to Week 16 | UPDRS II+III ranging from 0 point(normal) to 160 point (severe). UPDRS part II measures activities of daily living, part III measures motor symptoms. Least square means and standard errors presented are from ANCOVA with factors treatment and covariate baseline. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pramipexole Extended Release Group (PPX ER) Pramipexole ER (tablets of 0.375 mg and 1.5 mg) dose: 0.375 mg, 0.75 mg, 1.5 mg, 2.25 mg, 3.0 mg, 3.75 mg, or 4.5 mg, once a day | 56 |
| Pramipexole Immediate Release Group (PPX IR) Pramipexole IR (tablets of 0.125 mg and 0.5 mg) dose: 0.25 mg, 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg, 2.5 mg, 3.0 mg, 3.5 mg, or 4.5 mg, twice or three times a day | 56 |
| Total | 112 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 12 Week Double-blind Period | Adverse Event | 3 | 2 |
| 12 Week Double-blind Period | Protocol Violation | 1 | 0 |
| 12 Week Double-blind Period | Withdrawal by Subject | 1 | 1 |
| 52-week Open-label Period Pramipexole ER | Adverse Event | 6 | 6 |
| 52-week Open-label Period Pramipexole ER | Lack of Efficacy | 1 | 1 |
| 52-week Open-label Period Pramipexole ER | Other reason - investigator's judgement | 1 | 1 |
| 52-week Open-label Period Pramipexole ER | Withdrawal by Subject | 0 | 3 |
Baseline characteristics
| Characteristic | Pramipexole Extended Release Group (PPX ER) | Pramipexole Immediate Release Group (PPX IR) | Total |
|---|---|---|---|
| Age, Continuous | 68.8 years STANDARD_DEVIATION 8 | 66.1 years STANDARD_DEVIATION 7.5 | 67.5 years STANDARD_DEVIATION 7.8 |
| Sex: Female, Male Female | 35 Participants | 35 Participants | 70 Participants |
| Sex: Female, Male Male | 21 Participants | 21 Participants | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 52 / 56 | 49 / 56 |
| serious Total, serious adverse events | 12 / 56 | 10 / 56 |
Outcome results
Primary
Percentage of Participants Who Experienced Adverse Events
An adverse event is defined as any untoward medical occurrence
Time frame: 12 weeks
Population: Treated set for safety, which was the analysis set including all the patients who had valid measurements after drug administration.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pramipexole Extended Release Group (PPX ER) | Percentage of Participants Who Experienced Adverse Events | 83.93 percentage of participants |
| Pramipexole Immediate Release Group (PPX IR) | Percentage of Participants Who Experienced Adverse Events | 83.93 percentage of participants |
Secondary
Change From Baseline in L-dopa Daily Dose
The L-dopa daily dose was recorded in the electronic case report form (eCRF) at each trial visit.
Time frame: baseline and after 12 weeks treatment
Population: Full Analysis Set (FAS) with last observation carried forward (LOCF)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole Extended Release Group (PPX ER) | Change From Baseline in L-dopa Daily Dose | -5.3 mg per day | Standard Error 3 |
| Pramipexole Immediate Release Group (PPX IR) | Change From Baseline in L-dopa Daily Dose | -1.8 mg per day | Standard Error 3 |
Secondary
Change From Baseline in L-dopa Daily Dose (Open-label Maintenance Phase)
The L-dopa daily dose was recorded in the electronic case report form (eCRF) at each trial visit.
Time frame: baseline and after 64 weeks treatment
Population: Full Analysis Set (FAS 2) for open label period with observed case (OC)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole Extended Release Group (PPX ER) | Change From Baseline in L-dopa Daily Dose (Open-label Maintenance Phase) | 10.3 mg per day | Standard Deviation 62 |
Secondary
Change From Baseline in Percentage Off-time
Percentage off-time during waking hours in the last two days 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).
Time frame: baseline and after 12 weeks treatment
Population: Full Analysis Set (FAS) with last observation carried forward (LOCF)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole Extended Release Group (PPX ER) | Change From Baseline in Percentage Off-time | -5.8 Percentage of off-time | Standard Error 2.4 |
| Pramipexole Immediate Release Group (PPX IR) | Change From Baseline in Percentage Off-time | -7.8 Percentage of off-time | Standard Error 2.4 |
Secondary
Change From Baseline in Percentage Off-time (Open-label: Maintenance Phase)
Percentage off-time during waking hours in the last two days 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).
