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

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00558467
• Collaborator: (none)
• Enrollment: 63
• Locations: 16
• Arms: 2
• Patients Per Site: 3.9

Study Details

Study Description

Brief Summary

A randomized, double-blind, placebo-controlled, flexible dose study to evaluate efficacy and safety of Pramipexole versus placebo for 6 weeks in children (age 6-17) diagnosed with Tourette Disorder according to DSM IV criteria. The primary efficacy measure will be the Total Tic Score (TTS) of the Yale Global Tic Severity Scale (YGTSS) at 6 weeks.

Condition or Disease	Intervention/Treatment	Phase
Tourette Syndrome	Drug: pramipexole immediate release (IR); Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 63 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled, Flexible Dose Study to Evaluate Efficacy and Safety of Pramipexole Immediate Release (0.125-0.5mg/Day) Versus Placebo for 6 Weeks in Children and Adolescents (Age 6-17 Inclusive) Diagnosed With Tourette Disorder According to DSM IV Criteria.
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: Jun 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Other: Pramipexole	Drug: pramipexole immediate release (IR)
Placebo Comparator: Placebo	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Mean Change From Baseline in Total Tic Score of the Yale Global Tic Severity Scale [baseline 6 weeks]

   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.

Secondary Outcome Measures

1. Mean Change From Baseline in Total Tic Score of the Yale Global Tic Severity Scale at Week 1 [baseline 1 week]

   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

2. Mean Change From Baseline in Total Tic Score of the Yale Global Tic Severity Scale at Week 2 [baseline and 2 weeks]

   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

3. Mean Change From Baseline in Total Tic Score of the Yale Global Tic Severity Scale at Week 3 [baseline and 3 weeks]

   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

4. Mean Change From Baseline in Total Tic Score of the Yale Global Tic Severity Scale at Week 4 [baseline and 4 weeks]

   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

5. Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale Due to Motor and Phonic Tics at Week 6 [baseline and 6 weeks]

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

6. Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale Due to Motor and Phonic Tics at Week 1 [baseline 1 week]

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

7. Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale Due to Motor and Phonic Tics at Week 2 [baseline and 2 weeks]

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

8. Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale Due to Motor and Phonic Tics at Week 3 [baseline and 3 weeks]

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

9. Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale Due to Motor and Phonic Tics at Week 4 [baseline 4 weeks]

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

10. Clinical Global Impressions - Improvement at 1 Week [baseline and Week 1]

    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.

11. Clinical Global Impressions - Improvement at Week 2 [baseline and Week 2]

    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.

12. Clinical Global Impressions - Improvement at Week 3 [baseline and Week 3]

    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.

13. Clinical Global Impressions - Improvement at Week 4 [baseline and Week 4]

    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.

14. Clinical Global Impressions - Improvement at Week 6 [baseline and Week 6]

    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.

15. Clinical Global Impressions - Severity of Illness at Week 1 [baseline and Week 1]

    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.

16. Clinical Global Impressions - Severity of Illness at Week 2 [baseline and Week 2]

    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.

17. Clinical Global Impressions - Severity of Illness at Week 3 [baseline and Week 3]

    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.

18. Clinical Global Impressions - Severity of Illness at Week 4 [baseline and Week 4]

    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.

19. Clinical Global Impressions - Severity of Illness at Week 6 [baseline and Week 6]

    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.

20. Patient Global Impression at Week 1 [baseline and Week 1]

    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).

21. Patient Global Impression at Week 2 [baseline and Week 2]

    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).

22. Patient Global Impression at Week 3 [baseline and Week 3]

    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).

23. Patient Global Impression at Week 4 [baseline and Week 4]

    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).

24. Patient Global Impression at Week 6 [baseline and Week 6]

    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).

25. Clinically Significant Abnormalities in Vital Signs (Orthostatic Reaction and Pulse Rate), and Serum Chemistry. [baseline and Week 6]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male of female patients 6-17 yrs.

• Written informed consent.

• Diagnosed with Tourette's Disorder with a > or equal to 22 on the Total Tic Score at baseline.

• Diagnosed with Tourette's Disorder when administering the Diagnostic Interview Schedule for Children.

• Having at least 1 tic/day.

• Women of childbearing age must have a negative serum pregnancy test at screening and must use a medically accepted contraceptive method.

• Either a newly diagnosed patient or a patient diagnosed with Tourette's Disorder who can safely discontinue treatment.

