Pramipexole Extended Release Versus Pramipexole Immediate... | NCT01191944

Status Module

Label	Type	Description	Intervention Names
pramipexole Extended release	Experimental	subjects will receive 0.375mg once a day to 4.5mg once a day depending on investigator's judgement	Drug: pramipexole extended release tablet
pramipexole Immediate release	Active Comparator	subjects will receive 0.125mg three times a day to 1.0mg three times a day depending on investigator's judgement	Drug: pramipexole immediate release tablet

Name	Type	Description	Arm Group Labels	Other Names
pramipexole immediate release tablet	Drug	0.375mg-4.5mg(daily dose), three times a day	pramipexole Immediate release

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	Baseline and week 18

Secondary Outcomes

Measure	Description	Time Frame
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.

Other Outcomes

Measure	Description	Time Frame
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).

Eligibility Module

Eligibility Criteria

Inclusion criteria:

Male or female Chinese patient with idiopathic Parkinson's disease (PD) confirmed by at least two of the following signs: resting tremor, bradykinesia, rigidity.
Parkinson's disease diagnosed for at least 2 years.
Patients 30 years of age or older at the time of diagnosis.
Modified Hoehn and Yahr stage of 2 to 4 at on-time.
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.
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).
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).
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:

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).
Dementia, as defined by a Mini-Mental State Exam score < 24 at screening visit [R96-2656].
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.
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).
History of deep brain stimulation
Clinically significant electrocardiogram abnormalities at screening visit, according to investigator's judgement.
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.
Malignant melanoma or history of previously treated malignant melanoma.
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.
Pregnancy (to be excluded by urine pregnancy test at screening visit) or breast-feeding.
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).
Serum levels of Aspartate Aminotransferase, Alanine Aminotransferase , alkaline phosphatases or total bilirubin > 2 Upper Limit of Normal (on screening lab test).
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)

Name	Affiliation	Role
Boehringer Ingelheim	Boehringer Ingelheim	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
248.671.86004 Boehringer Ingelheim Investigational Site		Beijing			China
248.671.86006 Boehringer Ingelheim Investigational Site

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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
FG001	Pramipexole IR

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

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.

Posted

Least Squares Mean

Standard Error

Units on a scale

Baseline and week 18

ID	Title	Description
OG000	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
OG001	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

Units	Counts
Participants	OG000228 OG001236

Title

Denominators

Categories

Title	Measurements
	OG000-13.807± 0.6547 OG001-13.047± 0.6434

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	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.	ANCOVA	adjusted for treatment, centre and baseline	<0.0001	one-sided test relative to NI margin of -4	Mean Difference (Final Values)	0.760	Standard Error of the Mean	0.9192		95	-1.047	2.566			Pramipexole IR minus Pramipexole ER, Pramipexole ER non inferior to Pramipexole IR if lower limit of confidence interval (CI) for the mean difference is higher than NI margin.

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.

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.

Posted

Least Squares Mean

Standard Error

Percentage off-time

Baseline and week 18

ID	Title	Description
OG000	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
OG001	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

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.

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.

Posted

Least Squares Mean

Standard Error

hours

Baseline and week 18

ID	Title	Description
OG000	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
OG001	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

Units	Counts

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.

Posted

Number

Participants

Baseline and week 18

ID	Title	Description
OG000	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
OG001	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

Units	Counts

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.

Posted

Least Squares Mean

Standard Error

Percentage of on-time

Baseline and week 18

ID	Title	Description
OG000	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
OG001	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

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.

Posted

Least Squares Mean

Standard Error

Percentage of on-time

Baseline and week 18

ID	Title	Description
OG000	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
OG001	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

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.

Posted

Least Squares Mean

Standard Error

Percentage of on-time

Baseline and week 18

ID	Title	Description
OG000	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
OG001	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

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.

Posted

Least Squares Mean

Standard Error

Percentage of on-time

Baseline and week 18

ID	Title	Description
OG000	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
OG001	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

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.

Posted

Least Squares Mean

Standard Error

hours

Baseline and week 18

ID	Title	Description
OG000	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
OG001	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

Units	Counts

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.

Posted

Least Squares Mean

Standard Error

hours

Baseline and week 18

ID	Title	Description
OG000	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
OG001	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

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.

