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

This study has been terminated.
(Terminated for slow enrollment.)
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00681863
First received: May 19, 2008
Last updated: May 7, 2014
Last verified: May 2014

May 19, 2008
May 7, 2014
May 2008
October 2009   (final data collection date for primary outcome measure)
Patients With Adverse Events Leading to Discontinuation of Trial Drug [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
Number of patients with Adverse Events leading to discontinuation of trial drug
Incidence of adverse events, proportion of withdrawals due to drug related adverse events, and assessment of the following scales: CYBOCS, CBCL, ADHD, CDI S, MASC. [ Time Frame: 24 weeks ]
Complete list of historical versions of study NCT00681863 on ClinicalTrials.gov Archive Site
  • Mean Change From Baseline in Total Tic Score (TTS) of the Yale Global Tic Severity Scale [ Time Frame: baseline and week 24 ] [ Designated as safety issue: No ]
    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.
  • Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale [ Time Frame: baseline and Week 24 (end of treatment visit) ] [ Designated as safety issue: No ]
    Total Score is a rating of the overall impairment due to motor and phonic tics. The scale ranges from 0 (None) to 50 (Severe).
  • Mean Change From Baseline in Total Tic Score (TTS) of the Yale Global Tic Severity Scale [ Time Frame: baseline and Week 1 ] [ Designated as safety issue: No ]
    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.
  • Mean Change From Baseline in Total Tic Score (TTS) of the Yale Global Tic Severity Scale [ Time Frame: baseline and Week 2 ] [ Designated as safety issue: No ]
    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.
  • Mean Change From Baseline in Total Tic Score (TTS) of the Yale Global Tic Severity Scale [ Time Frame: baseline and Week 3 ] [ Designated as safety issue: No ]
    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.
  • Mean Change From Baseline in Total Tic Score (TTS) of the Yale Global Tic Severity Scale [ Time Frame: baseline and week 4 ] [ Designated as safety issue: No ]
    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.
  • Mean Change From Baseline in Total Tic Score (TTS) of the Yale Global Tic Severity Scale [ Time Frame: baseline and Week 8 ] [ Designated as safety issue: No ]
    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.
  • Mean Change From Baseline in Total Tic Score (TTS) of the Yale Global Tic Severity Scale [ Time Frame: baseline and Week 12 ] [ Designated as safety issue: No ]
    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.
  • Mean Change From Baseline in Total Tic Score (TTS) of the Yale Global Tic Severity Scale [ Time Frame: baseline and Week 16 ] [ Designated as safety issue: No ]
    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.
  • Mean Change From Baseline in Total Tic Score (TTS) of the Yale Global Tic Severity Scale [ Time Frame: baseline and Week 20 ] [ Designated as safety issue: No ]
    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.
  • Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale [ Time Frame: baseline and Week 1 ] [ Designated as safety issue: No ]
    Total Score is a rating of the overall impairment due to motor and phonic tics. The scale ranges from 0 (None) to 50 (Severe).
  • Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale [ Time Frame: baseline and Week 2 ] [ Designated as safety issue: No ]
    Total Score is a rating of the overall impairment due to motor and phonic tics. The scale ranges from 0 (None) to 50 (Severe).
  • Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale [ Time Frame: baseline and Week 3 ] [ Designated as safety issue: No ]
    Total Score is a rating of the overall impairment due to motor and phonic tics. The scale ranges from 0 (None) to 50 (Severe).
  • Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale [ Time Frame: baseline and Week 4 ] [ Designated as safety issue: No ]
    Total Score is a rating of the overall impairment due to motor and phonic tics. The scale ranges from 0 (None) to 50 (Severe).
  • Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale [ Time Frame: baseline and Week 8 ] [ Designated as safety issue: No ]
    Total Score is a rating of the overall impairment due to motor and phonic tics. The scale ranges from 0 (None) to 50 (Severe).
  • Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale [ Time Frame: baseline and Week 12 ] [ Designated as safety issue: No ]
    Total Score is a rating of the overall impairment due to motor and phonic tics. The scale ranges from 0 (None) to 50 (Severe).
  • Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale [ Time Frame: baseline and Week 16 ] [ Designated as safety issue: No ]
    Total Score is a rating of the overall impairment due to motor and phonic tics. The scale ranges from 0 (None) to 50 (Severe).
  • Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale [ Time Frame: baseline and Week 20 ] [ Designated as safety issue: No ]
    Total Score is a rating of the overall impairment due to motor and phonic tics. The scale ranges from 0 (None) to 50 (Severe).
  • Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale [ Time Frame: baseline and Week 24 ] [ Designated as safety issue: No ]
    Total Score is a rating of the overall impairment due to motor and phonic tics. The scale ranges from 0 (None) to 50 (Severe).
  • Clinical Global Impressions - Severity of Illness [ Time Frame: week 24 ] [ Designated as safety issue: No ]
    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.
  • Clinical Global Impressions - Severity of Illness, Categorized [ Time Frame: week 24 ] [ Designated as safety issue: No ]

    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.