Time frame: baseline and after 64 weeks treatment
Population: Full Analysis Set (FAS 2) for open label period with observed case (OC)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole Extended Release Group (PPX ER) | Change From Baseline in Percentage Off-time (Open-label: Maintenance Phase) | -11.6 Percentage of off-time | Standard Deviation 22.1 |
Secondary
Change From Baseline in Percentage On-time With Non-troublesome Dyskinesia
Percentage on-time with non-troublesome dyskinesia during waking hours in the last two days based on patient diary data, percentage ranging from 0(worst case) to 100 (best case). On-time describes a period when the patient has no symptoms of off-time and is not asleep.
Time frame: baseline and after 12 weeks treatment
Population: Full Analysis Set (FAS) with last observation carried forward (LOCF)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole Extended Release Group (PPX ER) | Change From Baseline in Percentage On-time With Non-troublesome Dyskinesia | -0.4 Percentage of on-time | Standard Error 0.4 |
| Pramipexole Immediate Release Group (PPX IR) | Change From Baseline in Percentage On-time With Non-troublesome Dyskinesia | 0.1 Percentage of on-time | Standard Error 0.4 |
Secondary
Change From Baseline in Percentage On-time With Non-troublesome Dyskinesia (Open-label Maintenance Phase)
Percentage on-time with non-troublesome dyskinesia during waking hours in the last two days based on patient diary data, percentage ranging from 0(worst case) to 100 (best case). On-time describes a period when the patient has no symptoms of off-time and is not asleep.
Time frame: baseline and after 64 weeks treatment
Population: Full Analysis Set (FAS 2) for open label period with observed case (OC)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole Extended Release Group (PPX ER) | Change From Baseline in Percentage On-time With Non-troublesome Dyskinesia (Open-label Maintenance Phase) | -0.1 Percentage of on-time | Standard Deviation 5.7 |
Secondary
Change From Baseline in Percentage On-time Without Dyskinesia
Percentage on-time without dyskinesia during waking hours in the last two days based on patient diary data, percentage ranging from 0 (worst case) to 100 (best case). On-time describes a period when the patient has no symptoms of off-time and is not asleep.
Time frame: baseline and after 12 weeks treatment
Population: Full Analysis Set (FAS) with last observation carried forward (LOCF)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole Extended Release Group (PPX ER) | Change From Baseline in Percentage On-time Without Dyskinesia | 6.4 Percentage of on-time | Standard Error 2.5 |
| Pramipexole Immediate Release Group (PPX IR) | Change From Baseline in Percentage On-time Without Dyskinesia | 7.0 Percentage of on-time | Standard Error 2.5 |
Secondary
Change From Baseline in Percentage On-time Without Dyskinesia (Open-label: Maintenance Phase)
Percentage on-time without dyskinesia during waking hours in the last two days based on patient diary data, percentage ranging from 0 (worst case) to 100 (best case). On-time describes a period when the patient has no symptoms of off-time and is not asleep.
Time frame: baseline and after 64 weeks treatment
Population: Full Analysis Set (FAS 2) for open label period with observed case (OC)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole Extended Release Group (PPX ER) | Change From Baseline in Percentage On-time Without Dyskinesia (Open-label: Maintenance Phase) | 11.9 Percentage of on-time | Standard Deviation 21.1 |
Secondary
Change From Baseline in Percentage On-time Without Dyskinesia or With Non-troublesome Dyskinesia
Percentage on-time without dyskinesia or non-troublesome dyskinesia during waking hours in the last two days based on patient diary data, percentage ranging from 0 (worst case) to 100 (best case). On-time describes a period when the patient has no symptoms of off-time and is not asleep.
