Open-label Extension Study of Pramipexole in the Treatment of Children and Adolescents With Tourette Syndrome

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00681863
• Collaborator: (none)
• Enrollment: 45
• Locations: 14
• Arms: 5
• Patients Per Site: 3.2

Study Details

Study Description

Brief Summary

The primary objective of this open-label, flexible dose study is to assess the safety and efficacy of pramipexole over a 24-week period in children and adolescents (age 6-17 years inclusive) diagnosed with Tourette Syndrome according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria and who have completed either Study 248.641 (NCT 00681863) or 248.644 (NCT 00558467).

Condition or Disease	Intervention/Treatment	Phase
Tourette Syndrome	Drug: pramipexole 0.125 mg BID; Drug: pramipexole 0.0625 mg QD; Drug: pramipexole 0.125 mg TID; Drug: pramipexole 0.25 mg BID; Drug: pramipexole 0.0625 mg BID	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 45 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open Label Extension Study With Pramipexole (PPX) in Children With Tourette Syndrome
• Study Start Date: May 1, 2008
• Actual Primary Completion Date: Oct 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: pramipexole 0.0625 mg BID (twice daily) all patients to receive one tablet of pramipexole 0.0625 mg BID for first 4 weeks (flexible dosing for all other arms)	Drug: pramipexole 0.0625 mg BID; 0.0625 mg BID given for first 4 wks of treatment
Active Comparator: pramipexole 0.0625 mg QD (once daily) patients to receive one tablet of pramipexole 0.0625 mg QD	Drug: pramipexole 0.0625 mg QD; dose down titrated for those patients unable to tolerate the 0.0625 mg BID dosing
Active Comparator: pramipexole 0.125 mg BID patients to receive one tablet of pramipexole 0.125 mg BID	Drug: pramipexole 0.125 mg BID; titrated dose for those patients whose symptoms were not controlled on the 0.0625 mg BID dose
Active Comparator: pramipexole 0.125 mg TID (three times daily) patients to receive one tablet of pramipexole 0.125 mg TID	Drug: pramipexole 0.125 mg TID; titrated up for those patients whose symptoms were not adequately controlled on 0.125 mg BID dose
Active Comparator: pramipexole 0.25 mg BID patients to receive one tablet of pramipexole 0.25 mg BID	Drug: pramipexole 0.25 mg BID; titrated for those patients whose symptoms were not adequately controlled on 0.125 mg TID dose

Outcome Measures

Primary Outcome Measures

1. Patients With Adverse Events Leading to Discontinuation of Trial Drug [24 Weeks]

   Number of patients with Adverse Events leading to discontinuation of trial drug

Secondary Outcome Measures

1. Mean Change From Baseline in Total Tic Score (TTS) of the Yale Global Tic Severity Scale [baseline and week 24]

   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 Score of the Yale Global Tic Severity Scale [baseline and Week 24 (end of treatment visit)]

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

3. Mean Change From Baseline in Total Tic Score (TTS) of the Yale Global Tic Severity Scale [baseline and Week 1]

   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 (TTS) of the Yale Global Tic Severity Scale [baseline and Week 2]

   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 Tic Score (TTS) of the Yale Global Tic Severity Scale [baseline and Week 3]

   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.

6. Mean Change From Baseline in Total Tic Score (TTS) of the Yale Global Tic Severity Scale [baseline and week 4]

   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.

7. Mean Change From Baseline in Total Tic Score (TTS) of the Yale Global Tic Severity Scale [baseline and Week 8]

   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.

8. Mean Change From Baseline in Total Tic Score (TTS) of the Yale Global Tic Severity Scale [baseline and Week 12]

   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.

9. Mean Change From Baseline in Total Tic Score (TTS) of the Yale Global Tic Severity Scale [baseline and Week 16]

   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.

10. Mean Change From Baseline in Total Tic Score (TTS) of the Yale Global Tic Severity Scale [baseline and Week 20]

    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.

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

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

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

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

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

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

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

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

15. Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale [baseline and Week 8]

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

16. Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale [baseline and Week 12]

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

17. Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale [baseline and Week 16]

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

18. Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale [baseline and Week 20]

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

19. Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale [baseline and Week 24]

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

20. Clinical Global Impressions - Severity of Illness [week 24]

    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.

