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

Tourette Syndrome Clinical Trial

Official title:

A 6-month, Multicenter, Randomized, Safety, Tolerability, Pharmacokinetic, and Preliminary Efficacy Study of AZD5213 in Adolescents With Tourette's Disorder

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01904773
• Other study ID #: D3032C00001
• Status: Completed
• Phase: Phase 2
• First received: July 18, 2013
• Last updated: September 22, 2016
• Start date: August 2013
• Est. completion date: February 2015

Study information

• Verified date: September 2016
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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 eligibility will 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 AZD5213 and placebo. A follow-up vist will take place at 14 (±) 7 days following the last dose of study drug.

Description:

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years to 17 Years

Eligibility

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 Tourette's Disorder, 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 Tourette's Disorder 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 Institutional Review Board/Ethics Committee. 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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Tourette Syndrome

Intervention

Drug:
• AZD5213 and placebo
low dose AZD5213 capsules; high dose AZD5213 capsules; placebo capsules

Locations

Country	Name	City	State
United States	Research Site	Cincinnati	Ohio
United States	Research Site	New York	New York
United States	Research Site	Orange	California
United States	Research Site	Orem	Utah
United States	Research Site	Salt Lake City	Utah
United States	Research Site	St. Petersburg	Florida
United States	Research Site	Summit	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total Tic Severity Score (Part 2 Only) Crossover Analysis Over 6 Periods	Total Tic Severity Score on the the Yale Global Tic Severity Scale - Part 2 only (lower is better), range 0 - 50	3 week period of treatment	No
Primary	Pharmacokinetics : Maximum Plasma Concentration (ng/ml) - Part 1 Only	Pharmacokinetics Part 1 only: Maximum plasma Concentration (ng/ml) Single dose Day 1 AZD5213 0.5 mg	Day 1	No
Primary	Pharmacokinetics : Time to Maximum Concentration (hr) - Part 1 Only	Pharmacokinetics Part 1 only: Time to maximum plasma concentration (hr)Single dose Day 1 AZD5213 0.5 mg	Day 1	No
Primary	Pharmacokinetics : AUC (h*ng/ ml) - Part 1 Only	Pharmacokinetics Part 1 only: Single dose Day 1 AZD5213 0.5 mg Area Under the Concentration time curve (AUC) 0 to infinity (h*ng/ml)	Day 1	No