Trial Outcomes & Findings for Pramipexole Pilot Phase II Study in Children and Adolescents With Tourette Disorder According to DSM-IV Criteria (NCT NCT00558467)

NCT ID: NCT00558467

Last Updated: 2014-05-16

Results Overview

Total Tic Score is the sum of ten individual ratings of the impairment due to tics. Each scale ranges from 0 (None/Absent) to 5 (Severe) and total score ranges from 0 to 50. Analysis was adjusted for baseline total tic score and age as linear covariates.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 63 participants
• Primary outcome timeframe: baseline 6 weeks
• Results posted on: 2014-05-16

Participant Flow

Participant milestones

Measure	Placebo Placebo tablets matching the Pramipexole tablets to be taken per os	Pramipexole Pramipexole (tablets of 0.0625 mg, 0.125 mg and 0.25 mg) to be taken per os. Starting dose 0.0625 mg bid, with possible down titration after one week to 0.0625 mg qd or optional up titration to 0.125 mg bid, after the second week optional up titration to 0.125 mg tid, after the third week optional up titration to 0.25 mg bid.
Overall Study STARTED	20	43
Overall Study COMPLETED	19	39
Overall Study NOT COMPLETED	1	4

Reasons for withdrawal

Measure	Placebo Placebo tablets matching the Pramipexole tablets to be taken per os	Pramipexole Pramipexole (tablets of 0.0625 mg, 0.125 mg and 0.25 mg) to be taken per os. Starting dose 0.0625 mg bid, with possible down titration after one week to 0.0625 mg qd or optional up titration to 0.125 mg bid, after the second week optional up titration to 0.125 mg tid, after the third week optional up titration to 0.25 mg bid.
Overall Study Adverse Event	1	2
Overall Study Lack of Efficacy	0	1
Overall Study Patient moving out of state	0	1

Baseline Characteristics

Pramipexole Pilot Phase II Study in Children and Adolescents With Tourette Disorder According to DSM-IV Criteria

Baseline characteristics by cohort

Measure	Placebo n=20 Participants Placebo tablets matching the Pramipexole tablets to be taken per os	Pramipexole n=43 Participants Pramipexole (tablets of 0.0625 mg, 0.125 mg and 0.25 mg) to be taken per os. Starting dose 0.0625 mg bid, with possible down titration after one week to 0.0625 mg qd or optional up titration to 0.125 mg bid, after the second week optional up titration to 0.125 mg tid, after the third week optional up titration to 0.25 mg bid.	Total n=63 Participants Total of all reporting groups
Age, Continuous	11.1 Years STANDARD_DEVIATION 3.2 • n=5 Participants	12.2 Years STANDARD_DEVIATION 2.4 • n=7 Participants	11.8 Years STANDARD_DEVIATION 2.7 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	8 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	35 Participants n=7 Participants	53 Participants n=5 Participants
Attention Deficit Hyperactive Disorder Intermediate	3 Number of Patients n=5 Participants	6 Number of Patients n=7 Participants	9 Number of Patients n=5 Participants
Attention Deficit Hyperactive Disorder Negative	9 Number of Patients n=5 Participants	22 Number of Patients n=7 Participants	31 Number of Patients n=5 Participants
Attention Deficit Hyperactive Disorder Positive	8 Number of Patients n=5 Participants	15 Number of Patients n=7 Participants	23 Number of Patients n=5 Participants
Duration of Tourettes syndrome 1-5 years	10 participants n=5 Participants	19 participants n=7 Participants	29 participants n=5 Participants
Duration of Tourettes syndrome Less than 1 years	6 participants n=5 Participants	12 participants n=7 Participants	18 participants n=5 Participants
Duration of Tourettes syndrome More than 5 years	4 participants n=5 Participants	12 participants n=7 Participants	16 participants n=5 Participants
Ethnicity, Customized Hispanic/Latino	2 Number of Patients n=5 Participants	5 Number of Patients n=7 Participants	7 Number of Patients n=5 Participants
Ethnicity, Customized Not Hispanic/Latino	18 Number of Patients n=5 Participants	38 Number of Patients n=7 Participants	56 Number of Patients n=5 Participants
Obsessive Compulsive Disorder Intermediate	1 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants
Obsessive Compulsive Disorder Negative	16 participants n=5 Participants	37 participants n=7 Participants	53 participants n=5 Participants
Obsessive Compulsive Disorder Positive	3 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants
Race, Customized Black/African American	2 participants n=5 Participants	4 participants n=7 Participants	6 participants n=5 Participants
Race, Customized White	18 participants n=5 Participants	39 participants n=7 Participants	57 participants n=5 Participants
Body Mass Index	20.085 kilograms/(meters squared) STANDARD_DEVIATION 5.324 • n=5 Participants	22.575 kilograms/(meters squared) STANDARD_DEVIATION 5.656 • n=7 Participants	21.784 kilograms/(meters squared) STANDARD_DEVIATION 5.632 • n=5 Participants
Height	150.7 centimeters STANDARD_DEVIATION 21.6 • n=5 Participants	155.3 centimeters STANDARD_DEVIATION 16.2 • n=7 Participants	153.8 centimeters STANDARD_DEVIATION 18 • n=5 Participants
Weight	47.48 kilograms STANDARD_DEVIATION 21.29 • n=5 Participants	55.87 kilograms STANDARD_DEVIATION 20.64 • n=7 Participants	53.21 kilograms STANDARD_DEVIATION 21.05 • n=5 Participants