  • Clinical Global Impressions - Improvement [ Time Frame: week 1 ] [ Designated as safety issue: No ]
    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).
  • Clinical Global Impressions - Improvement [ Time Frame: week 2 ] [ Designated as safety issue: No ]
    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).
  • Clinical Global Impressions - Improvement [ Time Frame: week 3 ] [ Designated as safety issue: No ]
    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).
  • Clinical Global Impressions - Improvement [ Time Frame: week 4 ] [ Designated as safety issue: No ]
    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).
  • Clinical Global Impressions - Improvement [ Time Frame: week 8 ] [ Designated as safety issue: No ]
    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).
  • Clinical Global Impressions - Improvement [ Time Frame: week 12 ] [ Designated as safety issue: No ]
    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).
  • Clinical Global Impressions - Improvement [ Time Frame: week 16 ] [ Designated as safety issue: No ]
    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).
  • Clinical Global Impressions - Improvement [ Time Frame: week 20 ] [ Designated as safety issue: No ]
    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).
  • Clinical Global Impressions - Improvement [ Time Frame: week 24 ] [ Designated as safety issue: No ]
    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).
  • Patient Global Impression - Improvement [ Time Frame: week 1 ] [ Designated as safety issue: No ]
    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).
  • Patient Global Impression - Improvement [ Time Frame: week 2 ] [ Designated as safety issue: No ]
    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).
  • Patient Global Impression - Improvement [ Time Frame: week 3 ] [ Designated as safety issue: No ]
    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).
  • Patient Global Impression - Improvement [ Time Frame: week 4 ] [ Designated as safety issue: No ]
    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).
  • Patient Global Impression - Improvement [ Time Frame: week 8 ] [ Designated as safety issue: No ]
    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).
  • Patient Global Impression - Improvement [ Time Frame: week 12 ] [ Designated as safety issue: No ]
    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).
  • Patient Global Impression - Improvement [ Time Frame: week 16 ] [ Designated as safety issue: No ]
    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).
  • Patient Global Impression - Improvement [ Time Frame: week 20 ] [ Designated as safety issue: No ]
    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).
  • Patient Global Impression - Improvement [ Time Frame: week 24 ] [ Designated as safety issue: No ]
    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).
  • Frequency of Patients With Possible Clinically Significant Abnormalities for Laboratory Parameters [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
    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)
Change from baseline in the Total Tic Score (TTS) of the YGTSS, in the Total Score of the YGTSS and GCI S. Change from baseline in the TTS and in Total Score of the YGTSS, in PGCI and CGI at Weeks 1, 2, 3, 4, 8, 12, 16, 20 and 24. [ Time Frame: 24 weeks ]
Not Provided
Not Provided
 
Open-label Extension Study of Pramipexole in the Treatment of Children and Adolescents With Tourette Syndrome
Open Label Extension Study With Pramipexole (PPX) in Children With Tourette Syndrome

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).

Not Provided
Interventional
Phase 3
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Tourette Syndrome
  • Drug: pramipexole 0.125 mg BID
    titrated dose for those patients whose symptoms were not controlled on the 0.0625 mg BID dose
  • Drug: pramipexole 0.0625 mg QD
    dose down titrated for those patients unable to tolerate the 0.0625 mg BID dosing
  • Drug: pramipexole 0.125 mg TID
    titrated up for those patients whose symptoms were not adequately controlled on 0.125 mg BID dose
  • Drug: pramipexole 0.25 mg BID
    titrated for those patients whose symptoms were not adequately controlled on 0.125 mg TID dose
  • Drug: pramipexole 0.0625 mg BID
    0.0625 mg BID given for first 4 wks of 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)
    Intervention: Drug: pramipexole 0.0625 mg BID
  • Active Comparator: pramipexole 0.0625 mg QD (once daily)
    patients to receive one tablet of pramipexole 0.0625 mg QD
    Intervention: Drug: pramipexole 0.0625 mg QD
  • Active Comparator: pramipexole 0.125 mg BID
    patients to receive one tablet of pramipexole 0.125 mg BID
    Intervention: Drug: pramipexole 0.125 mg BID
  • Active Comparator: pramipexole 0.125 mg TID (three times daily)
    patients to receive one tablet of pramipexole 0.125 mg TID
    Intervention: Drug: pramipexole 0.125 mg TID
  • Active Comparator: pramipexole 0.25 mg BID
    patients to receive one tablet of pramipexole 0.25 mg BID
    Intervention: Drug: pramipexole 0.25 mg BID
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
45
Not Provided
October 2009   (final data collection date for primary outcome measure)

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.
Both
6 Years to 17 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Germany
 
NCT00681863
248.642, 2008-000342-32
Not Provided
Boehringer Ingelheim
Boehringer Ingelheim
Not Provided
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
Boehringer Ingelheim
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP