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

Tourette Syndrome Clinical Trial

Official title:

Open Label Extension Study With Pramipexole (PPX) in Children With Tourette Syndrome

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00681863
• Other study ID #: 248.642
• Secondary ID: 2008-000342-32
• Status: Terminated
• Phase: Phase 3
• First received: May 19, 2008
• Last updated: May 7, 2014
• Start date: May 2008

Study information

• Verified date: May 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: Comitê Nacional de Ética em Pesquisa Clínica - CONEPGermany: BfArM-Federal Authorities for Drugs and Medical DevicesUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 45
• Est. primary completion date: October 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years to 17 Years

Eligibility

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.

5. 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.

6. 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.

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

8. 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.

9. 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).

10. 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.

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

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

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

14. 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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Syndrome
• Tourette Syndrome

Intervention

Drug:
• pramipexole 0.125 mg BID
titrated dose for those patients whose symptoms were not controlled on the 0.0625 mg BID dose
• pramipexole 0.0625 mg QD
dose down titrated for those patients unable to tolerate the 0.0625 mg BID dosing
• pramipexole 0.125 mg TID
titrated up for those patients whose symptoms were not adequately controlled on 0.125 mg BID dose
• pramipexole 0.25 mg BID
titrated for those patients whose symptoms were not adequately controlled on 0.125 mg TID dose
• pramipexole 0.0625 mg BID
0.0625 mg BID given for first 4 wks of treatment

Locations

Country	Name	City	State
Germany	248.642.49004 Boehringer Ingelheim Investigational Site	Ulm
United States	248.642.0026 Boehringer Ingelheim Investigational Site	Bradenton	Florida
United States	248.642.0005 Boehringer Ingelheim Investigational Site	Cambridge	Massachusetts
United States	248.642.0006 Boehringer Ingelheim Investigational Site	Columbus	Georgia
United States	248.642.0008 Boehringer Ingelheim Investigational Site	Houston	Texas
United States	248.642.0003 Boehringer Ingelheim Investigational Site	Manhasset	New York
United States	248.642.0030 Boehringer Ingelheim Investigational Site	Memphis	Tennessee
United States	248.642.0009 Boehringer Ingelheim Investigational Site	New York	New York
United States	248.642.0018 Boehringer Ingelheim Investigational Site	New York	New York
United States	248.642.0023 Boehringer Ingelheim Investigational Site	Norfolk	Virginia
United States	248.642.0029 Boehringer Ingelheim Investigational Site	Oklahoma City	Oklahoma
United States	248.642.0013 Boehringer Ingelheim Investigational Site	Orangeburg	New York
United States	248.642.0010 Boehringer Ingelheim Investigational Site	Providence	Rhode Island
United States	248.642.0025 Boehringer Ingelheim Investigational Site	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Patients With Adverse Events Leading to Discontinuation of Trial Drug	Number of patients with Adverse Events leading to discontinuation of trial drug	24 Weeks	No
Secondary	Mean Change From Baseline in Total Tic Score (TTS) of the Yale Global Tic Severity Scale	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.	baseline and week 24	No
Secondary	Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale	Total Score is a rating of the overall impairment due to motor and phonic tics. The scale ranges from 0 (None) to 50 (Severe).	baseline and Week 24 (end of treatment visit)	No
Secondary	Mean Change From Baseline in Total Tic Score (TTS) of the Yale Global Tic Severity Scale	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.	baseline and Week 1	No
Secondary	Mean Change From Baseline in Total Tic Score (TTS) of the Yale Global Tic Severity Scale	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.	baseline and Week 2	No
Secondary	Mean Change From Baseline in Total Tic Score (TTS) of the Yale Global Tic Severity Scale	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.	baseline and Week 3	No
Secondary	Mean Change From Baseline in Total Tic Score (TTS) of the Yale Global Tic Severity Scale	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.	baseline and week 4	No
Secondary	Mean Change From Baseline in Total Tic Score (TTS) of the Yale Global Tic Severity Scale	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.	baseline and Week 8	No
Secondary	Mean Change From Baseline in Total Tic Score (TTS) of the Yale Global Tic Severity Scale	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.	baseline and Week 12	No
Secondary	Mean Change From Baseline in Total Tic Score (TTS) of the Yale Global Tic Severity Scale	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.	baseline and Week 16	No
Secondary	Mean Change From Baseline in Total Tic Score (TTS) of the Yale Global Tic Severity Scale	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.	baseline and Week 20	No
Secondary	Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale	Total Score is a rating of the overall impairment due to motor and phonic tics. The scale ranges from 0 (None) to 50 (Severe).	baseline and Week 1	No
Secondary	Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale	Total Score is a rating of the overall impairment due to motor and phonic tics. The scale ranges from 0 (None) to 50 (Severe).	baseline and Week 2	No
Secondary	Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale	Total Score is a rating of the overall impairment due to motor and phonic tics. The scale ranges from 0 (None) to 50 (Severe).	baseline and Week 3	No
Secondary	Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale	Total Score is a rating of the overall impairment due to motor and phonic tics. The scale ranges from 0 (None) to 50 (Severe).	baseline and Week 4	No
Secondary	Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale	Total Score is a rating of the overall impairment due to motor and phonic tics. The scale ranges from 0 (None) to 50 (Severe).	baseline and Week 8	No
Secondary	Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale	Total Score is a rating of the overall impairment due to motor and phonic tics. The scale ranges from 0 (None) to 50 (Severe).	baseline and Week 12	No
Secondary	Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale	Total Score is a rating of the overall impairment due to motor and phonic tics. The scale ranges from 0 (None) to 50 (Severe).	baseline and Week 16	No
Secondary	Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale	Total Score is a rating of the overall impairment due to motor and phonic tics. The scale ranges from 0 (None) to 50 (Severe).	baseline and Week 20	No
Secondary	Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale	Total Score is a rating of the overall impairment due to motor and phonic tics. The scale ranges from 0 (None) to 50 (Severe).	baseline and Week 24	No
Secondary	Clinical Global Impressions - Severity of Illness	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.	week 24	No
Secondary	Clinical Global Impressions - Severity of Illness, Categorized	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.	week 24	No
Secondary	Clinical Global Impressions - Improvement	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).	week 1	No
Secondary	Clinical Global Impressions - Improvement	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).	week 2	No
Secondary	Clinical Global Impressions - Improvement	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).	week 3	No
Secondary	Clinical Global Impressions - Improvement	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).	week 4	No
Secondary	Clinical Global Impressions - Improvement	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).	week 8	No
Secondary	Clinical Global Impressions - Improvement	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).	week 12	No
Secondary	Clinical Global Impressions - Improvement	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).	week 16	No
Secondary	Clinical Global Impressions - Improvement	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).	week 20	No
Secondary	Clinical Global Impressions - Improvement	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).	week 24	No
Secondary	Patient Global Impression - Improvement	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).	week 1	No
Secondary	Patient Global Impression - Improvement	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).	week 2	No
Secondary	Patient Global Impression - Improvement	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).	week 3	No
Secondary	Patient Global Impression - Improvement	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).	week 4	No
Secondary	Patient Global Impression - Improvement	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).	week 8	No
Secondary	Patient Global Impression - Improvement	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).	week 12	No
Secondary	Patient Global Impression - Improvement	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).	week 16	No
Secondary	Patient Global Impression - Improvement	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).	week 20	No
Secondary	Patient Global Impression - Improvement	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).	week 24	No
Secondary	Frequency of Patients With Possible Clinically Significant Abnormalities for Laboratory Parameters	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)	Baseline and 24 weeks	No

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