Time frame: baseline and after 12 weeks treatment
Population: Full Analysis Set (FAS) with last observation carried forward (LOCF)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole Extended Release Group (PPX ER) | Change From Baseline in Percentage On-time Without Dyskinesia or With Non-troublesome Dyskinesia | 6.0 Percentage of on-time | Standard Error 2.5 |
| Pramipexole Immediate Release Group (PPX IR) | Change From Baseline in Percentage On-time Without Dyskinesia or With Non-troublesome Dyskinesia | 7.1 Percentage of on-time | Standard Error 2.5 |
Secondary
Change From Baseline in Percentage On-time Without Dyskinesia or With Non-troublesome Dyskinesia (Open-label Maintenance Phase)
Percentage on-time without dyskinesia or non-troublesome dyskinesia during waking hours in the last two days based on patient diary data, percentage ranging from 0 (worst case) to 100 (best case). On-time describes a period when the patient has no symptoms of off-time and is not asleep.
Time frame: baseline and after 64 weeks treatment
Population: Full Analysis Set (FAS 2) for open label period with observed case (OC)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole Extended Release Group (PPX ER) | Change From Baseline in Percentage On-time Without Dyskinesia or With Non-troublesome Dyskinesia (Open-label Maintenance Phase) | 11.8 Percentage of on-time | Standard Deviation 21.6 |
Secondary
Change From Baseline in Percentage On-time With Troublesome Dyskinesia
Percentage on-time with troublesome dyskinesia during waking hours in the last two days based on patient diary data, percentage ranging from 0 (best case) to 100 (worst case). On-time describes a period when the patient has no symptoms of off-time and is not asleep.
Time frame: baseline and after 12 weeks treatment
Population: Full Analysis Set (FAS) with last observation carried forward (LOCF)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole Extended Release Group (PPX ER) | Change From Baseline in Percentage On-time With Troublesome Dyskinesia | -0.1 Percentage of on-time | Standard Error 0.5 |
| Pramipexole Immediate Release Group (PPX IR) | Change From Baseline in Percentage On-time With Troublesome Dyskinesia | 0.5 Percentage of on-time | Standard Error 0.5 |
Secondary
Change From Baseline in Percentage On-time With Troublesome Dyskinesia (Open-label Maintenance Phase)
Percentage on-time with troublesome dyskinesia during waking hours in the last two days based on patient diary data, percentage ranging from 0 (best case) to 100 (worst case). On-time describes a period when the patient has no symptoms of off-time and is not asleep.
Time frame: baseline and after 64 weeks treatment
Population: Full Analysis Set (FAS 2) for open label period with observed case (OC)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole Extended Release Group (PPX ER) | Change From Baseline in Percentage On-time With Troublesome Dyskinesia (Open-label Maintenance Phase) | -0.2 Percentage of on-time | Standard Deviation 2.8 |
Secondary
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Parts II+III Total Score
UPDRS II+III ranging from 0 point(normal) to 160 point (severe). UPDRS part II measures activities of daily living, part III measures motor symptoms
Time frame: baseline and after 12 weeks treatment
Population: Full Analysis Set (FAS) with last observation carried forward (LOCF)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole Extended Release Group (PPX ER) | Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Parts II+III Total Score | -13.6 UPDRS scores on a scale | Standard Error 1.3 |
| Pramipexole Immediate Release Group (PPX IR) | Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Parts II+III Total Score | -13.3 UPDRS scores on a scale | Standard Error 1.3 |
Secondary
Change From Baseline in UPDRS Part III Score
UPDRS Part III ranging from 0 (normal) to 108 (severe). UPDRS Part III measures motor symptoms
Time frame: baseline and after 12 weeks treatment
Population: Full Analysis Set (FAS) with last observation carried forward (LOCF)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole Extended Release Group (PPX ER) | Change From Baseline in UPDRS Part III Score | -10.2 UPDRS scores on a scale | Standard Error 1 |
| Pramipexole Immediate Release Group (PPX IR) | Change From Baseline in UPDRS Part III Score | -9.9 UPDRS scores on a scale | Standard Error 1 |
Secondary
Change From Baseline in UPDRS Part III Score (Open-label: Maintenance Phase)
UPDRS Part III ranging from 0 (normal) to 108 (severe). UPDRS Part III measures motor symptoms
Time frame: baseline and after 64 weeks treatment
Population: Full Analysis Set (FAS 2) for open label period with observed case (OC)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole Extended Release Group (PPX ER) | Change From Baseline in UPDRS Part III Score (Open-label: Maintenance Phase) | -11.9 UPDRS scores on a scale | Standard Error 8.2 |
Secondary
Change From Baseline in UPDRS Part II Score
UPDRS Part II ranging from 0 (normal) to 52 (severe). UPDRS Part II is calculated as the average of UPDRS Part II at on and UPDRS Part II at off-period for each of the 13 activities.
