A Study of the Effectiveness and Safety of Tetrabenazine MR in Pediatric Subjects With Tourette's Syndrome (TBZ-MR)

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by:
Valeant Pharmaceuticals International, Inc.
ClinicalTrials.gov Identifier:
NCT01133353
First received: May 24, 2010
Last updated: November 17, 2010
Last verified: November 2010
  Purpose

The purpose of this clinical trial is to study the therapeutic effect of tetrabenazine MR in children with Tourette's Syndrome, as measured by the improvement in total tic score of the Yale Global Tic Severity Scale (YGTSS).


Condition Intervention Phase
Tourette's Syndrome
Drug: Tetrabenazine MR
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Tetrabenazine MR in Subjects Aged 5 up to 17 Years With Tourette's Syndrome

Resource links provided by NLM:


Further study details as provided by Valeant Pharmaceuticals International, Inc.:

Primary Outcome Measures:
  • Improvement in total tic score as measured by the Yale Global Tic Severity Score (YGTSS) [ Time Frame: Days 0 to 84 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate the safety and tolerability of tetrabenazine using cognitive measures [ Time Frame: Days 0 and 84 ] [ Designated as safety issue: Yes ]
  • To evaluate the safety and tolerability of tetrabenazine using an assessment of depression [ Time Frame: Days 0 to 84 ] [ Designated as safety issue: Yes ]
  • To evaluate the safety and tolerability of tetrabenazine using an assessment of suicidality [ Time Frame: Days 0 to 91 ] [ Designated as safety issue: Yes ]
  • To explore the therapeutic effects of tetrabenazine using the full YGTSS [ Time Frame: Days 0 to 84 ] [ Designated as safety issue: No ]
  • To explore the therapeutic effects of tetrabenazine using the Patient Global Impression of Change scale (PGI-C) [ Time Frame: Days 0 to 84 ] [ Designated as safety issue: No ]
  • To explore the therapeutic effects of tetrabenazine using the Clinical Global Impression of Severity scale (CGI-S) [ Time Frame: Days 0 to 84 ] [ Designated as safety issue: No ]

Estimated Enrollment: 160
Study Start Date: March 2011
Estimated Study Completion Date: December 2011
Estimated Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tetrabenazine MR Drug: Tetrabenazine MR
Modified-Release (MR) tablets containing 15 mg or 30 mg tetrabenazine, dose-escalating up to a maximum of 150 mg depending on weight, once per day for 12 weeks
Placebo Comparator: Placebo Drug: Placebo
1 to 5 tablets once per day depending on weight for 12 weeks

Detailed Description:

Tourette's Syndrome (TS) is typically diagnosed in early childhood (6-7 years) or before the age of 21 years and is characterized by chronic, intermittent motor and phonic tics. There is a body of evidence, mostly from the clinical experience data, suggesting the efficacy of tetrabenazine in TS patients with tics, including patients who were unresponsive to other treatment options. These publications consistently report the usefulness of tetrabenazine as an alternative to conventional neuroleptics for the treatment of TS.

  Eligibility

Ages Eligible for Study:   5 Years to 16 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Subjects must meet all of the following criteria:

  1. Children aged 5 to up to 17 years
  2. Subjects must be capable of providing informed consent or assent, if applicable, and parents/legal guardian must be capable of providing informed consent/permission and complying with study procedures
  3. Subject and parents/legal guardian must be able to communicate effectively with Investigator and study coordinator
  4. Diagnosed with Tourette's Syndrome, according to DSM-IV-TR and using K-SADS-PL to aid diagnosis, and requiring drug therapy
  5. Total tic score ≥ 22 as measured by YGTSS at screening and baseline
  6. Total body weight ≥ 15 kg (33 lbs.)
  7. Tics are causing distress or impairment, as determined by parent/legal guardian or subject and by the Investigator, despite current treatment regimen
  8. Able to swallow whole tablets without difficulty
  9. Non-pregnant status:

    • All female subjects must be non-pregnant (as demonstrated by negative serum β-HCG test), non-breastfeeding, and must avoid pregnancy from at least 10 days before signing the informed consent/assent and up until 1 month after the end of the study by abstaining from sexual activity or using two (2) medically acceptable methods of contraception, such as: a non-hormonal IUD with spermicide, female condom with spermicide, contraceptive sponge with spermicide, an intravaginal system, diaphragm with spermicide, cervical cap with spermicide, a male sexual partner who agrees to use a male condom with spermicide, a sterile sexual partner.
    • Male subjects must abstain from sexual activity from the time they sign the informed consent/assent and up until 1 month after the end of the study or use a condom with spermicide.
    • For all females of child bearing potential, a serum pregnancy test result must be negative at Screening and urine pregnancy test must be negative at Baseline

Exclusion Criteria:

Subjects are not eligible if any of the following criteria are met:

  1. Subjects with history or current major depressive disorder
  2. Prior treatment with > 7 doses of tetrabenazine
  3. Prior treatment with reserpine
  4. Subjects with impaired renal function (defined as having a creatinine level of ≥ 1.5 times the upper limit of age-appropriate normal value)
  5. Subjects with current or any history of suicidal ideation
  6. Participation in an investigational medication trial within the 3 months prior to the Screening visit, except for study BVF-018-102
  7. Use of Botox® (botulinum toxin) within the 4 months prior to the Screening visit
  8. Immediate families of site Investigators or sponsor employees
  9. Excluding conditions related directly to the disease under study, subject has a history or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or oncologic or any other condition that, in the opinion of the Investigator, would jeopardize the safety of the subject or the validity of the study results.
  10. Subjects with clinically important thyroid dysfunction requiring medication
  11. Subjects with impaired hepatic function (defined as having SGOT/SGPT levels ≥ 1.5 times the upper limit of age-appropriate normal values)
  12. Subjects with a Children's Depression Rating Scale-Revised (CDRS-R) total score of > 65
  13. Male subjects with QTc > 450 msec; female subjects with QTc > 470 msec based on Bazzett's correction formula
  14. Organic brain disease, for example, traumatic brain injury residua or toxic delirium
  15. Any subject at immediate risk of requiring hospitalization
  16. Physical examination, electrocardiography, or laboratory values that are clinically important in the opinion of the Investigator
  17. Autistic spectrum disorder
  18. Schizophrenia
  19. Other psychotic disorder
  20. Subjects with Bipolar I Disorder
  21. Subjects with one or more first-degree relatives with Bipolar I Disorder
  22. Subjects who are unable to complete a washout period of 4 weeks for fluoxetine and 3 weeks for MAOIs, respectively, prior to Baseline visit and who require fluoxetine and MAOIs during the Treatment Period
  23. Inability to washout of strong inhibitors or inducers of CYP2D6 within 7 days of the Baseline visit
  24. Positive findings on urine drug screen at the Screening Visit
  25. Allergies to tetrabenazine or its excipients
  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.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Diane Anderson, Biovail Laboratories International SRL
ClinicalTrials.gov Identifier: NCT01133353     History of Changes
Other Study ID Numbers: BVF-018-201
Study First Received: May 24, 2010
Last Updated: November 17, 2010
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Tourette Syndrome
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
Tetrabenazine
Adrenergic Uptake Inhibitors
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Neurotransmitter Uptake Inhibitors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 18, 2014