• Having a body weight of > or equal to 20 kg (44 lbs).

Exclusion Criteria:

• Any women of childbearing age having a positive serum pregnancy test at screening.

• Patients who have clinically significant renal disease or serum creatinine greater than 1.0 mg/dL at screening.

• Lab results at screening: hemoglobin below lower limit of normal which is determined to be clinically significant; Thyroid Stimulating Hormone (TSH), triiodothyronine (T3) or thyroxine (T4) clinically significant; clinically significant abnormalities in labs.

• Other clinically significant metabolic-endocrine, hematological, gastrointestinal disease, pulmonary disease which would preclude the patient from participating in this study.

• History of Schizophrenia or any psychotic disorder, history of mental disorders or any present Axis I psychiatric disorder according to Diagnostic and Statistic Manual of Mental Disorders Fourth Edition (DSM-IV) requiring any medical therapy except for patients with a diagnosis of attention deficit hyperactivity disorder (ADHD) or obsessive-compulsive disorder (OCD) who are not on therapy.

• History of/or clinical signs of epilepsy or seizures other than fever related seizures in early childhood.

• History of/or clinical signs of any malignant neoplasm.

• Allergic response to pramipexole.

• Had previous treatment with dopamine agonists other than pramipexole within 14 days prior to baseline visit.

• Had any other medical treatment for Tourette's Disorder besides the study medication within 28 days prior to baseline visit.

• Had withdrawal symptoms of any medication at screening or at the baseline visit.

• Having a Kaufman Brief Intelligence Test (KBIT IQ) score <70 at screening.

• Having a children's Yale-Brown obsessive-compulsive scale (CY-BOCS) score of >15 at baseline.

• Patients who meet criteria for Restless Legs Syndrome and or Periodic Limb Movement disorder.

• Patients with severe asthma.

• Patients that have initiated psychotherapy for Tourette's Disorder, OCD or ADHD within 3 mths of starting the trial.

• Patients receiving psychological, cognitive and/or behavioral treatments greater than 3 mths prior to start of trial for Tourette's Disorder, OCD, and/or ADHD who will have changes in treatment plan.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	248.644.0026 Boehringer Ingelheim Investigational Site	Bradenton	Florida	United States
2	248.644.0025 Boehringer Ingelheim Investigational Site	Tampa	Florida	United States
3	248.644.0006 Boehringer Ingelheim Investigational Site	Columbus	Georgia	United States
4	248.644.0012 Boehringer Ingelheim Investigational Site	Chicago	Illinois	United States
5	248.644.0005 Boehringer Ingelheim Investigational Site	Cambridge	Massachusetts	United States
6	248.644.0003 Boehringer Ingelheim Investigational Site	Manhasset	New York	United States
7	248.644.0009 Boehringer Ingelheim Investigational Site	New York	New York	United States
8	248.644.0018 Boehringer Ingelheim Investigational Site	New York	New York	United States
9	248.644.0013 Boehringer Ingelheim Investigational Site	Orangeburg	New York	United States
10	248.644.0029 Boehringer Ingelheim Investigational Site	Oklahoma City	Oklahoma	United States
11	248.644.0010 Boehringer Ingelheim Investigational Site	Providence	Rhode Island	United States
12	248.644.0030 Boehringer Ingelheim Investigational Site	Memphis	Tennessee	United States
13	248.644.0008 Boehringer Ingelheim Investigational Site	Houston	Texas	United States
14	248.644.0023 Boehringer Ingelheim Investigational Site	Norfolk	Virginia	United States
15	248.644.49001 Boehringer Ingelheim Investigational Site	Hannover		Germany
16	248.644.49004 Boehringer Ingelheim Investigational Site	Ulm		Germany

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info
• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT00558467
• Other Study ID Numbers: 248.644
• First Posted: Nov 15, 2007
• Last Update Posted: May 16, 2014
• Last Verified: Mar 1, 2014

• Additional relevant MeSH terms: Tourette Syndrome; Pramipexole

Study Results

Participant Flow

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablets matching the Pramipexole tablets to be taken per os	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.
Period Title: Overall Study
STARTED	20	43
COMPLETED	19	39
NOT COMPLETED	1	4