Time frame: baseline and after 12 weeks treatment
Population: Full Analysis Set (FAS) with last observation carried forward (LOCF)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole Extended Release Group (PPX ER) | Change From Baseline in UPDRS Part II Score | -3.3 UPDRS scores on a scale | Standard Error 0.4 |
| Pramipexole Immediate Release Group (PPX IR) | Change From Baseline in UPDRS Part II Score | -3.4 UPDRS scores on a scale | Standard Error 0.4 |
Secondary
Change From Baseline in UPDRS Part II Score (Open-label: Maintenance Phase)
UPDRS Part II ranging from 0 (normal) to 52 (severe). UPDRS Part II is calculated as the average of UPDRS Part II at on and UPDRS Part II at off-period for each of the 13 activities.
Time frame: baseline and after 64 weeks treatment
Population: Full Analysis Set (FAS 2) for open label period with observed case (OC)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole Extended Release Group (PPX ER) | Change From Baseline in UPDRS Part II Score (Open-label: Maintenance Phase) | -3.4 UPDRS scores on a scale | Standard Deviation 4.2 |
Secondary
Change From Baseline in UPDRS Part I Score
UPDRS Part I ranging from 0 (normal) to 16 (severe). UPDRS Part I measures Mentation, Behavior and Mood
Time frame: baseline and after 12 weeks treatment
Population: Full Analysis Set (FAS) with last observation carried forward (LOCF)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole Extended Release Group (PPX ER) | Change From Baseline in UPDRS Part I Score | 0.1 UPDRS scores on a scale | Standard Error 0.2 |
| Pramipexole Immediate Release Group (PPX IR) | Change From Baseline in UPDRS Part I Score | -0.2 UPDRS scores on a scale | Standard Error 0.2 |
Secondary
Change From Baseline in UPDRS Part I Score (Open-label: Maintenance Phase)
UPDRS Part I ranging from 0 (normal) to 16 (severe). UPDRS Part I measures Mentation, Behavior and Mood
Time frame: baseline and after 64 weeks treatment
Population: Full Analysis Set (FAS 2) for open label period with observed case (OC)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole Extended Release Group (PPX ER) | Change From Baseline in UPDRS Part I Score (Open-label: Maintenance Phase) | -0.3 UPDRS scores on a scale | Standard Deviation 1.5 |
Secondary
Change From Baseline in UPDRS Part IV Score
UPDRS Part IV ranging from 0 (normal) to 23 (severe). UPDRS Part IV measures complications of therapy
Time frame: baseline and after 12 weeks treatment
Population: Full Analysis Set (FAS) with last observation carried forward (LOCF)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole Extended Release Group (PPX ER) | Change From Baseline in UPDRS Part IV Score | -0.2 UPDRS scores on a scale | Standard Error 0.2 |
| Pramipexole Immediate Release Group (PPX IR) | Change From Baseline in UPDRS Part IV Score | -0.4 UPDRS scores on a scale | Standard Error 0.2 |
Secondary
Change From Baseline in UPDRS Part IV Score (Open-label: Maintenance Phase)
UPDRS Part IV ranging from 0 (normal) to 23 (severe). UPDRS Part IV measures complications of therapy
Time frame: baseline and after 64 weeks treatment
Population: Full Analysis Set (FAS 2) for open label period with observed case (OC)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole Extended Release Group (PPX ER) | Change From Baseline in UPDRS Part IV Score (Open-label: Maintenance Phase) | -0.6 UPDRS scores on a scale | Standard Deviation 1.6 |
Secondary
Change From Baseline in UPDRS (Unified Parkinson's Disease Rating Scale) Parts II+III Total Score (Open-label: Maintenance Phase)
UPDRS II+III ranging from 0 point(normal) to 160 point (severe). UPDRS part II measures activities of daily living, part III measures motor symptoms
Time frame: Baseline and after 64 weeks treatment
Population: Full Analysis Set (FAS 2) for open label period with observed case (OC)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole Extended Release Group (PPX ER) | Change From Baseline in UPDRS (Unified Parkinson's Disease Rating Scale) Parts II+III Total Score (Open-label: Maintenance Phase) | -15.2 UPDRS scores on a scale | Standard Deviation 11.1 |
Secondary
Change From End of Double-Blind Period in UPDRS (Unified Parkinson's Disease Rating Scale) Parts II+III Total Score (Open-label: Dose Adjustment Phase)
UPDRS II+III ranging from 0 point(normal) to 160 point (severe). UPDRS part II measures activities of daily living, part III measures motor symptoms. Least square means and standard errors presented are from ANCOVA with factors treatment and covariate baseline.
