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

Sponsor:	Boehringer Ingelheim Pharmaceuticals
Information provided by:	Boehringer Ingelheim Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00558467

Purpose

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.

Condition	Intervention	Phase
Tourette Syndrome	Drug: pramipexole IR Drug: Placebo	Phase II

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Primary Purpose: Treatment
Official Title:	A Randomized, Double-blind, Placebo-controlled, Flexible Dose Study to Evaluate Efficacy and Safety of Pramipexole IR (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.

Resource links provided by NLM:

Genetics Home Reference related topics: familial paroxysmal nonkinesigenic dyskinesia Tourette syndrome

MedlinePlus related topics: Tourette Syndrome

Drug Information available for: Pramipexol Pramipexole dihydrochloride

U.S. FDA Resources

Further study details as provided by Boehringer Ingelheim Pharmaceuticals:

Primary Outcome Measures:

Mean Change From Baseline in Total Tic Score of the Yale Global Tic Severity Scale [ Time Frame: baseline 6 weeks ] [ 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.

Analysis was adjusted for baseline total tic score and age as linear covariates.

Secondary Outcome Measures:

Mean Change From Baseline in Total Tic Score of the Yale Global Tic Severity Scale at Week 1 [ Time Frame: baseline 1 week ] [ 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 of the Yale Global Tic Severity Scale at Week 2 [ Time Frame: baseline and 2 weeks ] [ 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 of the Yale Global Tic Severity Scale at Week 3 [ Time Frame: baseline and 3 weeks ] [ 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 of the Yale Global Tic Severity Scale at Week 4 [ Time Frame: baseline and 4 weeks ] [ 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 Due to Motor and Phonic Tics at Week 6 [ Time Frame: baseline and 6 weeks ] [ 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 Due to Motor and Phonic Tics at Week 1 [ Time Frame: baseline 1 week ] [ 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 Due to Motor and Phonic Tics at Week 2 [ Time Frame: baseline and 2 weeks ] [ 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 Due to Motor and Phonic Tics at Week 3 [ Time Frame: baseline and 3 weeks ] [ 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 Due to Motor and Phonic Tics at Week 4 [ Time Frame: baseline 4 weeks ] [ 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 - Improvement at 1 Week [ Time Frame: baseline and Week 1 ] [ 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 - Improvement at Week 2 [ Time Frame: baseline and Week 2 ] [ 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 - Improvement at Week 3 [ Time Frame: baseline and Week 3 ] [ 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 - Improvement at Week 4 [ Time Frame: baseline and Week 4 ] [ 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 - Improvement at Week 6 [ Time Frame: baseline and Week 6 ] [ 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 at Week 1 [ Time Frame: baseline and Week 1 ] [ Designated as safety issue: No ]
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.
Clinical Global Impressions - Severity of Illness at Week 2 [ Time Frame: baseline and Week 2 ] [ Designated as safety issue: No ]
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.
Clinical Global Impressions - Severity of Illness at Week 3 [ Time Frame: baseline and Week 3 ] [ Designated as safety issue: No ]
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.
Clinical Global Impressions - Severity of Illness at Week 4 [ Time Frame: baseline and Week 4 ] [ Designated as safety issue: No ]
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.
Clinical Global Impressions - Severity of Illness at Week 6 [ Time Frame: baseline and Week 6 ] [ Designated as safety issue: No ]
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.
Patient Global Impression at Week 1 [ Time Frame: baseline and 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 at Week 2 [ Time Frame: baseline and 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 at Week 3 [ Time Frame: baseline and 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 at Week 4 [ Time Frame: baseline and 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 at Week 6 [ Time Frame: baseline and Week 6 ] [ 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).

Enrollment:	63
Study Start Date:	January 2008
Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Pramipexole	Drug: pramipexole IR
Placebo Comparator: Placebo	Drug: Placebo

Eligibility

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

Criteria

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 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.

United States, Florida
248.644.0026 Boehringer Ingelheim Investigational Site
Bradenton, Florida, United States
248.644.0025 Boehringer Ingelheim Investigational Site
Tampa, Florida, United States
United States, Georgia
248.644.0006 Boehringer Ingelheim Investigational Site
Columbus, Georgia, United States
United States, Illinois
248.644.0012 Boehringer Ingelheim Investigational Site
Chicago, Illinois, United States
United States, Massachusetts
248.644.0005 Boehringer Ingelheim Investigational Site
Cambridge, Massachusetts, United States
United States, New York
248.644.0003 Boehringer Ingelheim Investigational Site
Manhasset, New York, United States
248.644.0009 Boehringer Ingelheim Investigational Site
New York, New York, United States
248.644.0018 Boehringer Ingelheim Investigational Site
New York, New York, United States
248.644.0013 Boehringer Ingelheim Investigational Site
Orangeburg, New York, United States
United States, Oklahoma
248.644.0029 Boehringer Ingelheim Investigational Site
Oklahoma City, Oklahoma, United States
United States, Rhode Island
248.644.0010 Boehringer Ingelheim Investigational Site
Providence, Rhode Island, United States
United States, Tennessee
248.644.0030 Boehringer Ingelheim Investigational Site
Memphis, Tennessee, United States
United States, Texas
248.644.0008 Boehringer Ingelheim Investigational Site
Houston, Texas, United States
United States, Virginia
248.644.0023 Boehringer Ingelheim Investigational Site
Norfolk, Virginia, United States
Germany
248.644.49001 Boehringer Ingelheim Investigational Site
Hannover, Germany
248.644.49004 Boehringer Ingelheim Investigational Site
Ulm, Germany

Responsible Party:	Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
ClinicalTrials.gov Identifier:	NCT00558467 History of Changes
Other Study ID Numbers:	248.644
Study First Received:	November 14, 2007
Results First Received:	June 18, 2010
Last Updated:	July 4, 2011
Health Authority:	Germany: BfArM-Federal Authorities for Drugs and Medical Devices; United States: Food and Drug Administration