Trial Outcomes & Findings for Pramipexole Extended Release Versus Pramipexole Immediate Release for 18 Weeks in Chinese Parkinson's Disease (PD) Patients (NCT NCT01191944)

NCT ID: NCT01191944

Last Updated: 2014-10-31

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 475 participants
• Primary outcome timeframe: Baseline and week 18
• Results posted on: 2014-10-31

Participant Flow

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.

Participant milestones

Measure	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	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
Overall Study STARTED	234	239
Overall Study COMPLETED	217	220
Overall Study NOT COMPLETED	17	19

Reasons for withdrawal

Measure	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	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
Overall Study Adverse Event	11	12
Overall Study Protocol Violation	1	2
Overall Study Withdrawal by Subject	4	2
Overall Study Other	1	3

Baseline Characteristics

Pramipexole Extended Release Versus Pramipexole Immediate Release for 18 Weeks in Chinese Parkinson's Disease (PD) Patients

Baseline characteristics by cohort

Measure	Pramipexole ER n=234 Participants 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	Pramipexole IR n=239 Participants 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	Total n=473 Participants Total of all reporting groups
Age, Continuous	62.2 years STANDARD_DEVIATION 9.10 • n=5 Participants	61.8 years STANDARD_DEVIATION 9.03 • n=7 Participants	62.0 years STANDARD_DEVIATION 9.06 • n=5 Participants
Sex: Female, Male Female	80 Participants n=5 Participants	95 Participants n=7 Participants	175 Participants n=5 Participants
Sex: Female, Male Male	154 Participants n=5 Participants	144 Participants n=7 Participants	298 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Pramipexole IR n=236 Participants 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	Pramipexole ER n=228 Participants 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
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	-13.807 Units on a scale Standard Error 0.6547

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Pramipexole IR n=106 Participants 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	Pramipexole ER n=110 Participants 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
Change From Baseline in Percentage Off-time During Waking Hours at Week 18	-7.443 Percentage off-time Standard Error 1.5362	-6.962 Percentage off-time Standard Error 1.5072

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Pramipexole IR n=106 Participants 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	Pramipexole ER n=110 Participants 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
Change From Baseline in Duration of Off-time During Waking Hours at Week 18	-1.098 hours Standard Error 0.2300	-1.044 hours Standard Error 0.2256

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Pramipexole IR n=106 Participants 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	Pramipexole ER n=110 Participants 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
Responder in Percentage Off-time During Waking Hours at Week 18 Responder	59 Participants	58 Participants
Responder in Percentage Off-time During Waking Hours at Week 18 Non-Responder	47 Participants	52 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Pramipexole IR n=106 Participants 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	Pramipexole ER n=110 Participants 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
Change From Baseline in Percentage On-time Without Dyskinesia at Week 18	4.265 Percentage of on-time Standard Error 1.9643	7.028 Percentage of on-time Standard Error 1.9274

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Pramipexole IR n=106 Participants 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	Pramipexole ER n=110 Participants 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
Change From Baseline in Percentage On-time With Non-troublesome Dyskinesia at Week 18	3.275 Percentage of on-time Standard Error 1.1013	-0.235 Percentage of on-time Standard Error 1.0807

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Pramipexole IR n=106 Participants 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	Pramipexole ER n=110 Participants 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
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	6.855 Percentage of on-time Standard Error 1.5672

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Pramipexole IR n=106 Participants 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	Pramipexole ER n=110 Participants 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
Change From Baseline in Percentage On-time With Troublesome Dyskinesia at Week 18	0.226 Percentage of on-time Standard Error 0.3463	-0.142 Percentage of on-time Standard Error 0.3398

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Pramipexole IR n=106 Participants 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	Pramipexole ER n=110 Participants 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
Change From Baseline in Duration of On-time Without Dyskinesia at Week 18	0.496 hours Standard Error 0.3134	1.026 hours Standard Error 0.3076

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Pramipexole IR n=106 Participants 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	Pramipexole ER n=110 Participants 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
Change From Baseline in Duration of On-time With Non-troublesome Dyskinesia at Week 18	0.518 hours Standard Error 0.1773	-0.044 hours Standard Error 0.1740

