Pramipexole Pilot Phase II Study in Children and Adolescents With Tourette Disorder According to DSM-IV Criteria

Study Overview
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Brief Summary
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A randomized, double-blind, placebo-controlled, flexible dose study to evaluate efficacy and safety of Pramipexole versus placebo for 6 weeks in children (age 6-17) diagnosed with Tourette Disorder according to DSM IV criteria. The primary efficacy measure will be the Total Tic Score (TTS) of the Yale Global Tic Severity Scale (YGTSS) at 6 weeks.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Flexible Dose Study to Evaluate Efficacy and Safety of Pramipexole Immediate Release (0.125-0.5mg/Day) Versus Placebo for 6 Weeks in Children and Adolescents (Age 6-17 Inclusive) Diagnosed With Tourette Disorder According to DSM IV Criteria.

Conditions
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Tourette Syndrome

Intervention / Treatment
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* Drug: pramipexole immediate release (IR)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male of female patients 6-17 yrs. Written informed consent. Diagnosed with Tourette's Disorder with a > or equal to 22 on the Total Tic Score at baseline. Diagnosed with Tourette's Disorder when administering the Diagnostic Interview Schedule for Children. Having at least 1 tic/day. Women of childbearing age must have a negative serum pregnancy test at screening and must use a medically accepted contraceptive method. Either a newly diagnosed patient or a patient diagnosed with Tourette's Disorder who can safely discontinue treatment. Having a body weight of > or equal to 20 kg (44 lbs). Exclusion Criteria: Any women of childbearing age having a positive serum pregnancy test at screening. Patients who have clinically significant renal disease or serum creatinine greater than 1.0 mg/dL at screening. Lab results at screening: hemoglobin below lower limit of normal which is determined to be clinically significant; Thyroid Stimulating Hormone (TSH), triiodothyronine (T3) or thyroxine (T4) clinically significant; clinically significant abnormalities in labs. Other clinically significant metabolic-endocrine, hematological, gastrointestinal disease, pulmonary disease which would preclude the patient from participating in this study. History of Schizophrenia or any psychotic disorder, history of mental disorders or any present Axis I psychiatric disorder according to Diagnostic and Statistic Manual of Mental Disorders Fourth Edition (DSM-IV) requiring any medical therapy except for patients with a diagnosis of attention deficit hyperactivity disorder (ADHD) or obsessive-compulsive disorder (OCD) who are not on therapy. History of/or clinical signs of epilepsy or seizures other than fever related seizures in early childhood. History of/or clinical signs of any malignant neoplasm. Allergic response to pramipexole. Had previous treatment with dopamine agonists other than pramipexole within 14 days prior to baseline visit. Had any other medical treatment for Tourette's Disorder besides the study medication within 28 days prior to baseline visit. Had withdrawal symptoms of any medication at screening or at the baseline visit. Having a Kaufman Brief Intelligence Test (KBIT IQ) score <70 at screening. Having a children's Yale-Brown obsessive-compulsive scale (CY-BOCS) score of >15 at baseline. Patients who meet criteria for Restless Legs Syndrome and or Periodic Limb Movement disorder. Patients with severe asthma. Patients that have initiated psychotherapy for Tourette's Disorder, OCD or ADHD within 3 mths of starting the trial. Patients receiving psychological, cognitive and/or behavioral treatments greater than 3 mths prior to start of trial for Tourette's Disorder, OCD, and/or ADHD who will have changes in treatment plan.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Pramipexole<br> | Drug: pramipexole immediate release (IR)<br> <br> |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Total Tic Score 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. Analysis was adjusted for baseline total tic score and age as linear covariates. | baseline 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Total Tic Score of the Yale Global Tic Severity Scale at 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 | baseline 1 week | 
| Mean Change From Baseline in Total Tic Score of the Yale Global Tic Severity Scale at 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 | baseline and 2 weeks | 
| Mean Change From Baseline in Total Tic Score of the Yale Global Tic Severity Scale at 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 | baseline and 3 weeks | 
| Mean Change From Baseline in Total Tic Score of the Yale Global Tic Severity Scale at 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 | baseline and 4 weeks | 
| Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale Due to Motor and Phonic Tics at Week 6 | 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 6 weeks | 
| Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale Due to Motor and Phonic Tics at 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) | baseline 1 week | 
| Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale Due to Motor and Phonic Tics at 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) | baseline and 2 weeks | 
| Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale Due to Motor and Phonic Tics at 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) | baseline and 3 weeks | 
| Mean Change From Baseline in Total Score of the Yale Global Tic Severity Scale Due to Motor and Phonic Tics at 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) | baseline 4 weeks | 
| Clinical Global Impressions - Improvement at 1 Week | 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. | baseline and Week 1 | 
| Clinical Global Impressions - Improvement at Week 2 | 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. | baseline and Week 2 | 
| Clinical Global Impressions - Improvement at Week 3 | 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. | baseline and Week 3 | 
| Clinical Global Impressions - Improvement at Week 4 | 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. | baseline and Week 4 | 
| Clinical Global Impressions - Improvement at Week 6 | 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. | baseline and Week 6 | 
| Clinical Global Impressions - Severity of Illness at Week 1 | Assessment of the overall severity of illness on a scale ranging from 1 (not at all ill) to 7 (the most extremely ill patients). Improved, Unchanged and Worsened responses correspond to changes from baseline of: -2 or less, -1 to +1, and 2 or greater. | baseline and Week 1 | 
| Clinical Global Impressions - Severity of Illness at Week 2 | Assessment of the overall severity of illness on a scale ranging from 1 (not at all ill) to 7 (the most extremely ill patients). Improved, Unchanged and Worsened responses correspond to changes from baseline of: -2 or less, -1 to +1, and 2 or greater. | baseline and Week 2 | 
| Clinical Global Impressions - Severity of Illness at Week 3 | Assessment of the overall severity of illness on a scale ranging from 1 (not at all ill) to 7 (the most extremely ill patients). Improved, Unchanged and Worsened responses correspond to changes from baseline of: -2 or less, -1 to +1, and 2 or greater. | baseline and Week 3 | 
| Clinical Global Impressions - Severity of Illness at Week 4 | Assessment of the overall severity of illness on a scale ranging from 1 (not at all ill) to 7 (the most extremely ill patients). Improved, Unchanged and Worsened responses correspond to changes from baseline of: -2 or less, -1 to +1, and 2 or greater. | baseline and Week 4 | 
| Clinical Global Impressions - Severity of Illness at Week 6 | Assessment of the overall severity of illness on a scale ranging from 1 (not at all ill) to 7 (the most extremely ill patients). Improved, Unchanged and Worsened responses correspond to changes from baseline of: -2 or less, -1 to +1, and 2 or greater. | baseline and Week 6 | 
| Patient Global Impression at 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). | baseline and Week 1 | 
| Patient Global Impression at 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). | baseline and Week 2 | 
| Patient Global Impression at 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). | baseline and Week 3 | 
| Patient Global Impression at 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). | baseline and Week 4 | 
| Patient Global Impression at Week 6 | 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). | baseline and Week 6 | 
| Clinically Significant Abnormalities in Vital Signs (Orthostatic Reaction and Pulse Rate), and Serum Chemistry. |  | baseline and Week 6 |