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).

Study Overview

• Status: Terminated
• Conditions: Tourette Syndrome
• Intervention / Treatment: Drug: pramipexole 0.0625 mg BID; Drug: pramipexole 0.0625 mg QD; Drug: pramipexole 0.125 mg BID; Drug: pramipexole 0.125 mg TID; Drug: pramipexole 0.25 mg BID

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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)
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: May 19, 2008
• First Submitted That Met QC Criteria: May 20, 2008
• First Posted (Estimate): May 21, 2008

Study Record Updates

• Last Update Posted (Estimate): May 23, 2014
• Last Update Submitted That Met QC Criteria: May 7, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Disease; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Neurodevelopmental Disorders; Tic Disorders; Syndrome; Tourette Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Protective Agents; Dopamine Agonists; Dopamine Agents; Antioxidants; Antiparkinson Agents; Anti-Dyskinesia Agents; Pramipexole
• Other Study ID Numbers: 248.642; 2008-000342-32 (EudraCT Number: EudraCT)