21. Clinical Global Impressions - Severity of Illness, Categorized [week 24]

    Assessment of the overall severity of illness on a scale ranging from 1 (not at all ill) to 7 (among the most extremely ill patients). 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.

22. Clinical Global Impressions - Improvement [week 1]

    Assessment of the overall improvement during the last week compared to the patient's condition at baseline on a scale ranging from 1 (very much improved) to 7 (very much worse).

23. Clinical Global Impressions - Improvement [week 2]

    Assessment of the overall improvement during the last week compared to the patient's condition at baseline on a scale ranging from 1 (very much improved) to 7 (very much worse).

24. Clinical Global Impressions - Improvement [week 3]

    Assessment of the overall improvement during the last week compared to the patient's condition at baseline on a scale ranging from 1 (very much improved) to 7 (very much worse).

25. Clinical Global Impressions - Improvement [week 4]

    Assessment of the overall improvement during the last week compared to the patient's condition at baseline on a scale ranging from 1 (very much improved) to 7 (very much worse).

26. Clinical Global Impressions - Improvement [week 8]

    Assessment of the overall improvement during the last week compared to the patient's condition at baseline on a scale ranging from 1 (very much improved) to 7 (very much worse).

27. Clinical Global Impressions - Improvement [week 12]

    Assessment of the overall improvement during the last week compared to the patient's condition at baseline on a scale ranging from 1 (very much improved) to 7 (very much worse).

28. Clinical Global Impressions - Improvement [week 16]

    Assessment of the overall improvement during the last week compared to the patient's condition at baseline on a scale ranging from 1 (very much improved) to 7 (very much worse).

29. Clinical Global Impressions - Improvement [week 20]

    Assessment of the overall improvement during the last week compared to the patient's condition at baseline on a scale ranging from 1 (very much improved) to 7 (very much worse).

30. Clinical Global Impressions - Improvement [week 24]

    Assessment of the overall improvement during the last week compared to the patient's condition at baseline on a scale ranging from 1 (very much improved) to 7 (very much worse).

31. Patient Global Impression - Improvement [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).

32. Patient Global Impression - Improvement [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).

33. Patient Global Impression - Improvement [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).

34. Patient Global Impression - Improvement [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).

35. Patient Global Impression - Improvement [week 8]

    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).

36. Patient Global Impression - Improvement [week 12]

    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).

37. Patient Global Impression - Improvement [week 16]

    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).

38. Patient Global Impression - Improvement [week 20]

    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).

39. Patient Global Impression - Improvement [week 24]

    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).

40. Frequency of Patients With Possible Clinically Significant Abnormalities for Laboratory Parameters [Baseline and 24 weeks]

    Frequency of patients with possible clinically significant abnormalities for laboratory parameters (blood hematology and electrolyte assessments, serum chemistry, including follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol for pubertal female patients, prolactin in all patients, testosterone in pubertal male patients, urine analysis)

Eligibility Criteria

Criteria

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

Inclusion criteria

1. Male or female patients aged 6-17 years at the time of enrollment into study 248.641 or 248.644 and who have completed study 248.641 or 248.644.

2. Written informed consent provided by the patient's parent (or legal guardian) and assent provided by the patient consistent with International Conference on Harmonization (ICH) Good Clinical Practice (GCP) and local Institutional Review Board (IRB) requirements for children obtained prior to any study procedures being performed.

3. Ability and willingness to comply with study treatment regimen and to complete study assessments.

4. Females of childbearing potential having a negative serum pregnancy test at Visit 1.

5. Females of childbearing potential must be using a medically accepted contraceptive method throughout the study. Acceptable methods of birth control are limited to: Intra-Uterine Device (IUD), oral, implantable, injectable contraceptives or estrogen patch, double barrier method (spermicide + diaphragm), or abstinence at the discretion of the investigator

Exclusion criteria

1. Breastfeeding females.

2. Development of any clinical condition in the preceding trial that in the investigator's opinion could be worsened by treatment with pramipexole.

3. Clinically significant renal disease or serum creatinine out of this range: 0.3 1.0 mg/dL for patients aged 3-12 years and 0.5-1.4 mg/dL for patients aged 13+ years.

