Trial to Evaluate the Long-term Efficacy of Oral Aripiprazole in the Treatment of Pediatric Subjects With Tourette’s Disorder

Brief Title

Trial to Evaluate the Long-term Efficacy of Oral Aripiprazole in the Treatment of Pediatric Participants With Tourette's Disorder

Official Title

A Randomized, Placebo-controlled Trial to Evaluate the Long-term (ie, Maintenance) Efficacy of Oral Aripiprazole in the Treatment of Pediatric Subjects With Tourette's Disorder

Brief Summary

      To evaluate the long-term efficacy of oral aripiprazole in pediatric participants for the
      treatment of Tourette's Disorder (TD).
    

Detailed Description

      This study will evaluate the long-term efficacy of oral aripiprazole in the treatment of
      pediatric participants with Tourette's Disorder (TD). The trial consists of 3 distinct
      phases: a pretreatment phase, open-label stabilization phase, and a double-blind randomized
      withdrawal phase.
    

Study Phase

Phase 4

Study Type

Interventional

Primary Outcome

Percentage of Participants With Relapse During the Double-blind Randomized Withdrawal Phase

Condition

Tourette's Disorder (TD)

Intervention

Aripiprazole

Study Arms / Comparison Groups

 Open Label Stabilization Phase: Aripiprazole

Description:  Participants began treatment with aripiprazole at a 2.0 mg/day dose, with the dose titrated to 5.0 mg/day after 2 days. Subsequent dose adjustments were based on the participant's weight to achieve optimum control of tics up to the maximum recommended doses based on the United States Labeling, up to Week 8 and then continued on the most stabilized dose up to minimum Week 14 or maximum Week 20. Participants who met stabilization criteria were randomized to Double-blind Randomization Phase.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

36

Start Date

October 13, 2018

Completion Date

June 30, 2020

Primary Completion Date

June 30, 2020

Eligibility Criteria

        Inclusion Criteria:

          -  The participant is a male or female child or adolescent, 6 to 17 years of age
             (inclusive) at the time of signing the informed consent/assent.

          -  The participant meets current Diagnostic and Statistical Manual of Mental Disorders
             5th Edition (DSM-5) diagnostic criteria for TD, documented at screening and made by an
             adequately trained clinician, as confirmed by the Kiddie Schedule for Affective
             Disorders and Schizophrenia - Present and Lifetime Version.

          -  The participant has a Total Tic Score (TTS) ≥ 20 on the Yale Global Tic Severity Scale
             (YGTSS) at screening and baseline (Day 1).

          -  The participant, a caregiver, and the investigator must all agree that the presenting
             tic symptoms cause impairment in the participant's normal routines, which include
             academic achievement, occupational functioning, social activities, and/or
             relationships.

          -  Females of childbearing potential (all female participants ≥ 12 years of age and all
             female participants < 12 years of age if menstruation has started) must have a
             negative pregnancy test and must not be pregnant or lactating.

          -  Written informed consent must be obtained from the participant or a legally acceptable
             representative (eg, guardian or caregiver), in accordance with requirements of the
             trial site's institutional review board (IRB)/independent ethics committee (IEC) and
             local regulatory requirements, prior to the initiation of any protocol-required
             procedures. In addition, the participant, as required by the trial center's IRB/IEC,
             must provide informed assent at screening and as such must be able to understand that
             he or she can withdraw from the trial at any time.

          -  Ability, in the opinion of the principal investigator, of the participant and the
             participant's legally acceptable representative (e.g., guardian) or caregiver(s) to
             understand the nature of the trial and follow protocol requirements, including the
             prescribed dosage regimens, tablet ingestion, and discontinuation of prohibited
             concomitant medications, to read and understand the written word in order to complete
             participant-reported outcomes measures, and to be reliably rated on assessment scales.

        Exclusion Criteria:

          -  The participant presents with a clinical presentation and/or history that is
             consistent with another neurologic condition that may have accompanying abnormal
             movements. These include, but are not limited to, the following: Transient tic
             disorder; Huntington's disease; Parkinson's disease; Sydenham's chorea; Wilson's
             disease; Mental retardation; Pervasive developmental disorder; Tardive dyskinesia;
             Traumatic brain injury; Stroke; Restless legs syndrome.