Baseline Characteristics

Arm/Group Title	Placebo	Pramipexole	Total
Arm/Group Description	Placebo tablets matching the Pramipexole tablets to be taken per os	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 of all reporting groups
Overall Participants	20	43	63
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	11.1 (3.2)	12.2 (2.4)	11.8 (2.7)
Sex: Female, Male (Count of Participants)
Female	2 10%	8 18.6%	10 15.9%
Male	18 90%	35 81.4%	53 84.1%
Attention Deficit Hyperactive Disorder (Number of Patients) [Number]
Intermediate	3	6	9
Negative	9	22	31
Positive	8	15	23
Duration of Tourettes syndrome (participants) [Number]
1-5 years	10 50%	19 44.2%	29 46%
Less than 1 years	6 30%	12 27.9%	18 28.6%
More than 5 years	4 20%	12 27.9%	16 25.4%
Ethnicity, Customized (Number of Patients) [Number]
Hispanic/Latino	2	5	7
Not Hispanic/Latino	18	38	56
Obsessive Compulsive Disorder (participants) [Number]
Intermediate	1 5%	3 7%	4 6.3%
Negative	16 80%	37 86%	53 84.1%
Positive	3 15%	3 7%	6 9.5%
Race, Customized (participants) [Number]
Black/African American	2 10%	4 9.3%	6 9.5%
White	18 90%	39 90.7%	57 90.5%
Body Mass Index (kilograms/(meters squared)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms/(meters squared)]	20.085 (5.324)	22.575 (5.656)	21.784 (5.632)
Height (centimeters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeters]	150.7 (21.6)	155.3 (16.2)	153.8 (18)
Weight (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	47.48 (21.29)	55.87 (20.64)	53.21 (21.05)

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline in Total Tic Score of the Yale Global Tic Severity Scale
Description	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.
Time Frame	baseline 6 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablets matching the Pramipexole tablets to be taken per os	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.
Measure Participants	20	42
Least Squares Mean (Standard Error) [score on a scale]	-7.17 (2.02)	-7.16 (1.38)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pramipexole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.996
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares mean difference
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 95%; -4.95 to 4.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Mean Change From Baseline in Total Tic Score of the Yale Global Tic Severity Scale at Week 1
Description	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
Time Frame	baseline 1 week

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablets matching the Pramipexole tablets to be taken per os	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.
Measure Participants	20	42
Mean (Standard Deviation) [score on a scale]	-3.7 (4.1)	-4.1 (5.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pramipexole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square means difference
	Estimated Value	-3.94
	Confidence Interval	(2-Sided) 95%; -5.81 to -2.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Mean Change From Baseline in Total Tic Score of the Yale Global Tic Severity Scale at Week 2
Description	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
Time Frame	baseline and 2 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablets matching the Pramipexole tablets to be taken per os	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.
Measure Participants	19	41
Mean (Standard Deviation) [score on a scale]	-5.3 (7.9)	-5 (7.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pramipexole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square means difference
	Estimated Value	-5.30
	Confidence Interval	(2-Sided) 95%; -7.21 to -3.39
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Mean Change From Baseline in Total Tic Score of the Yale Global Tic Severity Scale at Week 3
Description	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
Time Frame	baseline and 3 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablets matching the Pramipexole tablets to be taken per os	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.
Measure Participants	19	41
Mean (Standard Deviation) [score on a scale]	-6.2 (6.3)	-5.4 (6.3)

5. Secondary Outcome

Title	Mean Change From Baseline in Total Tic Score of the Yale Global Tic Severity Scale at Week 4
Description	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
Time Frame	baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablets matching the Pramipexole tablets to be taken per os	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.
Measure Participants	19	40
Mean (Standard Deviation) [score on a scale]	-6 (7.9)	-6.4 (7.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pramipexole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square means difference
	Estimated Value	-5.97
	Confidence Interval	(2-Sided) 95%; -7.88 to -4.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale Due to Motor and Phonic Tics at Week 6
Description	Total Score is a rating of the overall impairment due to motor and phonic tics. The scale ranges from 0 (None) to 50 (Severe)
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablets matching the Pramipexole tablets to be taken per os	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.
Measure Participants	20	42
Least Squares Mean (Standard Error) [score on a scale]	-15.43 (4.44)	-15.58 (3.03)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pramipexole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9780
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean differnce
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) 95%; -11.05 to 10.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale Due to Motor and Phonic Tics at Week 1
Description	Total Score is a rating of the overall impairment due to motor and phonic tics. The scale ranges from 0 (None) to 50 (Severe)
Time Frame	baseline 1 week