4. Any of the following lab results at screening:

Hemoglobin (Hgb) below lower limit of normal (LLN) which is determined to be clinically significant Basal thyroid stimulating hormone (TSH), triiodothyronine (T3) or thyroxine (T4) clinically significant (at the investigator's discretion) out of normal range at screening (if not caused by substitution therapy according the investigator's opinion) Patients with any clinically significant abnormalities in laboratory parameters at screening at the investigator's discretion.

1. Other clinically significant metabolic-endocrine, hematological, gastrointestinal disease, or pulmonary disease (such as severe asthma) in the opinion of the investigator that would preclude the patient from participating in this study.

2. History or presence of schizophrenia or any psychotic disorder. History or presence of any psychiatric disorder requiring medical therapy with the exception for patients with a diagnosis of Tourette Syndrome (TS), Attention Deficit Hyperactivity Disorder (ADHD) or Obsessive Compulsive Disorder (OCD) who are not on therapy other than pramipexole.

3. History or presence of clinical signs of epilepsy or seizures other than fever-related seizures in early childhood.

4. History or presence of clinical signs of any malignant neoplasm including suspicious undiagnosed skin lesion (which may be melanoma), melanoma, or a history of melanoma.

5. History of any other medical treatment for TS besides the study medication within 28 days prior to the baseline visit (14 days prior to baseline for guanfacine, 14 days prior to baseline for dopamine agonists, 14 days prior to baseline for L-Dopa, 35 days prior to baseline for fluoxetine).

6. Patients receiving psychotherapy are excluded unless they started the treatment at least 3 months prior to starting the trial and no changes in treatment are planned for the duration of the study.

7. Allergic response to pramipexole or the inactive ingredients in its tablet formulation.

8. Non-compliance with study medication (defined as less than 80% or more than 120%) during the preceding Study 248.641 or 248.644.

9. Concurrent participation in another clinical trial using any investigational drug since completion of the preceding Study 248.641 or 248.644.

10. Any other conditions, that in the opinion of the investigator, would interfere with the evaluation of the results or constitute a health hazard for the patient.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	248.642.0026 Boehringer Ingelheim Investigational Site	Bradenton	Florida	United States
2	248.642.0025 Boehringer Ingelheim Investigational Site	Tampa	Florida	United States
3	248.642.0006 Boehringer Ingelheim Investigational Site	Columbus	Georgia	United States
4	248.642.0005 Boehringer Ingelheim Investigational Site	Cambridge	Massachusetts	United States
5	248.642.0003 Boehringer Ingelheim Investigational Site	Manhasset	New York	United States
6	248.642.0009 Boehringer Ingelheim Investigational Site	New York	New York	United States
7	248.642.0018 Boehringer Ingelheim Investigational Site	New York	New York	United States
8	248.642.0013 Boehringer Ingelheim Investigational Site	Orangeburg	New York	United States
9	248.642.0029 Boehringer Ingelheim Investigational Site	Oklahoma City	Oklahoma	United States
10	248.642.0010 Boehringer Ingelheim Investigational Site	Providence	Rhode Island	United States
11	248.642.0030 Boehringer Ingelheim Investigational Site	Memphis	Tennessee	United States
12	248.642.0008 Boehringer Ingelheim Investigational Site	Houston	Texas	United States
13	248.642.0023 Boehringer Ingelheim Investigational Site	Norfolk	Virginia	United States
14	248.642.49004 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: NCT00681863
• Other Study ID Numbers: 248.642; 2008-000342-32
• First Posted: May 21, 2008
• Last Update Posted: May 23, 2014
• Last Verified: May 1, 2014

• Additional relevant MeSH terms: Tourette Syndrome; Syndrome; Pramipexole

Study Results

Participant Flow

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID (twice daily), down-titration to 0.0625 QD (once daily) if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID (three times daily) and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Period Title: Overall Study
STARTED	45
COMPLETED	22
NOT COMPLETED	23

