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
  Purpose

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 Intervention 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 Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open Label Extension Study With Pramipexole (PPX) in Children With Tourette Syndrome

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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 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 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)


Enrollment: 45
Study Start Date: May 2008
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   6 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00681863

Locations
United States, Florida
248.642.0026 Boehringer Ingelheim Investigational Site
Bradenton, Florida, United States
248.642.0025 Boehringer Ingelheim Investigational Site
Tampa, Florida, United States
United States, Georgia
248.642.0006 Boehringer Ingelheim Investigational Site
Columbus, Georgia, United States
United States, Massachusetts
248.642.0005 Boehringer Ingelheim Investigational Site
Cambridge, Massachusetts, United States
United States, New York
248.642.0003 Boehringer Ingelheim Investigational Site
Manhasset, New York, United States
248.642.0018 Boehringer Ingelheim Investigational Site
New York, New York, United States
248.642.0009 Boehringer Ingelheim Investigational Site
New York, New York, United States
248.642.0013 Boehringer Ingelheim Investigational Site
Orangeburg, New York, United States
United States, Oklahoma
248.642.0029 Boehringer Ingelheim Investigational Site
Oklahoma City, Oklahoma, United States
United States, Rhode Island
248.642.0010 Boehringer Ingelheim Investigational Site
Providence, Rhode Island, United States
United States, Tennessee
248.642.0030 Boehringer Ingelheim Investigational Site
Memphis, Tennessee, United States
United States, Texas
248.642.0008 Boehringer Ingelheim Investigational Site
Houston, Texas, United States
United States, Virginia
248.642.0023 Boehringer Ingelheim Investigational Site
Norfolk, Virginia, United States
Germany
248.642.49004 Boehringer Ingelheim Investigational Site
Ulm, Germany
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00681863     History of Changes
Other Study ID Numbers: 248.642, 2008-000342-32
Study First Received: May 19, 2008
Results First Received: October 13, 2010
Last Updated: May 7, 2014
Health Authority: Brazil: Comitê Nacional de Ética em Pesquisa Clínica - CONEP
Germany: BfArM-Federal Authorities for Drugs and Medical Devices
United States: Food and Drug Administration

Additional relevant MeSH terms:
Syndrome
Tourette Syndrome
Disease
Pathologic Processes
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tic Disorders
Movement Disorders
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Mental Disorders Diagnosed in Childhood
Mental Disorders
Pramipexole
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Dopamine Agonists
Dopamine Agents
Neurotransmitter Agents

ClinicalTrials.gov processed this record on September 18, 2014