PRIMARY outcome

Timeframe: baseline 6 weeks

Population: The Full Analysis Set (FAS) with last observation carried forward (LOCF).

Total Tic Score is the sum of ten individual ratings of the impairment due to tics. Each scale ranges from 0 (None/Absent) to 5 (Severe) and total score ranges from 0 to 50.

Analysis was adjusted for baseline total tic score and age as linear covariates.

Outcome measures

Measure	Placebo n=20 Participants Placebo tablets matching the Pramipexole tablets to be taken per os	Pramipexole n=42 Participants Pramipexole (tablets of 0.0625 mg, 0.125 mg and 0.25 mg) to be taken per os. Starting dose 0.0625 mg bid, with possible down titration after one week to 0.0625 mg qd or optional up titration to 0.125 mg bid, after the second week optional up titration to 0.125 mg tid, after the third week optional up titration to 0.25 mg bid.
Mean Change From Baseline in Total Tic Score of the Yale Global Tic Severity Scale	-7.17 score on a scale Standard Error 2.02	-7.16 score on a scale Standard Error 1.38

SECONDARY outcome

Timeframe: baseline 1 week

Population: The Full Analysis Set was composed of patients that provided a baseline and a post-baseline assessment in Total Tic Score. A total of 62 patients are included in the Full Analysis Set, 20 placebo patients and 42 pramipexole patients.

Total Tic Score is the sum of ten individual ratings of the impairment due to tics. Each scale ranges from 0 (None/Absent) to 5 (Severe) and total score ranges from 0 to 50

Outcome measures

Measure	Placebo n=20 Participants Placebo tablets matching the Pramipexole tablets to be taken per os	Pramipexole n=42 Participants Pramipexole (tablets of 0.0625 mg, 0.125 mg and 0.25 mg) to be taken per os. Starting dose 0.0625 mg bid, with possible down titration after one week to 0.0625 mg qd or optional up titration to 0.125 mg bid, after the second week optional up titration to 0.125 mg tid, after the third week optional up titration to 0.25 mg bid.
Mean Change From Baseline in Total Tic Score of the Yale Global Tic Severity Scale at Week 1	-3.7 score on a scale Standard Deviation 4.1	-4.1 score on a scale Standard Deviation 5.4

SECONDARY outcome

Timeframe: baseline and 2 weeks

Population: The Full Analysis Set was composed of patients that provided a baseline and a post-baseline assessment in Total Tic Score. A total of 62 patients are included in the Full Analysis Set, 20 placebo patients and 42 pramipexole patients.

Total Tic Score is the sum of ten individual ratings of the impairment due to tics. Each scale ranges from 0 (None/Absent) to 5 (Severe) and total score ranges from 0 to 50

Outcome measures

Measure	Placebo n=19 Participants Placebo tablets matching the Pramipexole tablets to be taken per os	Pramipexole n=41 Participants Pramipexole (tablets of 0.0625 mg, 0.125 mg and 0.25 mg) to be taken per os. Starting dose 0.0625 mg bid, with possible down titration after one week to 0.0625 mg qd or optional up titration to 0.125 mg bid, after the second week optional up titration to 0.125 mg tid, after the third week optional up titration to 0.25 mg bid.
Mean Change From Baseline in Total Tic Score of the Yale Global Tic Severity Scale at Week 2	-5.3 score on a scale Standard Deviation 7.9	-5 score on a scale Standard Deviation 7.4

SECONDARY outcome

Timeframe: baseline and 3 weeks

Population: The Full Analysis Set was composed of patients that provided a baseline and a post-baseline assessment in Total Tic Score. A total of 62 patients are included in the Full Analysis Set, 20 placebo patients and 42 pramipexole patients.

Total Tic Score is the sum of ten individual ratings of the impairment due to tics. Each scale ranges from 0 (None/Absent) to 5 (Severe) and total score ranges from 0 to 50

Outcome measures

Measure	Placebo n=19 Participants Placebo tablets matching the Pramipexole tablets to be taken per os	Pramipexole n=41 Participants Pramipexole (tablets of 0.0625 mg, 0.125 mg and 0.25 mg) to be taken per os. Starting dose 0.0625 mg bid, with possible down titration after one week to 0.0625 mg qd or optional up titration to 0.125 mg bid, after the second week optional up titration to 0.125 mg tid, after the third week optional up titration to 0.25 mg bid.
Mean Change From Baseline in Total Tic Score of the Yale Global Tic Severity Scale at Week 3	-6.2 score on a scale Standard Deviation 6.3	-5.4 score on a scale Standard Deviation 6.3

SECONDARY outcome

Timeframe: baseline and 4 weeks

Population: The Full Analysis Set was composed of patients that provided a baseline and a post-baseline assessment in Total Tic Score. A total of 62 patients are included in the Full Analysis Set, 20 placebo patients and 42 pramipexole patients.

Total Tic Score is the sum of ten individual ratings of the impairment due to tics. Each scale ranges from 0 (None/Absent) to 5 (Severe) and total score ranges from 0 to 50

Outcome measures

Measure	Placebo n=19 Participants Placebo tablets matching the Pramipexole tablets to be taken per os	Pramipexole n=40 Participants Pramipexole (tablets of 0.0625 mg, 0.125 mg and 0.25 mg) to be taken per os. Starting dose 0.0625 mg bid, with possible down titration after one week to 0.0625 mg qd or optional up titration to 0.125 mg bid, after the second week optional up titration to 0.125 mg tid, after the third week optional up titration to 0.25 mg bid.
Mean Change From Baseline in Total Tic Score of the Yale Global Tic Severity Scale at Week 4	-6 score on a scale Standard Deviation 7.9	-6.4 score on a scale Standard Deviation 7.3

SECONDARY outcome

Timeframe: baseline and 6 weeks

Population: The Full Analysis Set with last observation carried forward (LOCF).

Total Score is a rating of the overall impairment due to motor and phonic tics. The scale ranges from 0 (None) to 50 (Severe)

Outcome measures

Measure	Placebo n=20 Participants Placebo tablets matching the Pramipexole tablets to be taken per os	Pramipexole n=42 Participants Pramipexole (tablets of 0.0625 mg, 0.125 mg and 0.25 mg) to be taken per os. Starting dose 0.0625 mg bid, with possible down titration after one week to 0.0625 mg qd or optional up titration to 0.125 mg bid, after the second week optional up titration to 0.125 mg tid, after the third week optional up titration to 0.25 mg bid.
Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale Due to Motor and Phonic Tics at Week 6	-15.43 score on a scale Standard Error 4.44	-15.58 score on a scale Standard Error 3.03

SECONDARY outcome

Timeframe: baseline 1 week

Population: The Full Analysis Set was composed of patients that provided a baseline and a post-baseline assessment in Total Tic Score. A total of 62 patients are included in the Full Analysis Set, 20 placebo patients and 42 pramipexole patients.

Total Score is a rating of the overall impairment due to motor and phonic tics. The scale ranges from 0 (None) to 50 (Severe)

Outcome measures

Measure	Placebo n=20 Participants Placebo tablets matching the Pramipexole tablets to be taken per os	Pramipexole n=42 Participants Pramipexole (tablets of 0.0625 mg, 0.125 mg and 0.25 mg) to be taken per os. Starting dose 0.0625 mg bid, with possible down titration after one week to 0.0625 mg qd or optional up titration to 0.125 mg bid, after the second week optional up titration to 0.125 mg tid, after the third week optional up titration to 0.25 mg bid.
Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale Due to Motor and Phonic Tics at Week 1	-6.2 score on a scale Standard Deviation 13.3	-8.8 score on a scale Standard Deviation 11.1

SECONDARY outcome

Timeframe: baseline and 2 weeks

Population: The Full Analysis Set was composed of patients that provided a baseline and a post-baseline assessment in Total Tic Score. A total of 62 patients are included in the Full Analysis Set, 20 placebo patients and 42 pramipexole patients.