Baseline Characteristics

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Overall Participants	45
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	11.8 (2.8)
Sex: Female, Male (Count of Participants)
Female	9 20%
Male	36 80%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	6 13.3%
Not Hispanic or Latino	38 84.4%
Unknown or Not Reported	1 2.2%
Race/Ethnicity, Customized (participants) [Number]
Black or African American	5 11.1%
White	40 88.9%
Duration of Tourettes Syndrome (Number) [Number]
More than 5 years	10 22.2%
Less than 1 year	15 33.3%
1 to 5 years	20 44.4%
Height (centimeters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeters]	152.6 (19.4)
Weight (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	53.01 (21.58)
Body mass index (kilograms/square meter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms/square meter]	22.064 (5.930)
Body temperature (Degrees centigrade) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Degrees centigrade]	36.752 (0.718)
Respiration (breaths/minute) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [breaths/minute]	17.4 (2.0)
Obsessive Compulsive Disorder (Number) [Number]
Positive	4 8.9%
Intermediate	4 8.9%
Negative	37 82.2%
Attention Deficit Hyperactive Disorder (participants) [Number]
Positive	17 37.8%
Intermediate	6 13.3%
Negative	22 48.9%
Treatment received in previous trial (NCT00558467) (Number) [Number]
Received placebo	14 31.1%
Received pramipexole	31 68.9%

Outcome Measures

1. Secondary Outcome

Title	Mean Change From Baseline in Total Tic Score (TTS) 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.
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	45
Mean (Standard Deviation) [Score on a scale]	-9.8 (8.9)

2. Secondary Outcome

Title	Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale
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 Week 24 (end of treatment visit)

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) with Last Observation Carried Forward (LOCF).

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	45
Mean (Standard Deviation) [Score on a scale]	-22.0 (21.0)

3. Secondary Outcome

Title	Mean Change From Baseline in Total Tic Score (TTS) 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.
Time Frame	baseline and Week 1

Outcome Measure Data

Analysis Population Description

Observed Cases Full Analysis Set (OC FAS). All participants in FAS having observed data at the particular timepoint.

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	45
Mean (Standard Deviation) [Score on a scale]	-7.2 (8.5)

4. Secondary Outcome

Title	Mean Change From Baseline in Total Tic Score (TTS) 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.
Time Frame	baseline and Week 2

Outcome Measure Data

Analysis Population Description

Observed Cases Full Analysis Set (OC FAS). All participants in FAS having observed data at the particular timepoint.

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	45
Mean (Standard Deviation) [Score on a scale]	-8.3 (7.7)

5. Secondary Outcome

Title	Mean Change From Baseline in Total Tic Score (TTS) 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.
Time Frame	baseline and Week 3

Outcome Measure Data

Analysis Population Description

Observed Cases Full Analysis Set (OC FAS). All participants in FAS having observed data at the particular timepoint.

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	44
Mean (Standard Deviation) [Score on a scale]	-8.6 (8.6)

6. Secondary Outcome

Title	Mean Change From Baseline in Total Tic Score (TTS) 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.
Time Frame	baseline and week 4

Outcome Measure Data

Analysis Population Description

Observed Cases Full Analysis Set (OC FAS). All participants in FAS having observed data at the particular timepoint.

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	44
Mean (Standard Deviation) [Score on a scale]	-9.3 (9.7)

7. Secondary Outcome

Title	Mean Change From Baseline in Total Tic Score (TTS) 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.
Time Frame	baseline and Week 8

Outcome Measure Data

Analysis Population Description

Observed Cases Full Analysis Set (OC FAS). All participants in FAS having observed data at the particular timepoint.

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	41
Mean (Standard Deviation) [Score on a scale]	-10.7 (9.4)

8. Secondary Outcome

Title	Mean Change From Baseline in Total Tic Score (TTS) 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.
Time Frame	baseline and Week 12

Outcome Measure Data

Analysis Population Description

Observed Cases Full Analysis Set (OC FAS). All participants in FAS having observed data at the particular timepoint.

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	35
Mean (Standard Deviation) [Score on a scale]	-12.3 (9.0)

9. Secondary Outcome

Title	Mean Change From Baseline in Total Tic Score (TTS) 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.
Time Frame	baseline and Week 16

Outcome Measure Data

Analysis Population Description

Observed Cases Full Analysis Set (OC FAS). All participants in FAS having observed data at the particular timepoint.