Time frame: Week 12 to Week 16
Population: Full Analysis Set (FAS 2) for open label period with observed case (OC)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole Extended Release Group (PPX ER) | Change From End of Double-Blind Period in UPDRS (Unified Parkinson's Disease Rating Scale) Parts II+III Total Score (Open-label: Dose Adjustment Phase) | -2.2 UPDRS scores on a scale | Standard Error 0.6 |
| Pramipexole Immediate Release Group (PPX IR) | Change From End of Double-Blind Period in UPDRS (Unified Parkinson's Disease Rating Scale) Parts II+III Total Score (Open-label: Dose Adjustment Phase) | -0.2 UPDRS scores on a scale | Standard Error 0.6 |
Secondary
Clinical Global Impression of Improvement (CGI-I) at Week 16 Compared to Patient's CGI-I Status at Week 12 (Open-label: Dose Adjustment Phase)
Clinical Global Impression of Improvement (CGI-I) at week 16 compared to patient's CGI-I status at week 12. CGI-I scores ranging from '1' (very much improved) to '7' (very much worse)
Time frame: Week 12 to Week 16
Population: Full Analysis Set (FAS 2) for open label period with observed case (OC)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pramipexole Extended Release Group (PPX ER) | Clinical Global Impression of Improvement (CGI-I) at Week 16 Compared to Patient's CGI-I Status at Week 12 (Open-label: Dose Adjustment Phase) | Much improved | 8.0 percentage of participants |
| Pramipexole Extended Release Group (PPX ER) | Clinical Global Impression of Improvement (CGI-I) at Week 16 Compared to Patient's CGI-I Status at Week 12 (Open-label: Dose Adjustment Phase) | No change | 34.0 percentage of participants |
| Pramipexole Extended Release Group (PPX ER) | Clinical Global Impression of Improvement (CGI-I) at Week 16 Compared to Patient's CGI-I Status at Week 12 (Open-label: Dose Adjustment Phase) | Very much improved | 0.0 percentage of participants |
| Pramipexole Extended Release Group (PPX ER) | Clinical Global Impression of Improvement (CGI-I) at Week 16 Compared to Patient's CGI-I Status at Week 12 (Open-label: Dose Adjustment Phase) | Minimally worse | 10.0 percentage of participants |
| Pramipexole Extended Release Group (PPX ER) | Clinical Global Impression of Improvement (CGI-I) at Week 16 Compared to Patient's CGI-I Status at Week 12 (Open-label: Dose Adjustment Phase) | Minimally improved | 48.0 percentage of participants |
| Pramipexole Immediate Release Group (PPX IR) | Clinical Global Impression of Improvement (CGI-I) at Week 16 Compared to Patient's CGI-I Status at Week 12 (Open-label: Dose Adjustment Phase) | Minimally worse | 5.7 percentage of participants |
| Pramipexole Immediate Release Group (PPX IR) | Clinical Global Impression of Improvement (CGI-I) at Week 16 Compared to Patient's CGI-I Status at Week 12 (Open-label: Dose Adjustment Phase) | Much improved | 5.7 percentage of participants |
| Pramipexole Immediate Release Group (PPX IR) | Clinical Global Impression of Improvement (CGI-I) at Week 16 Compared to Patient's CGI-I Status at Week 12 (Open-label: Dose Adjustment Phase) | Minimally improved | 35.8 percentage of participants |
| Pramipexole Immediate Release Group (PPX IR) | Clinical Global Impression of Improvement (CGI-I) at Week 16 Compared to Patient's CGI-I Status at Week 12 (Open-label: Dose Adjustment Phase) | No change | 50.9 percentage of participants |
| Pramipexole Immediate Release Group (PPX IR) | Clinical Global Impression of Improvement (CGI-I) at Week 16 Compared to Patient's CGI-I Status at Week 12 (Open-label: Dose Adjustment Phase) | Very much improved | 1.9 percentage of participants |
Secondary
Dose Proportionality of Trough Plasma Concentration at Steady State After Pramipexole ER Treatment