Total Score is a rating of the overall impairment due to motor and phonic tics. The scale ranges from 0 (None) to 50 (Severe)

Outcome measures

Measure	Placebo n=19 Participants Placebo tablets matching the Pramipexole tablets to be taken per os	Pramipexole n=41 Participants Pramipexole (tablets of 0.0625 mg, 0.125 mg and 0.25 mg) to be taken per os. Starting dose 0.0625 mg bid, with possible down titration after one week to 0.0625 mg qd or optional up titration to 0.125 mg bid, after the second week optional up titration to 0.125 mg tid, after the third week optional up titration to 0.25 mg bid.
Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale Due to Motor and Phonic Tics at Week 2	-9.5 score on a scale Standard Deviation 16.1	-10.6 score on a scale Standard Deviation 17.5

SECONDARY outcome

Timeframe: baseline and 3 weeks

Population: The Full Analysis Set was composed of patients that provided a baseline and a post-baseline assessment in Total Tic Score. A total of 62 patients are included in the Full Analysis Set, 20 placebo patients and 42 pramipexole patients.

Total Score is a rating of the overall impairment due to motor and phonic tics. The scale ranges from 0 (None) to 50 (Severe)

Outcome measures

Measure	Placebo n=19 Participants Placebo tablets matching the Pramipexole tablets to be taken per os	Pramipexole n=41 Participants Pramipexole (tablets of 0.0625 mg, 0.125 mg and 0.25 mg) to be taken per os. Starting dose 0.0625 mg bid, with possible down titration after one week to 0.0625 mg qd or optional up titration to 0.125 mg bid, after the second week optional up titration to 0.125 mg tid, after the third week optional up titration to 0.25 mg bid.
Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale Due to Motor and Phonic Tics at Week 3	-14.1 score on a scale Standard Deviation 17.2	-12.2 score on a scale Standard Deviation 15.7

SECONDARY outcome

Timeframe: baseline 4 weeks

Population: The Full Analysis Set was composed of patients that provided a baseline and a post-baseline assessment in Total Tic Score. A total of 62 patients are included in the Full Analysis Set, 20 placebo patients and 42 pramipexole patients.

Total Score is a rating of the overall impairment due to motor and phonic tics. The scale ranges from 0 (None) to 50 (Severe)

Outcome measures

Measure	Placebo n=19 Participants Placebo tablets matching the Pramipexole tablets to be taken per os	Pramipexole n=40 Participants Pramipexole (tablets of 0.0625 mg, 0.125 mg and 0.25 mg) to be taken per os. Starting dose 0.0625 mg bid, with possible down titration after one week to 0.0625 mg qd or optional up titration to 0.125 mg bid, after the second week optional up titration to 0.125 mg tid, after the third week optional up titration to 0.25 mg bid.
Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale Due to Motor and Phonic Tics at Week 4	-15.5 score on a scale Standard Deviation 18.2	-13.9 score on a scale Standard Deviation 15.7

SECONDARY outcome

Timeframe: baseline and Week 1

Population: The Full Analysis Set with last observation carried forward (LOCF).

Overall improvement during the last week compared to baseline ranging from 1 (very much improved), 2 (much improved), to 7 (very much worse). Responder has 'very much' or 'much' improvement. Non responder has less improvement than 'much' improvement.

Outcome measures

Measure	Placebo n=20 Participants Placebo tablets matching the Pramipexole tablets to be taken per os	Pramipexole n=42 Participants Pramipexole (tablets of 0.0625 mg, 0.125 mg and 0.25 mg) to be taken per os. Starting dose 0.0625 mg bid, with possible down titration after one week to 0.0625 mg qd or optional up titration to 0.125 mg bid, after the second week optional up titration to 0.125 mg tid, after the third week optional up titration to 0.25 mg bid.
Clinical Global Impressions - Improvement at 1 Week Responder	0 Number of Patients	5 Number of Patients
Clinical Global Impressions - Improvement at 1 Week Not Responder	20 Number of Patients	37 Number of Patients

SECONDARY outcome

Timeframe: baseline and Week 2

Population: The Full Analysis Set with last observation carried forward (LOCF).

Overall improvement during the last week compared to baseline ranging from 1 (very much improved), 2 (much improved), to 7 (very much worse). Responder has 'very much' or 'much' improvement. Non responder has less improvement than 'much' improvement.

Outcome measures

Measure	Placebo n=20 Participants Placebo tablets matching the Pramipexole tablets to be taken per os	Pramipexole n=42 Participants Pramipexole (tablets of 0.0625 mg, 0.125 mg and 0.25 mg) to be taken per os. Starting dose 0.0625 mg bid, with possible down titration after one week to 0.0625 mg qd or optional up titration to 0.125 mg bid, after the second week optional up titration to 0.125 mg tid, after the third week optional up titration to 0.25 mg bid.
Clinical Global Impressions - Improvement at Week 2 Responder	1 Number of Patients	6 Number of Patients
Clinical Global Impressions - Improvement at Week 2 Not Responder	19 Number of Patients	36 Number of Patients

SECONDARY outcome

Timeframe: baseline and Week 3

Population: The Full Analysis Set with last observation carried forward (LOCF).

