Aripiprazole Oral Solution in the Treatment of Children and Adolescents With Tourette's Syndrome

A Multicenter, Randomized, Double-Blind, Flexible-Dosed, Placebo-Controlled, Parallel-Group Clinical Trial Evaluating the Efficacy and Safety of Aripiprazole Oral Solution in Children and Adolescents With Tourette's Syndrome

This study is a multicenter, randomized, double-blind, placebo-controlled trial designed to assess the safety, efficacy, tolerability and steady-state plasma trough concentration of flexible-dosed aripiprazole once-daily administration in children and adolescents with Tourette's syndrome. A total of around 120 subjects will be randomized to aripiprazole (2~20 mg) or placebo in a 1:1 ratio (approximately 60 subjects in each group), for treatment of 8 weeks.

Screening phase: It can last up to 42 days, including the screening visit (V1), a washout period when applicable, additional screening visit (V1a) and baseline visit (V2). The screening phase will serve the following purposes: 1) To allow for appropriate washout of prohibited medications; 2) To review the screening data; 3) To establish a pretreatment baseline of critical outcome measures.

Treatment phase: It lasts 8 weeks; the purpose of the treatment phase is to assess the efficacy, safety, tolerability and steady-state plasma trough concentration of aripiprazole in the treatment of children and adolescents with Tourette's syndrome.

Safety follow-up phase: All subjects will be followed up for safety (adverse events) at Day 16 after the final medication via telephone

Inclusion Criteria:

1. Written informed consent form must be obtained from a legal guardian (and the subject)
2. The subject and the designated guardian(s) or caregiver(s) are able to comprehend and satisfactorily comply with the protocol requirements, as evaluated by the investigator.
3. The subject is a male or female child or adolescent, 6-18 years of age (6≤ Age <18) at the time of Baseline Visit (V2);
4. The subject meets the current DSM-IV-TR diagnostic criteria for Tourette's syndrome and requires drug therapy;
5. The subject has a TTS ≥ 22 on the YGTSS at Baseline Visit (V2);

Exclusion Criteria:

1. Women of childbearing potential (WOCBP) who will not commit to utilizing the approved birth control methods or who will not remain abstinent during the trial and for 8 weeks following the final dose of study drug; Note: WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal [defined as amenorrhea 12 consecutive months; or women on hormone replacement therapy with documented serum follicle stimulating hormone level ≥ 35 mIU/mL].

2. Females who have a positive pregnancy test result or who are pregnant or breast-feeding;

3. Subjects who have secondary tic symptoms accompanied by late-onset tics, Huntington's chorea, neuroacanthocytosis, mental retardation, or autism;

4. Subjects who have comorbidities requiring drug therapy, such as attention deficit / attention-deficit hyperactivity, obsessive-compulsive disorder, or oppositional defiant disorder (if a case is judged by the investigator that drug therapy is not required for any of the above diseases during this study, then the patient is eligible to participate in this trial);

5. Subjects who have lower intelligence;

6. Subjects who have a current diagnosis of bipolar disorder, mental disorder, schizophrenia, or depressive disorder;

7. Subjects who have records of neuroleptic malignant syndrome;

8. Subjects who have experienced episodes of epileptic seizure in the past year;

9. Subjects who have a history of severe traumatic brain injury or stroke;

10. Subjects who have any unstable medical conditions or are currently ill (e.g., congenital heart disease, arrhythmia or cancer), which, in the investigator's judgment, will put them at a risk of major adverse event during this trial, or will interfere with safety and efficacy assessments

11. Subjects who require both drug therapy and cognitive-behavioral therapy (CBT, including habitual inversion therapy, cognitive therapy, relaxation training, etc.) during the trial period;

12. Patients with the following laboratory test results, vital signs, measurements, and electrocardiogram (ECG) results will be excluded:

    • QTc > 450 msec (male), QTc > 470 msec (female)
    • Platelets (< lower limit)
    • Hemoglobin (< lower limit)
    • Neutrophils (< lower limit)
    • AST (SGOT) or ALT (SGPT) (> upper limit)
    • Creatinine (> upper limit) Subjects should be excluded if they have any other abnormal laboratory tests, vital sign results, or ECG findings which in the investigator's judgment is medically significant and will impact the safety of the subject or the interpretation of the trial results;

13. Subjects who have a body weight of lower than 15 kg;

14. Subjects who have been known to be with allergy or hypersensitivity to aripiprazole or other dihydroquinolones (e.g., carteolol, vesnarinone and cilostazol);

15. Subjects who have participated in any clinical trial of any drugs within the past one month;

16. Subjects who may require concomitant treatments prohibited as per the protocol during the trial period (referring to Section 7 Prohibited and Restricted Therapies);

17. Subjects who were previously enrolled in clinical trials of aripiprazole (excluding investigator-sponsored trials);

18. Subjects who are considered to have developed resistance to antipsychotic drugs by the investigator due to lack of efficacy after receiving 2 different antipsychotic drugs at reasonable doses and at least 3 weeks of treatment with each respectively;

19. Subjects who are considered to have developed resistance to aripiprazole by the investigator due to lack of efficacy after an adequate time of treatment with adequate dose;