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	32
Mean (Standard Deviation) [Score on a scale]	-12.4 (9.3)

10. Secondary Outcome

Title	Mean Change From Baseline in Total Tic Score (TTS) 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.
Time Frame	baseline and Week 20

Outcome Measure Data

Analysis Population Description

Observed Cases Full Analysis Set (OC FAS). All participants in FAS having observed data at the particular timepoint.

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	26
Mean (Standard Deviation) [Score on a scale]	-11.7 (11.3)

11. Secondary Outcome

Title	Mean Change From Baseline in Total Tic Score (TTS) 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.
Time Frame	baseline and Week 24

Outcome Measure Data

Analysis Population Description

Observed Cases Full Analysis Set (OC FAS). All participants in FAS having observed data at the particular timepoint.

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	22
Mean (Standard Deviation) [Score on a scale]	-9.3 (10.4)

12. Secondary Outcome

Title	Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale
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 Week 1

Outcome Measure Data

Analysis Population Description

Observed Cases Full Analysis Set (OC FAS). All participants in FAS having observed data at the particular timepoint.

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	45
Mean (Standard Deviation) [Score on a scale]	-14.5 (18.2)

13. Secondary Outcome

Title	Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale
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 Week 2

Outcome Measure Data

Analysis Population Description

Observed Cases Full Analysis Set (OC FAS). All participants in FAS having observed data at the particular timepoint.

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	45
Mean (Standard Deviation) [Score on a scale]	-17.4 (17.6)

14. Secondary Outcome

Title	Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale
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 Week 3

Outcome Measure Data

Analysis Population Description

Observed Cases Full Analysis Set (OC FAS). All participants in FAS having observed data at the particular timepoint.

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	44
Mean (Standard Deviation) [Score on a scale]	-18.4 (19.8)

15. Secondary Outcome

Title	Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale
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 Week 4

Outcome Measure Data

Analysis Population Description

Observed Cases Full Analysis Set (OC FAS). All participants in FAS having observed data at the particular timepoint.

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	44
Mean (Standard Deviation) [Score on a scale]	-20.9 (21.5)

16. Secondary Outcome

Title	Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale
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 Week 8

Outcome Measure Data

Analysis Population Description

Observed Cases Full Analysis Set (OC FAS). All participants in FAS having observed data at the particular timepoint.

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	41
Mean (Standard Deviation) [Score on a scale]	-22.4 (21.9)

17. Secondary Outcome

Title	Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale
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 Week 12

Outcome Measure Data

Analysis Population Description

Observed Cases Full Analysis Set (OC FAS). All participants in FAS having observed data at the particular timepoint.

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	35
Mean (Standard Deviation) [Score on a scale]	-27.7 (20.9)

18. Secondary Outcome

Title	Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale
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 Week 16

Outcome Measure Data

Analysis Population Description

Observed Cases Full Analysis Set (OC FAS). All participants in FAS having observed data at the particular timepoint.

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	32
Mean (Standard Deviation) [Score on a scale]	-28.3 (20.2)

19. Secondary Outcome

Title	Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale
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 Week 20

Outcome Measure Data

Analysis Population Description

Observed Cases Full Analysis Set (OC FAS). All participants in FAS having observed data at the particular timepoint.

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	26
Mean (Standard Deviation) [Score on a scale]	-26.7 (24.9)

20. Secondary Outcome

Title	Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale
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 Week 24

Outcome Measure Data

Analysis Population Description

Observed Cases Full Analysis Set (OC FAS). All participants in FAS having observed data at the particular timepoint.

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	22
Mean (Standard Deviation) [Score on a scale]	-22.0 (23.6)

21. Secondary Outcome

Title	Clinical Global Impressions - Severity of Illness
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	week 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	42
Mean (Standard Deviation) [score on a scale]	-1.1 (1.1)

22. Secondary Outcome

Title	Clinical Global Impressions - Severity of Illness, Categorized
Description	Assessment of the overall severity of illness on a scale ranging from 1 (not at all ill) to 7 (among the most extremely ill patients). 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	week 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	42
Improved (change score <= -2)	11 24.4%
Unchanged (change score of -1, 0, or +1)	31 68.9%
Worsened (change score >= +2)	0 0%

23. Secondary Outcome

Title	Clinical Global Impressions - Improvement
Description	Assessment of the overall improvement during the last week compared to the patient's condition at baseline on a scale ranging from 1 (very much improved) to 7 (very much worse).
Time Frame	week 1

Outcome Measure Data

Analysis Population Description

This outcome measure was not analyzed due to the premature ending of the trial.