Overall improvement during the last week compared to baseline ranging from 1 (very much improved), 2 (much improved), to 7 (very much worse). Responder has 'very much' or 'much' improvement. Non responder has less improvement than 'much' improvement.

Outcome measures

Measure	Placebo n=20 Participants Placebo tablets matching the Pramipexole tablets to be taken per os	Pramipexole n=42 Participants Pramipexole (tablets of 0.0625 mg, 0.125 mg and 0.25 mg) to be taken per os. Starting dose 0.0625 mg bid, with possible down titration after one week to 0.0625 mg qd or optional up titration to 0.125 mg bid, after the second week optional up titration to 0.125 mg tid, after the third week optional up titration to 0.25 mg bid.
Clinical Global Impressions - Improvement at Week 3 Responder	2 Number of Patients	5 Number of Patients
Clinical Global Impressions - Improvement at Week 3 Not Responder	18 Number of Patients	37 Number of Patients

SECONDARY outcome

Timeframe: baseline and Week 4

Population: The Full Analysis Set with last observation carried forward (LOCF).

Overall improvement during the last week compared to baseline ranging from 1 (very much improved), 2 (much improved), to 7 (very much worse). Responder has 'very much' or 'much' improvement. Non responder has less improvement than 'much' improvement.

Outcome measures

Measure	Placebo n=20 Participants Placebo tablets matching the Pramipexole tablets to be taken per os	Pramipexole n=42 Participants Pramipexole (tablets of 0.0625 mg, 0.125 mg and 0.25 mg) to be taken per os. Starting dose 0.0625 mg bid, with possible down titration after one week to 0.0625 mg qd or optional up titration to 0.125 mg bid, after the second week optional up titration to 0.125 mg tid, after the third week optional up titration to 0.25 mg bid.
Clinical Global Impressions - Improvement at Week 4 Responder	7 Number of Patients	6 Number of Patients
Clinical Global Impressions - Improvement at Week 4 Not Responder	13 Number of Patients	36 Number of Patients

SECONDARY outcome

Timeframe: baseline and Week 6

Population: The Full Analysis Set with last observation carried forward (LOCF).

Overall improvement during the last week compared to baseline ranging from 1 (very much improved), 2 (much improved), to 7 (very much worse). Responder has 'very much' or 'much' improvement. Non responder has less improvement than 'much' improvement.

Outcome measures

Measure	Placebo n=20 Participants Placebo tablets matching the Pramipexole tablets to be taken per os	Pramipexole n=42 Participants Pramipexole (tablets of 0.0625 mg, 0.125 mg and 0.25 mg) to be taken per os. Starting dose 0.0625 mg bid, with possible down titration after one week to 0.0625 mg qd or optional up titration to 0.125 mg bid, after the second week optional up titration to 0.125 mg tid, after the third week optional up titration to 0.25 mg bid.
Clinical Global Impressions - Improvement at Week 6 Responder	7 Number of Patients	11 Number of Patients
Clinical Global Impressions - Improvement at Week 6 Not Responder	13 Number of Patients	31 Number of Patients

SECONDARY outcome

Timeframe: baseline and Week 1

Population: The Full Analysis Set with last observation carried forward (LOCF).

Assessment of the overall severity of illness on a scale ranging from 1 (not at all ill) to 7 (the most extremely ill patients). Improved, Unchanged and Worsened responses correspond to changes from baseline of: -2 or less, -1 to +1, and 2 or greater.

Outcome measures

Measure	Placebo n=20 Participants Placebo tablets matching the Pramipexole tablets to be taken per os	Pramipexole n=42 Participants Pramipexole (tablets of 0.0625 mg, 0.125 mg and 0.25 mg) to be taken per os. Starting dose 0.0625 mg bid, with possible down titration after one week to 0.0625 mg qd or optional up titration to 0.125 mg bid, after the second week optional up titration to 0.125 mg tid, after the third week optional up titration to 0.25 mg bid.
Clinical Global Impressions - Severity of Illness at Week 1 Improved	0 Number of Patients	4 Number of Patients
Clinical Global Impressions - Severity of Illness at Week 1 Unchanged	20 Number of Patients	38 Number of Patients
Clinical Global Impressions - Severity of Illness at Week 1 Worsened	0 Number of Patients	0 Number of Patients

SECONDARY outcome

Timeframe: baseline and Week 2

Population: The Full Analysis Set with last observation carried forward (LOCF).

Assessment of the overall severity of illness on a scale ranging from 1 (not at all ill) to 7 (the most extremely ill patients). Improved, Unchanged and Worsened responses correspond to changes from baseline of: -2 or less, -1 to +1, and 2 or greater.

