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

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ClinicalTrials.gov Identifier: NCT03661983
Recruitment Status : Terminated (Lack of feasibility for completion of the trial within a reasonable time frame.)
First Posted : September 7, 2018
Results First Posted : January 22, 2021
Last Update Posted : March 9, 2021
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.

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

Condition or disease Intervention/treatment Phase
Tourette's Disorder (TD) Drug: Aripiprazole Drug: Placebo Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : October 13, 2018
Actual Primary Completion Date : June 30, 2020
Actual Study Completion Date : June 30, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Open Label Stabilization Phase: Aripiprazole
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.
Drug: Aripiprazole
Participants received aripiprazole tablets, orally as per the regimen specified in the arm description.
Other Name: OPC-14597

Experimental: Double Blind Phase: Aripiprazole Full Dose
Participants who met stabilization criteria and randomized to receive full dose of aripiprazole i.e. 5 mg or 10 mg for <50 kg participants,and 10 mg or 20 mg for >50 kg participants (2 tablets a day), based on stabilized dose in open-label stabilization phase, up to 12 weeks in Double-Blind Phase.
Drug: Aripiprazole
Participants received aripiprazole tablets, orally as per the regimen specified in the arm description.
Other Name: OPC-14597

Experimental: Double Blind Phase: Aripiprazole Half Dose
Participants who met stabilization criteria and randomized to receive half dose of aripiprazole i.e. 2 mg or 5 mg for <50 kg participants, and 5 mg or 10 mg for >50 kg participants (2 tablets a day), based on stabilized dose in open-label stabilization phase, up to 12 weeks in Double-Blind Phase.
Drug: Aripiprazole
Participants received aripiprazole tablets, orally as per the regimen specified in the arm description.
Other Name: OPC-14597

Placebo Comparator: Double Blind Phase: Placebo
Participants who met randomization criteria and randomized to receive aripiprazole matching-placebo tablets, 2 daily, orally, up to 12 weeks in Double-Blind Phase.
Drug: Placebo
Participants received aripiprazole matching-placebo tablets, orally as per the regimen specified in the arm description.




Primary Outcome Measures :
  1. Percentage of Participants With Relapse During the Double-blind Randomized Withdrawal Phase [ Time Frame: From Randomization up to 12 weeks in Double-blind Randomized Withdrawal Phase ]
    Relapse was defined as a loss of ≥ 50% of the improvement experienced during the open-label stabilization phase (i.e., improvement at the last assessment of Yale Global Tic Severity Scale (YGTSS) before randomization) on the Yale Global Tic Severity Scale Total Tic Score (YGTSS TTS). YGTSS provides an evaluation of the number, frequency, intensity, complexity, and interference of motor and phonic symptoms.



Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03661983


Locations
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Sponsors and Collaborators
Otsuka Pharmaceutical Development & Commercialization, Inc.
Investigators
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Study Director: Eva Kohegyi, MD, MS Otsuka Pharmaceutical Development & Commercialization, Inc.
  Study Documents (Full-Text)

Documents provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:
Study Protocol  [PDF] March 4, 2019
Statistical Analysis Plan  [PDF] July 6, 2020

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Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT03661983    
Other Study ID Numbers: 31-14-204
2018-002270-48 ( EudraCT Number )
First Posted: September 7, 2018    Key Record Dates
Results First Posted: January 22, 2021
Last Update Posted: March 9, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Data will be available after marketing approval in global markets, or beginning 1-3 years following article publication. There is no end date to the availability of the data.
Access Criteria: Otsuka will share data on an Otsuka-owned remotely accessible data sharing platform with Python and R analytical software. Research requests should be directed to clinicaltransparency@Otsuka-us.com
URL: http://clinical-trials.otsuka.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:
Aripiprazole
Tourette's Disorder
Pediatric
Additional relevant MeSH terms:
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Tourette Syndrome
Disease
Pathologic Processes
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tic Disorders
Movement Disorders
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Neurodevelopmental Disorders
Mental Disorders
Aripiprazole
Antidepressive Agents
Psychotropic Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Dopamine Agonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin 5-HT1 Receptor Agonists
Serotonin Receptor Agonists
Serotonin Agents
Serotonin 5-HT2 Receptor Antagonists
Serotonin Antagonists