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	0

24. Secondary Outcome

Title	Clinical Global Impressions - Improvement
Description	Assessment of the overall improvement during the last week compared to the patient's condition at baseline on a scale ranging from 1 (very much improved) to 7 (very much worse).
Time Frame	week 2

Outcome Measure Data

Analysis Population Description

This outcome measure was not analyzed due to the premature ending of the trial.

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	0

25. Primary Outcome

Title	Patients With Adverse Events Leading to Discontinuation of Trial Drug
Description	Number of patients with Adverse Events leading to discontinuation of trial drug
Time Frame	24 Weeks

Outcome Measure Data

Analysis Population Description

Treated set

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	45
Number [participants]	1 2.2%

26. Secondary Outcome

Title	Clinical Global Impressions - Improvement
Description	Assessment of the overall improvement during the last week compared to the patient's condition at baseline on a scale ranging from 1 (very much improved) to 7 (very much worse).
Time Frame	week 3

Outcome Measure Data

Analysis Population Description

This outcome measure was not analyzed due to the premature ending of the trial.

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	0

27. Secondary Outcome

Title	Clinical Global Impressions - Improvement
Description	Assessment of the overall improvement during the last week compared to the patient's condition at baseline on a scale ranging from 1 (very much improved) to 7 (very much worse).
Time Frame	week 4

Outcome Measure Data

Analysis Population Description

This outcome measure was not analyzed due to the premature ending of the trial.

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	0

28. Secondary Outcome

Title	Clinical Global Impressions - Improvement
Description	Assessment of the overall improvement during the last week compared to the patient's condition at baseline on a scale ranging from 1 (very much improved) to 7 (very much worse).
Time Frame	week 8

Outcome Measure Data

Analysis Population Description

This outcome measure was not analyzed due to the premature ending of the trial.

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	0

29. Secondary Outcome

Title	Clinical Global Impressions - Improvement
Description	Assessment of the overall improvement during the last week compared to the patient's condition at baseline on a scale ranging from 1 (very much improved) to 7 (very much worse).
Time Frame	week 12

Outcome Measure Data

Analysis Population Description

This outcome measure was not analyzed due to the premature ending of the trial.

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	0

30. Secondary Outcome

Title	Clinical Global Impressions - Improvement
Description	Assessment of the overall improvement during the last week compared to the patient's condition at baseline on a scale ranging from 1 (very much improved) to 7 (very much worse).
Time Frame	week 16

Outcome Measure Data

Analysis Population Description

This outcome measure was not analyzed due to the premature ending of the trial.

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	0

31. Secondary Outcome

Title	Clinical Global Impressions - Improvement
Description	Assessment of the overall improvement during the last week compared to the patient's condition at baseline on a scale ranging from 1 (very much improved) to 7 (very much worse).
Time Frame	week 20

Outcome Measure Data

Analysis Population Description

This outcome measure was not analyzed due to the premature ending of the trial.

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	0

32. Secondary Outcome

Title	Clinical Global Impressions - Improvement
Description	Assessment of the overall improvement during the last week compared to the patient's condition at baseline on a scale ranging from 1 (very much improved) to 7 (very much worse).
Time Frame	week 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	45
Responder (Much improved or Very much improved)	22 48.9%
Not Responder	23 51.1%

33. Secondary Outcome

Title	Patient Global Impression - Improvement
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	week 1

Outcome Measure Data

Analysis Population Description

This outcome measure was not analyzed due to the premature ending of the trial.

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	0

34. Secondary Outcome

Title	Patient Global Impression - Improvement
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	week 2

Outcome Measure Data

Analysis Population Description

This outcome measure was not analyzed due to the premature ending of the trial.

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	0

35. Secondary Outcome

Title	Patient Global Impression - Improvement
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	week 3

Outcome Measure Data

Analysis Population Description

This outcome measure was not analyzed due to the premature ending of the trial.