Dose proportionality of trough plasma concentrations at steady state is explored by using the power model that described the functional relationship between the dose and plasma concentration
Time frame: from Visit 1 to Visit 8 after pramipexole ER
Population: Full Analysis Set (FAS).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole Extended Release Group (PPX ER) | Dose Proportionality of Trough Plasma Concentration at Steady State After Pramipexole ER Treatment | 1.0375 ng/mL | Standard Error 0.0177 |
Secondary
Patient Global Impression of Improvement (PGI-I) at Week 16 Compared to Patient's PGI-I Status at Week 12 (Open-label: Dose Adjustment Phase)
Patient Global Impression of Improvement (PGI-I) at week 16 compared to patient's PGI-I status at week 12. PGI-I scores ranging from '1' (very much better) to '7' (very much worse).
Time frame: Week 12 to Week 16
Population: Full Analysis Set (FAS 2) for open label period with observed case (OC)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pramipexole Extended Release Group (PPX ER) | Patient Global Impression of Improvement (PGI-I) at Week 16 Compared to Patient's PGI-I Status at Week 12 (Open-label: Dose Adjustment Phase) | Much better | 14.0 percentage of participants |
| Pramipexole Extended Release Group (PPX ER) | Patient Global Impression of Improvement (PGI-I) at Week 16 Compared to Patient's PGI-I Status at Week 12 (Open-label: Dose Adjustment Phase) | No change | 36.0 percentage of participants |
| Pramipexole Extended Release Group (PPX ER) | Patient Global Impression of Improvement (PGI-I) at Week 16 Compared to Patient's PGI-I Status at Week 12 (Open-label: Dose Adjustment Phase) | A little better | 36.0 percentage of participants |
| Pramipexole Extended Release Group (PPX ER) | Patient Global Impression of Improvement (PGI-I) at Week 16 Compared to Patient's PGI-I Status at Week 12 (Open-label: Dose Adjustment Phase) | A little worse | 12.0 percentage of participants |
| Pramipexole Extended Release Group (PPX ER) | Patient Global Impression of Improvement (PGI-I) at Week 16 Compared to Patient's PGI-I Status at Week 12 (Open-label: Dose Adjustment Phase) | Very much better | 2.0 percentage of participants |
| Pramipexole Immediate Release Group (PPX IR) | Patient Global Impression of Improvement (PGI-I) at Week 16 Compared to Patient's PGI-I Status at Week 12 (Open-label: Dose Adjustment Phase) | A little worse | 9.4 percentage of participants |
| Pramipexole Immediate Release Group (PPX IR) | Patient Global Impression of Improvement (PGI-I) at Week 16 Compared to Patient's PGI-I Status at Week 12 (Open-label: Dose Adjustment Phase) | Very much better | 3.8 percentage of participants |
| Pramipexole Immediate Release Group (PPX IR) | Patient Global Impression of Improvement (PGI-I) at Week 16 Compared to Patient's PGI-I Status at Week 12 (Open-label: Dose Adjustment Phase) | Much better | 11.3 percentage of participants |
| Pramipexole Immediate Release Group (PPX IR) | Patient Global Impression of Improvement (PGI-I) at Week 16 Compared to Patient's PGI-I Status at Week 12 (Open-label: Dose Adjustment Phase) | A little better | 35.8 percentage of participants |
| Pramipexole Immediate Release Group (PPX IR) | Patient Global Impression of Improvement (PGI-I) at Week 16 Compared to Patient's PGI-I Status at Week 12 (Open-label: Dose Adjustment Phase) | No change | 39.6 percentage of participants |
Secondary
Percentage of Patients With no Worsening of UPDRS Parts II+III Total Score by More Than 15% From Week 12 to Week 16 (Open-label: Dose Adjustment Phase)
Percentage of patients with no worsening of UPDRS Parts II+III Total Score by more than 15% from week 12 to week 16 (Open-label: Dose Adjustment Phase)
Time frame: Week 12 to Week 16
Population: Full Analysis Set (FAS 2) for the open-label period
