Safety, Tolerability, Pharmacokinetic, and Efficacy Study of AZD5213 in Adolescents With Tourette's Disorder

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by AstraZeneca
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01904773
First received: July 18, 2013
Last updated: March 28, 2014
Last verified: March 2014
  Purpose

This is a two-part, randomized, multi-center, blinded study in adolescents with Tourette's Disorder. There will be an up to 21-day screening period in which subject eligiblity willl be determined. In Part 1 of the study, the safety, tolerability and pharmacokinetics of AZD5213 will be assessed during a 1- week period.

In Part 2 of the study, the safety, tolerability, and preliminary efficacy of two doses (depending on tolerability in Part 1 of the study) of AZD5213 and placebo will be assessed through six consecutive four-week crossover periods. Each subject will receive both AZD 5213 and placebo. A follow-up vist will take place at 14 (±) 7 days following the last dose of study drug.


Condition Intervention Phase
Tourette Syndrome
Drug: AZD5213 and placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A 6-month, Multicenter, Randomized, Safety, Tolerability, Pharmacokinetic, and Preliminary Efficacy Study of AZD5213 in Adolescents With Tourette's Disorder

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • The primary outcome variable is the Total Tic Severity Score (TTS) on the Yale Global Tic Severity Scale (YGTSS). [ Time Frame: From Day 9-Day 176 ] [ Designated as safety issue: No ]
    The TTS will be analyzed using a mixed linear model with "Subject" as a random main effect factor, "Period" as a fixed main effect factor with six levels and "Treatment" as a fixed main effect factor with three levels. In the main (primary) analysis model, there will be no interactive effects.There will be two primary contrasts of equal interest: that comparing the high dose of AZD5213 and placebo, and that comparing the low dose of AZD5213 and placebo. The Bonferroni-Holm procedure will be used to control a 5% error rate (two-sided) overall. In this manner, the smaller of the two unadjusted P-values will be compared to the 2.5% level (two-sided), and, if that is significant, the remaining P-value will be compared to 5% (two-sided).

  • Determine Plasma Pharmacokinetic parameters for AZD5213 (and, if appropriate metabolites) [ Time Frame: From Day 1-8 ] [ Designated as safety issue: No ]
    Plasma AZD5213 (and, if appropriate, metabolite) concentrations and noncompartmental pharmacokinetics will be summarized descriptively.


Secondary Outcome Measures:
  • Incidence and Severity of Treatment Emergent Adverse Events [ Time Frame: Day 1-8 for Part 1; Day 9-176 for Part 2 ] [ Designated as safety issue: Yes ]
    incidence and severity of treatment-emergent adverse events (TEAEs) will be summarized by treatment separately for Part 1 and Part 2.

  • Vital Signs [ Time Frame: Day 1-8 for Part 1;Day 9-176 for Part 2 ] [ Designated as safety issue: Yes ]
    Vital signs include blood pressure, temperature and pulse. Vital signs will be summarized with descriptive statistics, by treatment, separately for Part 1 and Part 2.

  • 12-Lead Electrocardiogram [ Time Frame: Day 1-8 for Part 1;Day 9-176 for Part 2 ] [ Designated as safety issue: Yes ]
    Heart Rate, QRS duration, PR, QT and QTc interval will be summarized with descriptive statistics, by treatment, separately for Part 1 and Part 2

  • Clinical Laboratory Evaluations [ Time Frame: Day 1-8 for Part 1;Day 9-176 for Part 2 ] [ Designated as safety issue: Yes ]
    Clinical Laboratory Evaluations will be summarized with descriptive statistics, by treatment, separately for Part 1 and Part 2

  • MOS-Sleep Scale [ Time Frame: Day 1-8 for Part 1;Day 9-176 for Part 2 ] [ Designated as safety issue: Yes ]
    MOS-Sleep Scale will be summarized with descriptive statistics, by treatment, separately for Part 1 and Part 2

  • CDRS-R [ Time Frame: Day 1-8 for Part 1;Day 9-176 for Part 2 ] [ Designated as safety issue: Yes ]
    CDRS-R will be summarized with descriptive statistics, by treatment, separately for Part 1 and Part 2

  • C-SSRS [ Time Frame: Day 1-8 for Part 1;Day 9-176 for Part 2 ] [ Designated as safety issue: Yes ]
    C-SSRS will be summarized with descriptive statistics, by treatment, separately for Part 1 and Part 2


Other Outcome Measures:
  • Exploratory analysis will be carried out to determine whether there is evidence that some subjects respond differently than others [ Time Frame: From Day 9-Day 176 ] [ Designated as safety issue: No ]
    This will be done by augmenting the Bonferroni-Holm model by fitting a random subject-by-treatment interaction term. The equivalent mixed linear model used for the primary analysis of the TTS will be used to analyze the YGTSS total score, the YGTSS motor tic severity score, the YGTSS vocal tic severity score, the YGTSS impairment score, the PUTS, the CY-BOCS, and the CGI-TS (Severity). These analyses will be carried out in an exploratory manner and supplemented by applying the method of basic estimators as described in Senn (2002).