Outcome measures

Measure	Placebo n=20 Participants Placebo tablets matching the Pramipexole tablets to be taken per os	Pramipexole n=42 Participants Pramipexole (tablets of 0.0625 mg, 0.125 mg and 0.25 mg) to be taken per os. Starting dose 0.0625 mg bid, with possible down titration after one week to 0.0625 mg qd or optional up titration to 0.125 mg bid, after the second week optional up titration to 0.125 mg tid, after the third week optional up titration to 0.25 mg bid.
Clinical Global Impressions - Severity of Illness at Week 2 Improved	1 Number of Patients	4 Number of Patients
Clinical Global Impressions - Severity of Illness at Week 2 Unchanged	19 Number of Patients	37 Number of Patients
Clinical Global Impressions - Severity of Illness at Week 2 Worsened	0 Number of Patients	1 Number of Patients

SECONDARY outcome

Timeframe: baseline and Week 3

Population: The Full Analysis Set with last observation carried forward (LOCF).

Assessment of the overall severity of illness on a scale ranging from 1 (not at all ill) to 7 (the most extremely ill patients). Improved, Unchanged and Worsened responses correspond to changes from baseline of: -2 or less, -1 to +1, and 2 or greater.

Outcome measures

Measure	Placebo n=20 Participants Placebo tablets matching the Pramipexole tablets to be taken per os	Pramipexole n=42 Participants Pramipexole (tablets of 0.0625 mg, 0.125 mg and 0.25 mg) to be taken per os. Starting dose 0.0625 mg bid, with possible down titration after one week to 0.0625 mg qd or optional up titration to 0.125 mg bid, after the second week optional up titration to 0.125 mg tid, after the third week optional up titration to 0.25 mg bid.
Clinical Global Impressions - Severity of Illness at Week 3 Improved	3 Number of Patients	4 Number of Patients
Clinical Global Impressions - Severity of Illness at Week 3 Unchanged	17 Number of Patients	37 Number of Patients
Clinical Global Impressions - Severity of Illness at Week 3 Worsened	0 Number of Patients	1 Number of Patients

SECONDARY outcome

Timeframe: baseline and Week 4

Population: The Full Analysis Set with last observation carried forward (LOCF).

Assessment of the overall severity of illness on a scale ranging from 1 (not at all ill) to 7 (the most extremely ill patients). Improved, Unchanged and Worsened responses correspond to changes from baseline of: -2 or less, -1 to +1, and 2 or greater.

Outcome measures

Measure	Placebo n=20 Participants Placebo tablets matching the Pramipexole tablets to be taken per os	Pramipexole n=42 Participants Pramipexole (tablets of 0.0625 mg, 0.125 mg and 0.25 mg) to be taken per os. Starting dose 0.0625 mg bid, with possible down titration after one week to 0.0625 mg qd or optional up titration to 0.125 mg bid, after the second week optional up titration to 0.125 mg tid, after the third week optional up titration to 0.25 mg bid.
Clinical Global Impressions - Severity of Illness at Week 4 Improved	4 Number of Patients	4 Number of Patients
Clinical Global Impressions - Severity of Illness at Week 4 Unchanged	16 Number of Patients	38 Number of Patients
Clinical Global Impressions - Severity of Illness at Week 4 Worsened	0 Number of Patients	0 Number of Patients

SECONDARY outcome

Timeframe: baseline and Week 6

Population: The Full Analysis Set with last observation carried forward (LOCF).

Assessment of the overall severity of illness on a scale ranging from 1 (not at all ill) to 7 (the most extremely ill patients). Improved, Unchanged and Worsened responses correspond to changes from baseline of: -2 or less, -1 to +1, and 2 or greater.

Outcome measures

Measure	Placebo n=20 Participants Placebo tablets matching the Pramipexole tablets to be taken per os	Pramipexole n=42 Participants Pramipexole (tablets of 0.0625 mg, 0.125 mg and 0.25 mg) to be taken per os. Starting dose 0.0625 mg bid, with possible down titration after one week to 0.0625 mg qd or optional up titration to 0.125 mg bid, after the second week optional up titration to 0.125 mg tid, after the third week optional up titration to 0.25 mg bid.
Clinical Global Impressions - Severity of Illness at Week 6 Improved	4 Number of Patients	10 Number of Patients
Clinical Global Impressions - Severity of Illness at Week 6 Unchanged	16 Number of Patients	32 Number of Patients
Clinical Global Impressions - Severity of Illness at Week 6 Worsened	0 Number of Patients	0 Number of Patients

SECONDARY outcome

Timeframe: baseline and Week 1

Population: The Full Analysis Set with last observation carried forward (LOCF).