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablets matching the Pramipexole tablets to be taken per os	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.
Measure Participants	20	42
Mean (Standard Deviation) [score on a scale]	-6.2 (13.3)	-8.8 (11.1)

8. Secondary Outcome

Title	Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale Due to Motor and Phonic Tics at Week 2
Description	Total Score is a rating of the overall impairment due to motor and phonic tics. The scale ranges from 0 (None) to 50 (Severe)
Time Frame	baseline and 2 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablets matching the Pramipexole tablets to be taken per os	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.
Measure Participants	19	41
Mean (Standard Deviation) [score on a scale]	-9.5 (16.1)	-10.6 (17.5)

9. Secondary Outcome

Title	Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale Due to Motor and Phonic Tics at Week 3
Description	Total Score is a rating of the overall impairment due to motor and phonic tics. The scale ranges from 0 (None) to 50 (Severe)
Time Frame	baseline and 3 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablets matching the Pramipexole tablets to be taken per os	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.
Measure Participants	19	41
Mean (Standard Deviation) [score on a scale]	-14.1 (17.2)	-12.2 (15.7)

10. Secondary Outcome

Title	Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale Due to Motor and Phonic Tics at Week 4
Description	Total Score is a rating of the overall impairment due to motor and phonic tics. The scale ranges from 0 (None) to 50 (Severe)
Time Frame	baseline 4 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablets matching the Pramipexole tablets to be taken per os	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.
Measure Participants	19	40
Mean (Standard Deviation) [score on a scale]	-15.5 (18.2)	-13.9 (15.7)

11. Secondary Outcome

Title	Clinical Global Impressions - Improvement at 1 Week
Description	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.
Time Frame	baseline and Week 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablets matching the Pramipexole tablets to be taken per os	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.
Measure Participants	20	42
Responder	0	5
Not Responder	20	37

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pramipexole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1052
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

12. Secondary Outcome

Title	Clinical Global Impressions - Improvement at Week 2
Description	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.
Time Frame	baseline and Week 2

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablets matching the Pramipexole tablets to be taken per os	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.
Measure Participants	20	42
Responder	1	6
Not Responder	19	36

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pramipexole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2274
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

13. Secondary Outcome

Title	Clinical Global Impressions - Improvement at Week 3
Description	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.
Time Frame	baseline and Week 3

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablets matching the Pramipexole tablets to be taken per os	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.
Measure Participants	20	42
Responder	2	5
Not Responder	18	37

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pramipexole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7691
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

14. Secondary Outcome

Title	Clinical Global Impressions - Improvement at Week 4
Description	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.
Time Frame	baseline and Week 4

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablets matching the Pramipexole tablets to be taken per os	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.
Measure Participants	20	42
Responder	7	6
Not Responder	13	36

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pramipexole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0674
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

15. Secondary Outcome

Title	Clinical Global Impressions - Improvement at Week 6
Description	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.
Time Frame	baseline and Week 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablets matching the Pramipexole tablets to be taken per os	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.
Measure Participants	20	42
Responder	7	11
Not Responder	13	31

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pramipexole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4944
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

16. Secondary Outcome

Title	Clinical Global Impressions - Severity of Illness at Week 1
Description	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.
Time Frame	baseline and Week 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablets matching the Pramipexole tablets to be taken per os	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.
Measure Participants	20	42
Improved	0	4
Unchanged	20	38
Worsened	0	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pramipexole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.162
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

17. Secondary Outcome

Title	Clinical Global Impressions - Severity of Illness at Week 2
Description	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.
Time Frame	baseline and Week 2

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablets matching the Pramipexole tablets to be taken per os	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.
Measure Participants	20	42
Improved	1	4
Unchanged	19	37
Worsened	0	1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pramipexole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6375
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

18. Secondary Outcome

Title	Clinical Global Impressions - Severity of Illness at Week 3
Description	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.
Time Frame	baseline and Week 3

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablets matching the Pramipexole tablets to be taken per os	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.
Measure Participants	20	42
Improved	3	4
Unchanged	17	37
Worsened	0	1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pramipexole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6625
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

19. Secondary Outcome

Title	Clinical Global Impressions - Severity of Illness at Week 4
Description	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.
Time Frame	baseline and Week 4