Estimated Enrollment: 29
Study Start Date: August 2013
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Drug: AZD5213 and placebo
low dose AZD5213 capsules; high dose AZD5213 capsules; placebo capsules
Experimental: low dose AZD5213 Drug: AZD5213 and placebo
low dose AZD5213 capsules; high dose AZD5213 capsules; placebo capsules
Experimental: high dose AZD5213 Drug: AZD5213 and placebo
low dose AZD5213 capsules; high dose AZD5213 capsules; placebo capsules

Detailed Description:

This is a multicenter, randomized, two-part study of AZD5213 in adolescents (ages 12-17 years) with TD.

In Part 1 of the study, following an up to 21-day screening period, on Day 1, after baseline procedures are performed, eligible subjects will receive a single, low dose of AZD5213, in-clinic.

After study drug dosing on Day 1, safety and tolerability will be assessed in-clinic, and blood samples will be taken for pharmacokinetic (PK) analysis. On Days 2, 3, 4, 5, 6 and 7 subjects will take study drug, and will be contacted via telephone and adverse events and concomitant medications will be assessed. On Day 8, safety, tolerability, and blood sampling for PK analysis (predose and 2-4 hours post-dose) will be performed in-clinic. Part 2 of the study will consist of six consecutive crossover periods. In Part 2 of the study, each study drug will be administered in two 4-week periods (six treatment periods, total). Each study drug will be received in one of Periods 1-3, and again in one of Periods 4-6. Approximately 24 subjects will receive study drug in Part 1 of this study in order to complete approximately 18 subjects in Part 2.

  Eligibility

Ages Eligible for Study:   12 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female, between the ages of ≥ 12 and < 18 years at baseline (Day 1).
  2. Meets Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for TD, as assessed by the Kiddie-SADS (Schedule for Affective Disorders and Schizophrenia)-Present and Lifetime Version (K-SADS-PL) Tic Disorder Supplement and clinical interview.
  3. Yale Global Tic Severity Scale (YGTSS) Total Tic Severity Score (TTS) ≥ 20 at Screen and baseline (Day 1).
  4. Symptoms of TD must impair school, occupational, and/or social function.
  5. Written informed assent or consent provided by the subject, and written informed consent provided by the parent(s)/guardians(s), as appropriate per the IRB/EC. 6. Weight ≥ 40 kg at the screening and baseline (Day 1) visits.

7. In the opinion of the investigator, the subject and designated guardian(s) and/or parent(s) must be considered likely to comply with the study protocol and to have a high probability of completing the study.

Exclusion Criteria:

Subjects should not enter the study if any of the following exclusion criteria are fulfilled:

  1. Prior participation in any AZD5213 study.
  2. Acute suicidality as evidenced by answering "yes" for question #4 or question #5 on the Columbia-Suicide Severity Rating Scale (C-SSRS), indicating active suicidal ideation with any intent to act, at Screen or baseline (Day 1).
  3. Pregnant or breast-feeding females.
  4. History of seizure disorder other than a single childhood febrile seizure.
  5. Presence of any psychiatric or neurologic disorder or symptom, if, in the judgment of the investigator, the psychiatric or neurologic disorder or symptom is likely to confound interpretation of drug effect or affect the subject's ability to complete the study. 6. Any clinically important abnormality as determined by the investigator at Screen or baseline (Day 1) in physical or neurologic examination, vital sign, ECG, or clinical laboratory test results that could be detrimental to the subject or could affect the subject's ability to complete the study.

7. History or presence of any clinically important medical condition that, in the judgement of the investigator, is likely to deteriorate, could be detrimental to the subject, or could affect the subject's ability to complete the study.

8. History or presence of a clinically important sleep disorder.

  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.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01904773

Contacts
Contact: Clinical Trial Transparency ClinicalTrialTransparency@astrazeneca.com
Contact: Anne Macek, MD 610-296-1574 anne.macek@theoremclinical.com

Locations
United States, California
Research Site Recruiting
Orange, California, United States
United States, Florida
Research Site Recruiting
St. Petersburg, Florida, United States
United States, New Jersey
Research Site Recruiting
Marlton, New Jersey, United States
Research Site Recruiting
Summit, New Jersey, United States
United States, New York
Research Site Recruiting
Manhasset, New York, United States
Research Site Recruiting
New York, New York, United States
United States, Ohio
Research Site Recruiting
Cincinnati, Ohio, United States
United States, Utah
Research Site Recruiting
Orem, Utah, United States
Research Site Recruiting
Salt Lake City, Utah, United States
Sponsors and Collaborators
AstraZeneca
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01904773     History of Changes
Other Study ID Numbers: D3032C00001
Study First Received: July 18, 2013
Last Updated: March 28, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by AstraZeneca:
Combined Multiple Motor and Vocal Tic Disorder; Tourette Disorder; Gilles de la Tourette Syndrome; Tourette Disease

Additional relevant MeSH terms:
Syndrome
Tourette Syndrome
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Disease
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Mental Disorders
Mental Disorders Diagnosed in Childhood
Movement Disorders
Nervous System Diseases
Neurodegenerative Diseases
Pathologic Processes
Tic Disorders

ClinicalTrials.gov processed this record on October 20, 2014