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

Phase 3TerminatedNCT00681863

Boehringer Ingelheim45 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Tourette Syndrome

Interventions

pramipexole 0.125 mg BIDDRUG

titrated dose for those patients whose symptoms were not controlled on the 0.0625 mg BID dose

pramipexole 0.0625 mg QDDRUG

dose down titrated for those patients unable to tolerate the 0.0625 mg BID dosing

pramipexole 0.125 mg TIDDRUG

titrated up for those patients whose symptoms were not adequately controlled on 0.125 mg BID dose

Eligibility

Sex: ALLMin age: 6 YearsMax age: 17 Years

Medical Language ↔ Plain English

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.

Locations (14)

248.642.0026 Boehringer Ingelheim Investigational Site

Bradenton, Florida, United States

248.642.0025 Boehringer Ingelheim Investigational Site

Tampa, Florida, United States

Outcomes

Primary Outcomes

Patients With Adverse Events Leading to Discontinuation of Trial Drug

Number of patients with Adverse Events leading to discontinuation of trial drug

Time frame: 24 Weeks

Secondary Outcomes

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.

Time frame: 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).

Time frame: 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.

Time frame: 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.

Time frame: 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.

Data from ClinicalTrials.gov

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titrated for those patients whose symptoms were not adequately controlled on 0.125 mg TID dose

pramipexole 0.0625 mg BIDDRUG

0.0625 mg BID given for first 4 wks of treatment

248.642.0006 Boehringer Ingelheim Investigational Site

Columbus, Georgia, United States

248.642.0005 Boehringer Ingelheim Investigational Site

Cambridge, Massachusetts, United States

248.642.0003 Boehringer Ingelheim Investigational Site

Manhasset, New York, United States

248.642.0009 Boehringer Ingelheim Investigational Site

New York, New York, United States

248.642.0018 Boehringer Ingelheim Investigational Site

New York, New York, United States

248.642.0013 Boehringer Ingelheim Investigational Site

Orangeburg, New York, United States

248.642.0029 Boehringer Ingelheim Investigational Site

Oklahoma City, Oklahoma, United States

248.642.0010 Boehringer Ingelheim Investigational Site

Providence, Rhode Island, United States

...and 4 more locations

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: week 1

Patient Global Impression - Improvement

Time frame: week 2

Patient Global Impression - Improvement

Time frame: week 3

Patient Global Impression - Improvement

Time frame: week 4

Patient Global Impression - Improvement

Time frame: week 8

Patient Global Impression - Improvement

Time frame: week 12

Patient Global Impression - Improvement

Time frame: week 16

Patient Global Impression - Improvement

Time frame: week 20

Patient Global Impression - Improvement

Time frame: 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)

Time frame: Baseline and 24 weeks