Posted

Least Squares Mean

Standard Error

hours

Baseline and week 18

ID	Title	Description
OG000	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
OG001	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

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.

Posted

Least Squares Mean

Standard Error

hours

Baseline and week 18

ID	Title	Description
OG000	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
OG001	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

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.

FAS (LOCF). Only patients with on-treatment CGI-I evaluation were analyzed.

Posted

Number

Participants

18 weeks

ID	Title	Description
OG000	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
OG001	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

Units	Counts
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.

FAS (LOCF)

Posted

Number

Participants

18 weeks

ID	Title	Description
OG000	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
OG001	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

Units	Counts
Participants

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).

FAS (LOCF)

Posted

Number

Participants

Baseline and week 18

ID	Title	Description
OG000	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
OG001	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

Units	Counts
Participants	OG000

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.

FAS (LOCF)

Posted

Least Squares Mean

Standard Error

Units on a scale

Baseline and week 18

ID	Title	Description
OG000	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
OG001	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

Units	Counts
Participants	OG000

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).

Observed cases (OC). Only patients with ESS assessment at baseline and at 18 weeks were analyzed.

Posted

Mean

Standard Deviation

Units on a scale

Baseline and week 18

ID	Title	Description
OG000	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
OG001	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

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.

FAS (LOCF)

Posted

Least Squares Mean

Standard Error

Units on a scale

Baseline and week 18

ID	Title	Description
OG000	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
OG001	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

Units	Counts
Participants	OG000

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.

FAS. Only patients without concomitant L-Dopa treatment at baseline.

Posted

Number

Participants

18 weeks

ID	Title	Description
OG000	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
OG001	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

Units	Counts
Participants	OG000

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.

FAS. Only patients with concomitant L-Dopa treatment at baseline.

Posted

Mean

Standard Deviation

18 weeks

ID	Title	Description
OG000	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
OG001	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

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute coronary syndrome	Cardiac disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected234 at risk EG0011 affected239 at risk
Angina pectoris	Cardiac disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected234 at risk EG0011 affected239 at risk
Cardiac failure chronic	Cardiac disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected234 at risk EG0010 affected239 at risk
Cor pulmonale	Cardiac disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected234 at risk EG0010 affected239 at risk
Vision blurred	Eye disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected234 at risk EG0011 affected239 at risk
Bronchitis	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0000 affected234 at risk EG0011 affected239 at risk
Lung infection	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0000 affected234 at risk EG0011 affected239 at risk
Pneumonia	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0000 affected234 at risk EG0011 affected239 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0000 affected234 at risk EG0011 affected239 at risk
Face injury	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0000 affected234 at risk EG0011 affected239 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0000 affected234 at risk EG0012 affected239 at risk
Fracture	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0001 affected234 at risk EG0010 affected239 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0000 affected234 at risk EG0012 affected239 at risk
Joint dislocation	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0000 affected234 at risk EG0011 affected239 at risk
Cerebral infarction	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected234 at risk EG0010 affected239 at risk
Parkinson's disease	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected234 at risk EG0011 affected239 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected234 at risk EG0010 affected239 at risk
Uterine polyp	Reproductive system and breast disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected234 at risk EG0010 affected239 at risk
Orthostatic hypotension	Vascular disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected234 at risk EG0011 affected239 at risk

ID	Term
D020734	Parkinsonian Disorders
D001480	Basal Ganglia Diseases
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D009069	Movement Disorders
D000080874	Synucleinopathies
D019636	Neurodegenerative Diseases

ID	Term
D052160	Benzothiazoles
D013844	Thiazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring

ID	Title	Description
BG000	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
BG001	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
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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			6	234	93	234
EG001	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			13	239	90	239

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Constipation	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG00017 affected234 at risk EG00120 affected239 at risk
Nausea	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG00020 affected234 at risk EG00117 affected239 at risk
Dizziness	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG00030 affected234 at risk EG00131 affected239 at risk
Dyskinesia	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG00012 affected234 at risk EG00118 affected239 at risk
Somnolence	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG00051 affected234 at risk EG00135 affected239 at risk