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	0

36. Secondary Outcome

Title	Patient Global Impression - Improvement
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	week 4

Outcome Measure Data

Analysis Population Description

This outcome measure was not analyzed due to the premature ending of the trial.

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	0

37. Secondary Outcome

Title	Patient Global Impression - Improvement
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	week 8

Outcome Measure Data

Analysis Population Description

This outcome measure was not analyzed due to the premature ending of the trial.

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	0

38. Secondary Outcome

Title	Patient Global Impression - Improvement
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	week 12

Outcome Measure Data

Analysis Population Description

This outcome measure was not analyzed due to the premature ending of the trial.

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	0

39. Secondary Outcome

Title	Patient Global Impression - Improvement
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	week 16

Outcome Measure Data

Analysis Population Description

This outcome measure was not analyzed due to the premature ending of the trial.

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	0

40. Secondary Outcome

Title	Patient Global Impression - Improvement
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	week 20

Outcome Measure Data

Analysis Population Description

This outcome measure was not analyzed due to the premature ending of the trial.

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	0

41. Secondary Outcome

Title	Patient Global Impression - Improvement
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	week 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	45
Responder (Much better or Very much better)	17 37.8%
Not Responder	28 62.2%

42. Secondary Outcome

Title	Frequency of Patients With Possible Clinically Significant Abnormalities for Laboratory Parameters
Description	Frequency of patients with possible clinically significant abnormalities for laboratory parameters (blood hematology and electrolyte assessments, serum chemistry, including follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol for pubertal female patients, prolactin in all patients, testosterone in pubertal male patients, urine analysis)
Time Frame	Baseline and 24 weeks

Outcome Measure Data

Analysis Population Description

Observed Cases Treated set (OC TS). All participants in Treated Set having observed data at the particular timepoint.

Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
Measure Participants	43
Haemoglobin - decrease	2 4.4%
Eosinophils - increase	3 6.7%
Phosphate - increase	2 4.4%
Alkaline phosphatase - increase	1 2.2%

Adverse Events

Time Frame	up to 24 weeks
Adverse Event Reporting Description	At each visit, the Investigator asked the patient and parent(s) (legal guardians) to elucidate any adverse events that may have occurred since the last visit in order to document if any adverse events had occurred, and carefully recorded the adverse event information reported.
Arm/Group Title	Pramipexole
Arm/Group Description	4 weeks individual dose titration starting with 0.0625 mg BID, down-titration to 0.0625 QD if not tolerated, and next steps 0.125 mg BID, 0.125 mg TID and 0.25 mg BID, according to efficacy assessment; established optimal dose for the remainder of the 24-week treatment period.
All Cause Mortality
	Pramipexole
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Pramipexole
	Affected / at Risk (%)	# Events
Total	1/45 (2.2%)
Nervous system disorders
Syncope	1/45 (2.2%)
Other (Not Including Serious) Adverse Events
	Pramipexole
	Affected / at Risk (%)	# Events
Total	35/45 (77.8%)
Gastrointestinal disorders
Abdominal pain upper	4/45 (8.9%)
Nausea	8/45 (17.8%)
Vomiting	4/45 (8.9%)
General disorders
Fatigue	6/45 (13.3%)
Pyrexia	4/45 (8.9%)
Immune system disorders
Hypersensitivity	4/45 (8.9%)
Infections and infestations
Nasopharyngitis	5/45 (11.1%)
Upper respiratory tract infection	4/45 (8.9%)
Injury, poisoning and procedural complications
Skin laceration	3/45 (6.7%)
Metabolism and nutrition disorders
Increased appetite	4/45 (8.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	4/45 (8.9%)
Myalgia	3/45 (6.7%)
Nervous system disorders
Dizziness	3/45 (6.7%)
Headache	9/45 (20%)
Somnolence	3/45 (6.7%)
Psychiatric disorders
Tic	4/45 (8.9%)
Respiratory, thoracic and mediastinal disorders
Cough	3/45 (6.7%)
Vascular disorders
Orthostatic hypotension	3/45 (6.7%)

Limitations/Caveats

The sponsor cancelled this trial prematurely. Thus, enrollment for 248.642 (NCT00681863) was significantly less than what was planned (120 planned vs. 45 entered). Therefore, the objectives of this study could not be fully assessed.

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