Assessment of the change of the patient's overall condition during the last week compared to the patient's condition at baseline on a scale ranging from 1 (very much better) to 7 (very much worse). A responder is defined as having a response of very much (1) or much better (2).

Outcome measures

Measure	Placebo n=20 Participants Placebo tablets matching the Pramipexole tablets to be taken per os	Pramipexole n=42 Participants Pramipexole (tablets of 0.0625 mg, 0.125 mg and 0.25 mg) to be taken per os. Starting dose 0.0625 mg bid, with possible down titration after one week to 0.0625 mg qd or optional up titration to 0.125 mg bid, after the second week optional up titration to 0.125 mg tid, after the third week optional up titration to 0.25 mg bid.
Patient Global Impression at Week 1 Responder	4 Number of Patients	7 Number of Patients
Patient Global Impression at Week 1 Not Responder	16 Number of Patients	35 Number of Patients

SECONDARY outcome

Timeframe: baseline and Week 2

Population: The Full Analysis Set with last observation carried forward (LOCF).

Assessment of the change of the patient's overall condition during the last week compared to the patient's condition at baseline on a scale ranging from 1 (very much better) to 7 (very much worse). A responder is defined as having a response of very much (1) or much better (2).

Outcome measures

Measure	Placebo n=20 Participants Placebo tablets matching the Pramipexole tablets to be taken per os	Pramipexole n=42 Participants Pramipexole (tablets of 0.0625 mg, 0.125 mg and 0.25 mg) to be taken per os. Starting dose 0.0625 mg bid, with possible down titration after one week to 0.0625 mg qd or optional up titration to 0.125 mg bid, after the second week optional up titration to 0.125 mg tid, after the third week optional up titration to 0.25 mg bid.
Patient Global Impression at Week 2 Responder	6 Number of Patients	9 Number of Patients
Patient Global Impression at Week 2 Not Responder	14 Number of Patients	33 Number of Patients

SECONDARY outcome

Timeframe: baseline and Week 3

Population: The Full Analysis Set with last observation carried forward (LOCF).

Assessment of the change of the patient's overall condition during the last week compared to the patient's condition at baseline on a scale ranging from 1 (very much better) to 7 (very much worse). A responder is defined as having a response of very much (1) or much better (2).

Outcome measures

Measure	Placebo n=20 Participants Placebo tablets matching the Pramipexole tablets to be taken per os	Pramipexole n=42 Participants Pramipexole (tablets of 0.0625 mg, 0.125 mg and 0.25 mg) to be taken per os. Starting dose 0.0625 mg bid, with possible down titration after one week to 0.0625 mg qd or optional up titration to 0.125 mg bid, after the second week optional up titration to 0.125 mg tid, after the third week optional up titration to 0.25 mg bid.
Patient Global Impression at Week 3 Responder	5 Number of Patients	7 Number of Patients
Patient Global Impression at Week 3 Not Responder	15 Number of Patients	35 Number of Patients

SECONDARY outcome

Timeframe: baseline and Week 4

Population: The Full Analysis Set with last observation carried forward (LOCF).

Assessment of the change of the patient's overall condition during the last week compared to the patient's condition at baseline on a scale ranging from 1 (very much better) to 7 (very much worse). A responder is defined as having a response of very much (1) or much better (2).

Outcome measures

Measure	Placebo n=20 Participants Placebo tablets matching the Pramipexole tablets to be taken per os	Pramipexole n=42 Participants Pramipexole (tablets of 0.0625 mg, 0.125 mg and 0.25 mg) to be taken per os. Starting dose 0.0625 mg bid, with possible down titration after one week to 0.0625 mg qd or optional up titration to 0.125 mg bid, after the second week optional up titration to 0.125 mg tid, after the third week optional up titration to 0.25 mg bid.
Patient Global Impression at Week 4 Responder	4 Number of Patients	7 Number of Patients
Patient Global Impression at Week 4 Not Responder	16 Number of Patients	35 Number of Patients

SECONDARY outcome

Timeframe: baseline and Week 6

Population: The Full Analysis Set with last observation carried forward (LOCF).

Assessment of the change of the patient's overall condition during the last week compared to the patient's condition at baseline on a scale ranging from 1 (very much better) to 7 (very much worse). A responder is defined as having a response of very much (1) or much better (2).

Outcome measures

Measure	Placebo n=20 Participants Placebo tablets matching the Pramipexole tablets to be taken per os	Pramipexole n=42 Participants Pramipexole (tablets of 0.0625 mg, 0.125 mg and 0.25 mg) to be taken per os. Starting dose 0.0625 mg bid, with possible down titration after one week to 0.0625 mg qd or optional up titration to 0.125 mg bid, after the second week optional up titration to 0.125 mg tid, after the third week optional up titration to 0.25 mg bid.
Patient Global Impression at Week 6 Responder	6 Number of Patients	12 Number of Patients
Patient Global Impression at Week 6 Not Responder	14 Number of Patients	30 Number of Patients

SECONDARY outcome

Timeframe: baseline and Week 6

Population: Full Analysis Set (FAS).