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Pramipexole IR n=106 Participants 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	Pramipexole ER n=110 Participants 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
Change From Baseline in Duration of On-time Without or With Non-troublesome Dyskinesia at Week 18	1.013 hours Standard Error 0.2632	0.982 hours Standard Error 0.2583

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Pramipexole IR n=106 Participants 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	Pramipexole ER n=110 Participants 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
Change From Baseline in Duration of On-time With Troublesome Dyskinesia at Week 18	0.031 hours Standard Error 0.0564	-0.000 hours Standard Error 0.0553

SECONDARY outcome

Timeframe: 18 weeks

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

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.

Outcome measures

Measure	Pramipexole IR n=233 Participants 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	Pramipexole ER n=224 Participants 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
Clinical Global Impression of Improvement (CGI-I) Responder at Week 18 Non-Responder	95 Participants	99 Participants
Clinical Global Impression of Improvement (CGI-I) Responder at Week 18 Responder	138 Participants	125 Participants

SECONDARY outcome

Timeframe: 18 weeks

Population: FAS (LOCF)

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.

Outcome measures

Measure	Pramipexole IR n=236 Participants 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	Pramipexole ER n=228 Participants 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
Patient Global Impressions of Improvement (PGI-I) Responder at Week 18 Responder	127 Participants	119 Participants
Patient Global Impressions of Improvement (PGI-I) Responder at Week 18 Non-Responder	109 Participants	109 Participants

SECONDARY outcome

Timeframe: Baseline and week 18

Population: FAS (LOCF)

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).

Outcome measures

Measure	Pramipexole IR n=236 Participants 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	Pramipexole ER n=228 Participants 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
Responder in UPDRS Parts II+III Score at Week 18 Responder	154 Participants	164 Participants
Responder in UPDRS Parts II+III Score at Week 18 Non-Responder	82 Participants	64 Participants

SECONDARY outcome

Timeframe: Baseline and week 18

Population: FAS (LOCF)

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.

Outcome measures

Measure	Pramipexole IR n=236 Participants 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	Pramipexole ER n=228 Participants 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
Change From Baseline in UPDRS II Score Separately at Week 18	-3.596 Units on a scale Standard Error 0.2197	-3.750 Units on a scale Standard Error 0.2235

SECONDARY outcome

Timeframe: Baseline and week 18

Population: FAS (LOCF)

UPDRS Part III (motor examination) ranges from 0 to 108. Reduction over time represents an improvement. Means are adjusted for treatment, centre and baseline.

Outcome measures

Measure	Pramipexole IR n=236 Participants 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	Pramipexole ER n=228 Participants 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
Change From Baseline in UPDRS III Score Separately at Week 18	-9.440 Units on a scale Standard Error 0.4962	-10.068 Units on a scale Standard Error 0.5048

SECONDARY outcome

Timeframe: 18 weeks

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

Number of patients without concomitant L-Dopa treatment at baseline which required L-Dopa supplementation during the study.

Outcome measures

Measure	Pramipexole IR n=40 Participants 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	Pramipexole ER n=25 Participants 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
Levodopa (L-Dopa) Introduction During the Study with L-Dopa introduction	0 Participants	1 Participants
Levodopa (L-Dopa) Introduction During the Study without L-Dopa introduction	40 Participants	24 Participants

SECONDARY outcome

Timeframe: 18 weeks

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

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.

Outcome measures

Measure	Pramipexole IR n=196 Participants 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	Pramipexole ER n=203 Participants 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
Levodopa (L-Dopa) Dose Change During the Study	-11.22 mg Standard Deviation 101.913	-5.17 mg Standard Deviation 51.563

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and week 18

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

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).