          -  The participant has a history of schizophrenia, bipolar disorder, or other psychotic
             disorder.

          -  Participants who receive psychostimulants for the treatment of attention-deficit
             hyperactivity disorder (ADHD) and who have developed and/or had exacerbations of the
             tic disorder after the initiation of stimulant treatment. (Note that participants with
             ADHD who are treated with psychostimulants and have not developed new tics or a
             worsening of their current tics can be included if all other enrollment obligations
             are met).

          -  The participant currently has a primary diagnosis that meets DSM-5 criteria for mood
             disorder.

          -  The participant has severe obsessive-compulsive disease, as evidenced by a Children's
             Yale-Brown Obsessive Compulsive Scale (CY-BOCS) score > 16.

          -  The participant has taken aripiprazole within 1 month (30 days) of the screening
             visit.

          -  The participant has a history of neuroleptic malignant syndrome.

          -  Participant is a sexually active male or female of childbearing potential (FOCBP) (all
             female participants ≥ 12 years of age and all female participants < 12 years of age if
             menstruation has started) who will not agree to practice 2 acceptable methods of birth
             control or who will not remain abstinent during the trial and for 30 or 90 days
             following the last dose of Investigational medicinal product (IMP) for females and
             males, respectively. Abstinence will be permitted if it is confirmed and documented at
             every trial visit.

          -  The participant represents a significant risk of committing suicide based on history
             (suicide attempt in past 1 year).

          -  The participant has a body weight < 16 kg.

          -  Participants who have taken neuroleptic or antiparkinson drugs within 14 days prior to
             baseline.

          -  Participants requiring cognitive-behavioral therapy (CBT) for TD during the trial
             period. CBT for other nonexclusionary disorder must remain consistent through the
             trial.

          -  The participant has met DSM-5 criteria for any significant psychoactive substance use
             disorder within the past 3 months.

          -  A positive drug screen for cocaine, alcohol, or other drugs of abuse (excluding
             caffeine, nicotine, or prescribed psychostimulants for ADHD). Investigators can choose
             to repeat a positive drug screen one time during screening period after concurrence
             from the medical monitor. A second positive test for any drug of abuse would be
             exclusionary.

          -  Participant requiring medication not allowed per protocol.

          -  Use of any cytochrome P450 (CYP)2D6 and CYP3A4 inhibitors or CYP3A4 inducers within 14
             days prior to baseline and for the duration of the trial.

          -  Other nutritional or dietary supplements and nonprescription herbal preparations for
             TD (eg, cannabinoids, N-acetylcysteine, omega-3 fatty acids, kava extracts, GABA
             supplements) within 7 days prior to baseline and for the duration of the trial, unless
             approved in advance by the medical monitor.

          -  The inability to swallow tablets or tolerate oral medication.

          -  Participant has participated in a clinical trial involving either study medication or
             interventional (non-medication) treatment for TD within the last 60 days.

          -  The following laboratory test results, vital signs and electrocardiogram (ECG) results
             are exclusionary: Platelets ≤ 75,000/mm^3; Hemoglobin ≤ 9 g/dL; Neutrophils, absolute
             ≤ 1000/mm^3; Aspartate aminotransferase > 3 × upper limit of normal (ULN) as defined
             by the central laboratory; Alanine aminotransferase > 3 × ULN as defined by the
             central laboratory; Creatinine ≥ 2 mg/dL; Diastolic blood pressure > 105 mmHg;
             Corrected QT interval ≥ 450 msec (males) or ≥ 470 msec (females) using the corrected
             QT interval for heart rate using Fridericia's formula
      

Gender

All

Ages

6 Years - 17 Years

Accepts Healthy Volunteers

No

Contacts

Eva Kohegyi, MD, MS, , 

Location Countries

Canada

Location Countries

Canada

NCT ID

NCT03661983

Organization ID

31-14-204

Secondary IDs

2018-002270-48

Responsible Party

Sponsor

Study Sponsor

Otsuka Pharmaceutical Development & Commercialization, Inc.

Study Sponsor

Eva Kohegyi, MD, MS, Study Director, Otsuka Pharmaceutical Development & Commercialization, Inc.

Verification Date

February 2021