Outcome measures

Measure	Placebo n=19 Participants Placebo tablets matching the Pramipexole tablets to be taken per os	Pramipexole n=40 Participants Pramipexole (tablets of 0.0625 mg, 0.125 mg and 0.25 mg) to be taken per os. Starting dose 0.0625 mg bid, with possible down titration after one week to 0.0625 mg qd or optional up titration to 0.125 mg bid, after the second week optional up titration to 0.125 mg tid, after the third week optional up titration to 0.25 mg bid.
Clinically Significant Abnormalities in Vital Signs (Orthostatic Reaction and Pulse Rate), and Serum Chemistry. Phosphate - increase	2 participants	5 participants
Clinically Significant Abnormalities in Vital Signs (Orthostatic Reaction and Pulse Rate), and Serum Chemistry. Bilirubin, total - increase	0 participants	1 participants
Clinically Significant Abnormalities in Vital Signs (Orthostatic Reaction and Pulse Rate), and Serum Chemistry. Tachycardia	0 participants	1 participants
Clinically Significant Abnormalities in Vital Signs (Orthostatic Reaction and Pulse Rate), and Serum Chemistry. Orthostatic hypotension	1 participants	4 participants

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 13 other events

Deaths: 0 deaths

Pramipexole

Serious events: 0 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=20 participants at risk Placebo tablets matching the Pramipexole tablets to be taken per os	Pramipexole n=43 participants at risk Pramipexole (tablets of 0.0625 mg, 0.125 mg and 0.25 mg) to be taken per os. Starting dose 0.0625 mg bid, with possible down titration after one week to 0.0625 mg qd or optional up titration to 0.125 mg bid, after the second week optional up titration to 0.125 mg tid, after the third week optional up titration to 0.25 mg bid.
Infections and infestations Gastroenteritis viral	5.0% 1/20 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.	0.00% 0/43 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.
Metabolism and nutrition disorders Dehydration	5.0% 1/20 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.	0.00% 0/43 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.

Other adverse events

Measure	Placebo n=20 participants at risk Placebo tablets matching the Pramipexole tablets to be taken per os	Pramipexole n=43 participants at risk Pramipexole (tablets of 0.0625 mg, 0.125 mg and 0.25 mg) to be taken per os. Starting dose 0.0625 mg bid, with possible down titration after one week to 0.0625 mg qd or optional up titration to 0.125 mg bid, after the second week optional up titration to 0.125 mg tid, after the third week optional up titration to 0.25 mg bid.
Gastrointestinal disorders Abdominal pain upper	5.0% 1/20 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.	7.0% 3/43 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.
Gastrointestinal disorders Diarrhoea	10.0% 2/20 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.	7.0% 3/43 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.
Gastrointestinal disorders Nausea	10.0% 2/20 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.	18.6% 8/43 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.
Gastrointestinal disorders Vomiting	0.00% 0/20 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.	11.6% 5/43 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.
General disorders Fatigue	10.0% 2/20 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.	9.3% 4/43 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.
General disorders Pyrexia	10.0% 2/20 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.	4.7% 2/43 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.
Infections and infestations Nasopharyngitis	10.0% 2/20 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.	4.7% 2/43 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.
Infections and infestations Upper respiratory tract infection	5.0% 1/20 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.	7.0% 3/43 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.
Musculoskeletal and connective tissue disorders Myalgia	5.0% 1/20 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.	9.3% 4/43 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.
Nervous system disorders Dizziness	15.0% 3/20 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.	7.0% 3/43 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.
Nervous system disorders Headache	25.0% 5/20 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.	27.9% 12/43 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.
Nervous system disorders Somnolence	5.0% 1/20 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.	7.0% 3/43 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.
Psychiatric disorders Sleep disorder	0.00% 0/20 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.	7.0% 3/43 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.
Psychiatric disorders Tic	10.0% 2/20 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.	2.3% 1/43 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.
Respiratory, thoracic and mediastinal disorders Cough	10.0% 2/20 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.	7.0% 3/43 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/20 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.	7.0% 3/43 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	15.0% 3/20 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.	7.0% 3/43 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.
Vascular disorders Orthostatic hypotension	5.0% 1/20 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.	9.3% 4/43 • All events with an onset after the first dose of study medication and up to a period of 48 hours after the last dose of study medication were assigned to the treatment period.

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