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablets matching the Pramipexole tablets to be taken per os	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.
Measure Participants	20	42
Improved	4	4
Unchanged	16	38
Worsened	0	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pramipexole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2664
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

20. Secondary Outcome

Title	Clinical Global Impressions - Severity of Illness at Week 6
Description	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.
Time Frame	baseline and Week 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablets matching the Pramipexole tablets to be taken per os	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.
Measure Participants	20	42
Improved	4	10
Unchanged	16	32
Worsened	0	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pramipexole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7302
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

21. Secondary Outcome

Title	Patient Global Impression at Week 1
Description	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).
Time Frame	baseline and Week 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablets matching the Pramipexole tablets to be taken per os	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.
Measure Participants	20	42
Responder	4	7
Not Responder	16	35

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pramipexole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7723
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

22. Secondary Outcome

Title	Patient Global Impression at Week 2
Description	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).
Time Frame	baseline and Week 2

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablets matching the Pramipexole tablets to be taken per os	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.
Measure Participants	20	42
Responder	6	9
Not Responder	14	33

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pramipexole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4852
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

23. Secondary Outcome

Title	Patient Global Impression at Week 3
Description	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).
Time Frame	baseline and Week 3

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablets matching the Pramipexole tablets to be taken per os	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.
Measure Participants	20	42
Responder	5	7
Not Responder	15	35

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pramipexole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4607
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

24. Secondary Outcome

Title	Patient Global Impression at Week 4
Description	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).
Time Frame	baseline and Week 4

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablets matching the Pramipexole tablets to be taken per os	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.
Measure Participants	20	42
Responder	4	7
Not Responder	16	35

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pramipexole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7723
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

25. Secondary Outcome

Title	Patient Global Impression at Week 6
Description	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).
Time Frame	baseline and Week 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablets matching the Pramipexole tablets to be taken per os	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.
Measure Participants	20	42
Responder	6	12
Not Responder	14	30

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pramipexole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9389
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

26. Secondary Outcome

Title	Clinically Significant Abnormalities in Vital Signs (Orthostatic Reaction and Pulse Rate), and Serum Chemistry.
Time Frame	baseline and Week 6

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS).

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablets matching the Pramipexole tablets to be taken per os	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.
Measure Participants	19	40
Phosphate - increase	2 10%	5 11.6%
Bilirubin, total - increase	0 0%	1 2.3%
Tachycardia	0 0%	1 2.3%
Orthostatic hypotension	1 5%	4 9.3%

Adverse Events

Time Frame	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.
Arm/Group Title	Placebo		Pramipexole
Arm/Group Description	Placebo tablets matching the Pramipexole tablets to be taken per os		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.
All Cause Mortality
	Placebo		Pramipexole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Pramipexole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/20 (5%)		0/43 (0%)
Infections and infestations
Gastroenteritis viral	1/20 (5%)		0/43 (0%)
Metabolism and nutrition disorders
Dehydration	1/20 (5%)		0/43 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Pramipexole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/20 (65%)		25/43 (58.1%)
Gastrointestinal disorders
Abdominal pain upper	1/20 (5%)		3/43 (7%)
Diarrhoea	2/20 (10%)		3/43 (7%)
Nausea	2/20 (10%)		8/43 (18.6%)
Vomiting	0/20 (0%)		5/43 (11.6%)
General disorders
Fatigue	2/20 (10%)		4/43 (9.3%)
Pyrexia	2/20 (10%)		2/43 (4.7%)
Infections and infestations
Nasopharyngitis	2/20 (10%)		2/43 (4.7%)
Upper respiratory tract infection	1/20 (5%)		3/43 (7%)
Musculoskeletal and connective tissue disorders
Myalgia	1/20 (5%)		4/43 (9.3%)
Nervous system disorders
Dizziness	3/20 (15%)		3/43 (7%)
Headache	5/20 (25%)		12/43 (27.9%)
Somnolence	1/20 (5%)		3/43 (7%)
Psychiatric disorders
Sleep disorder	0/20 (0%)		3/43 (7%)
Tic	2/20 (10%)		1/43 (2.3%)
Respiratory, thoracic and mediastinal disorders
Cough	2/20 (10%)		3/43 (7%)
Dyspnoea	0/20 (0%)		3/43 (7%)
Oropharyngeal pain	3/20 (15%)		3/43 (7%)
Vascular disorders
Orthostatic hypotension	1/20 (5%)		4/43 (9.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.