Clinical trial NCT03661983: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Tourette's Disorder (TD)
Keywords: Aripiprazole
Tourette's Disorder
Pediatric
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor class: INDUSTRY
First posted: 2018-09-07
Enrollment: 36
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Percentage of Participants With Relapse During the Double-blind Randomized Withdrawal Phase
timeFrame: From Randomization up to 12 weeks in Double-blind Randomized Withdrawal Phase
Secondary outcomes:
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Advanced Research Center
state: California
city: Riverside
country: United States
facility: CT Trials - Riverside
state: California
city: Santa Ana
country: United States
facility: Syrentis Clinical Research
state: California
city: Norwich
country: United States
facility: Comprehensive Research Center
state: Connecticut
city: Gainesville
country: United States
facility: Sarkis Clinical
state: Florida
city: Hialeah
country: United States
facility: Reliable Clinical Research
state: Florida
city: Hialeah
country: United States
facility: Eastern Research
state: Florida
city: Saint Petersburg
country: United States
facility: Rothman Center for Pediatric Neuropsychiatry
state: Florida
city: South Miami
country: United States
facility: Quest Pharmaceutical Services - Miami Research Associates
state: Florida
city: Atlanta
country: United States
facility: Pediatric and Adolescent Neurodevelopment Associates
state: Georgia
city: Fayetteville
country: United States
facility: Inova Clinical trials and Research Center
state: Georgia
city: Naperville
country: United States
facility: Baber Research Group
state: Illinois
city: Bloomfield Hills
country: United States
facility: Neurobehavioral Medicine Group
state: Michigan
city: Lincoln
country: United States
facility: Alivation
state: Nebraska
city: Mount Arlington
country: United States
facility: The NeuroCognitive Institute
state: New Jersey
city: New York
country: United States
facility: Manhattan Behavioral Medicine
state: New York
city: New York
country: United States
facility: Mood Disorders Consulting Medicine
state: New York
city: Rochester
country: United States
facility: Finger Lakes Clinical Research
state: New York
city: Charlotte
country: United States
facility: New Hope Clinical Research
state: North Carolina
city: Durham
country: United States
facility: Triangle Neuropsychiatry
state: North Carolina
city: Avon Lake
country: United States
facility: Quest Therapeutics of Avon Lake DBA Haidar Almhana Nieding
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Garfield Heights
country: United States
facility: Charak Center for Health and Wellness
state: Ohio
city: Middleburg Heights
country: United States
facility: North Star Medical Research
state: Ohio
city: Oklahoma City
country: United States
facility: IPS Research
state: Oklahoma
city: Oklahoma City
country: United States
facility: ClinMed Research Associates, Inc.
state: Oklahoma
city: Oklahoma City
country: United States
facility: Rivus Wellness and Research Institute
state: Oklahoma
city: Oklahoma City
country: United States
facility: Sooner Clinical Research
state: Oklahoma
city: Austin
country: United States
facility: BioBehavioral Research of Austin
state: Texas
city: Irving
country: United States
facility: University Hills Clinical Research
state: Texas
city: Plano
country: United States
facility: Psychiatric Medical Associates
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas
state: Texas
city: Orem
country: United States
facility: Aspen Clinical Research - Orem
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia School of Medicine
state: Virginia
city: Petersburg
country: United States
facility: Clinical Research Partners - Richmond
state: Virginia
city: Everett
country: United States
facility: Core Clinical Research
state: Washington
city: Spokane
country: United States
facility: Palouse Psychiatry & Behavioral Health
state: Washington
city: Ajax
country: Canada
facility: Kids Clinic
state: Ontario
city: Toronto
country: Canada
facility: Jodha Tishon Inc.
state: Ontario
city: Budapest
country: Hungary
facility: Vadaskert Alaptvany A Gyermekek Lelki Egeszsegeert
city: Budapest
country: Hungary
facility: Semmelweis Egyetem - I. sz. Gyermekgyógyászati Klinika
Study officials:
affiliation: Otsuka Pharmaceutical Development & Commercialization, Inc.
name: Eva Kohegyi, MD, MS
role: STUDY_DIRECTOR
References: