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

Study Overview
=================
Brief 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.

Detailed 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.

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

Conditions
-----------------
Tourette Syndrome

Intervention / Treatment
-----------------
* Drug: AZD5213 and placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female, between the ages of ≥ 12 and < 18 years at baseline (Day 1). 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. Yale Global Tic Severity Scale (YGTSS) Total Tic Severity Score (TTS) ≥ 20 at Screen and baseline (Day 1). Symptoms of Tourette's Disorder must impair school, occupational, and/or social function. 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: Prior participation in any AZD5213 study. 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). Pregnant or breast-feeding females. History of seizure disorder other than a single childhood febrile seizure. 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.

Ages Eligible for Study
-----------------
Minimum Age: 12 Years
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: AZD5213 and placebo<br>* low dose AZD5213 capsules; high dose AZD5213 capsules; placebo capsules<br>|
| Experimental: low dose AZD5213<br> | Drug: AZD5213 and placebo<br>* low dose AZD5213 capsules; high dose AZD5213 capsules; placebo capsules<br>|
| Experimental: high dose AZD5213<br> | Drug: AZD5213 and placebo<br>* low dose AZD5213 capsules; high dose AZD5213 capsules; placebo capsules<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Combined Multiple Motor and Vocal Tic Disorder; Tourette Disorder; Gilles de la Tourette Syndrome; Tourette Disease