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pramipexole Extended Release Group (PPX ER) | Percentage of Patients With no Worsening of UPDRS Parts II+III Total Score by More Than 15% From Week 12 to Week 16 (Open-label: Dose Adjustment Phase) | 78.4 percentage of participants |
| Pramipexole Immediate Release Group (PPX IR) | Percentage of Patients With no Worsening of UPDRS Parts II+III Total Score by More Than 15% From Week 12 to Week 16 (Open-label: Dose Adjustment Phase) | 83.0 percentage of participants |
Secondary
Responder Rate For Clinical Global Impression of Improvement (CGI-I)
CGI-I scores ranging from '1' (very much improved) to '7' (very much worse), CGI-I responder have scoring of 1 or 2 (at least much improved)
Time frame: baseline and after 12 weeks treatment
Population: Full Analysis Set (FAS) with last observation carried forward (LOCF)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pramipexole Extended Release Group (PPX ER) | Responder Rate For Clinical Global Impression of Improvement (CGI-I) | 48.2 percentage of participants |
| Pramipexole Immediate Release Group (PPX IR) | Responder Rate For Clinical Global Impression of Improvement (CGI-I) | 50.0 percentage of participants |
Secondary
Responder Rate For Patient Global Impression of Improvement (PGI-I)
PGI-I scores ranging from '1' (very much better) to '7' (very much worse), PGI-I responder have scoring of 1 or 2 (at least much better)
Time frame: baseline and after 12 weeks treatment
Population: Full Analysis Set (FAS) with last observation carried forward (LOCF)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pramipexole Extended Release Group (PPX ER) | Responder Rate For Patient Global Impression of Improvement (PGI-I) | 33.9 percentage of participants |
| Pramipexole Immediate Release Group (PPX IR) | Responder Rate For Patient Global Impression of Improvement (PGI-I) | 33.9 percentage of participants |
Secondary
Trough Plasma Concentration at Steady State
Geometric mean (gMean) was calculated for trough plasma concentrations of pramipexole at steady state after administration of pramipexole IR 4.5mg and pramipexole ER 4.5mg.
Time frame: at Visit 8 after pramipexole ER 4.5mg and IR 4.5mg treatment
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole Extended Release Group (PPX ER) | Trough Plasma Concentration at Steady State | 5.46 ng/ml | Standard Deviation 2.01 |
| Pramipexole Immediate Release Group (PPX IR) | Trough Plasma Concentration at Steady State | 5.09 ng/ml | Standard Deviation 2.53 |
Secondary
UPDRS Parts II+III Total Score Responder Rate (at Least 20% Improvement)
Responders are defined as at least 20% decrease in the UPDRS Parts II+III Total Score ranges 0-160 scores from best to worse
Time frame: baseline and after 12 weeks treatment
Population: Full Analysis Set (FAS) with last observation carried forward (LOCF)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pramipexole Extended Release Group (PPX ER) | UPDRS Parts II+III Total Score Responder Rate (at Least 20% Improvement) | 78.6 percentage of participants |
| Pramipexole Immediate Release Group (PPX IR) | UPDRS Parts II+III Total Score Responder Rate (at Least 20% Improvement) | 82.1 percentage of participants |
Secondary
UPDRS Parts II+III Total Score Responder Rate (at Least 20% Improvement) (Open-label: Maintenance Phase)
Responders are defined as at least 20% decrease in the UPDRS Parts II+III Total Score ranges 0-160 scores from best to worse
Time frame: baseline and after 64 weeks treatment
Population: Full Analysis Set (FAS 2) for open label period with observed case (OC)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pramipexole Extended Release Group (PPX ER) | UPDRS Parts II+III Total Score Responder Rate (at Least 20% Improvement) (Open-label: Maintenance Phase) | 92.0 percentage of participants |