Tourette Syndrome
Conditions
Keywords
Combined Multiple Motor and Vocal Tic Disorder; Tourette Disorder; Gilles de la Tourette Syndrome; Tourette Disease
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.
Interventions
DRUGAZD5213 and placebo
low dose AZD5213 capsules; high dose AZD5213 capsules; placebo capsules
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to 17 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Tic Severity Score (Part 2 Only) Crossover Analysis Over 6 Periods | 3 week period of treatment | Total Tic Severity Score on the the Yale Global Tic Severity Scale - Part 2 only (lower is better), range 0 - 50 |
| Pharmacokinetics : Maximum Plasma Concentration (ng/ml) - Part 1 Only | Day 1 | Pharmacokinetics Part 1 only: Maximum plasma Concentration (ng/ml) Single dose Day 1 AZD5213 0.5 mg |
| Pharmacokinetics : Time to Maximum Concentration (hr) - Part 1 Only | Day 1 | Pharmacokinetics Part 1 only: Time to maximum plasma concentration (hr)Single dose Day 1 AZD5213 0.5 mg |
| Pharmacokinetics : AUC (h*ng/ ml) - Part 1 Only | Day 1 | 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) |
Countries
United States
Participant flow
Recruitment details
Subjects between the ages of 12 and 17 with Tourette's Disorder
Pre-assignment details
There were 29 screening visits for 28 subjects, 1 subject was initially screen failed for exclusion 32 but rescreened and qualified and entered Part 1 of the study(104-4003 rescreened and qualified as 104-4004). Eligible subjects participated in Part 1 and then continued into a randomized 6 period crossover Part 2 of the study
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Part 1 & Part 2 | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Fifth Intervention | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| First Intervention | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Part 1 - Multiple Dose AZD5213 2.0 mg | Adverse Event | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Placebo Washout Fifth Intervention | Study specific withdrawal criteria | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Placebo Washout First Intervention | Condition worsened | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Screen | Screen failure | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Screen | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 14.6 years STANDARD_DEVIATION 1.76 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Nicotine use Current | 0 Participants |
| Nicotine use Never | 24 Participants |
| Nicotine use Past | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 21 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 20 Participants |
| Tourette's Disorder Duration | 75 months |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 22 / 24 | 1 / 24 | 7 / 24 | 16 / 23 | 9 / 19 | 11 / 21 | 5 / 24 |
| serious Total, serious adverse events | 2 / 24 | 0 / 24 | 1 / 24 | 0 / 23 | 0 / 19 | 1 / 21 | 0 / 24 |
Outcome results
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)
Time frame: Day 1
Population: Pharmacokinetic population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD5213 0.5 mg | Pharmacokinetics : AUC (h*ng/ ml) - Part 1 Only | 26.356 AUC (h*ng/ml) | Standard Deviation 9.155 |
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
Time frame: Day 1
Population: Pharmacokinetic population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD5213 0.5 mg | Pharmacokinetics : Maximum Plasma Concentration (ng/ml) - Part 1 Only | 3.690 Plasma concentration (ng/ml) | Standard Deviation 1.405 |
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
Time frame: Day 1
Population: Pharmacokinetic population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD5213 0.5 mg | Pharmacokinetics : Time to Maximum Concentration (hr) - Part 1 Only | 2.112 Time (hr) | Standard Deviation 1.004 |
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
Time frame: 3 week period of treatment
Population: All Part 2 participants
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD5213 0.5 mg | Total Tic Severity Score (Part 2 Only) Crossover Analysis Over 6 Periods | 24.32 Total Tic Severity Score | Standard Error 2.01 |
| AZD5213 2.0 mg | Total Tic Severity Score (Part 2 Only) Crossover Analysis Over 6 Periods | 25.41 Total Tic Severity Score | Standard Error 2.05 |
| Placebo | Total Tic Severity Score (Part 2 Only) Crossover Analysis Over 6 Periods | 22.99 Total Tic Severity Score | Standard Error 2.03 |
Comparison: Comparison with placebop-value: 0.0087ANCOVA
p-value: 0.1198ANCOVA