Outcome measures

Measure	Pramipexole IR n=215 Participants 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	Pramipexole ER n=217 Participants 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
Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score at 18 Weeks	-0.0 Units on a scale Standard Deviation 3.38	0.1 Units on a scale Standard Deviation 3.43

Adverse Events

Pramipexole ER

Serious events: 6 serious events

Other events: 93 other events

Deaths: 0 deaths

Pramipexole IR

Serious events: 13 serious events

Other events: 90 other events

Deaths: 0 deaths

Serious adverse events

Measure	Pramipexole ER n=234 participants at risk 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	Pramipexole IR n=239 participants at risk 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
Cardiac disorders Acute coronary syndrome	0.43% 1/234 • Up to 18 weeks	0.42% 1/239 • Up to 18 weeks
Cardiac disorders Angina pectoris	0.00% 0/234 • Up to 18 weeks	0.42% 1/239 • Up to 18 weeks
Cardiac disorders Cardiac failure chronic	0.43% 1/234 • Up to 18 weeks	0.00% 0/239 • Up to 18 weeks
Cardiac disorders Cor pulmonale	0.43% 1/234 • Up to 18 weeks	0.00% 0/239 • Up to 18 weeks
Eye disorders Vision blurred	0.00% 0/234 • Up to 18 weeks	0.42% 1/239 • Up to 18 weeks
Infections and infestations Bronchitis	0.00% 0/234 • Up to 18 weeks	0.42% 1/239 • Up to 18 weeks
Infections and infestations Lung infection	0.00% 0/234 • Up to 18 weeks	0.42% 1/239 • Up to 18 weeks
Infections and infestations Pneumonia	0.00% 0/234 • Up to 18 weeks	0.42% 1/239 • Up to 18 weeks
Infections and infestations Upper respiratory tract infection	0.00% 0/234 • Up to 18 weeks	0.42% 1/239 • Up to 18 weeks
Injury, poisoning and procedural complications Face injury	0.00% 0/234 • Up to 18 weeks	0.42% 1/239 • Up to 18 weeks
Injury, poisoning and procedural complications Femur fracture	0.00% 0/234 • Up to 18 weeks	0.84% 2/239 • Up to 18 weeks
Injury, poisoning and procedural complications Fracture	0.43% 1/234 • Up to 18 weeks	0.00% 0/239 • Up to 18 weeks
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/234 • Up to 18 weeks	0.84% 2/239 • Up to 18 weeks
Injury, poisoning and procedural complications Joint dislocation	0.00% 0/234 • Up to 18 weeks	0.42% 1/239 • Up to 18 weeks
Nervous system disorders Cerebral infarction	0.43% 1/234 • Up to 18 weeks	0.00% 0/239 • Up to 18 weeks
Nervous system disorders Parkinson's disease	0.00% 0/234 • Up to 18 weeks	0.42% 1/239 • Up to 18 weeks
Nervous system disorders Transient ischaemic attack	0.43% 1/234 • Up to 18 weeks	0.00% 0/239 • Up to 18 weeks
Reproductive system and breast disorders Uterine polyp	0.43% 1/234 • Up to 18 weeks	0.00% 0/239 • Up to 18 weeks
Vascular disorders Orthostatic hypotension	0.00% 0/234 • Up to 18 weeks	0.42% 1/239 • Up to 18 weeks

Other adverse events

Measure	Pramipexole ER n=234 participants at risk 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	Pramipexole IR n=239 participants at risk 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
Gastrointestinal disorders Constipation	7.3% 17/234 • Up to 18 weeks	8.4% 20/239 • Up to 18 weeks
Gastrointestinal disorders Nausea	8.5% 20/234 • Up to 18 weeks	7.1% 17/239 • Up to 18 weeks
Nervous system disorders Dizziness	12.8% 30/234 • Up to 18 weeks	13.0% 31/239 • Up to 18 weeks
Nervous system disorders Dyskinesia	5.1% 12/234 • Up to 18 weeks	7.5% 18/239 • Up to 18 weeks
Nervous system disorders Somnolence	21.8% 51/234 • Up to 18 weeks	14.6% 35/239 • Up to 18 weeks

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: clintriage.rdg@boehringer-ingelheim.com

Results disclosure agreements

• Principal investigator is a sponsor employee Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
• Publication restrictions are in place

Restriction type: OTHER