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

NCT03661983 | Terminated Phase 4 Results DMC FDA Drug

• 2 other identifiers: 31-14-2042018-002270-48
• Study Type: interventional
• Target: 36
• Locations: 3 countries
• Sites: 42

Brief Summary

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

Conditions

Tourette's Disorder (TD)

Keywords

Aripiprazole; Tourette's Disorder; Pediatric

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Relapse During the 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.

  From Randomization up to 12 weeks in Double-blind Randomized Withdrawal Phase

Study Arms (4)

Open Label Stabilization Phase: Aripiprazole

EXPERIMENTAL

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

Double Blind Phase: Aripiprazole Full Dose

EXPERIMENTAL

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

Double Blind Phase: Aripiprazole Half Dose

EXPERIMENTAL

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

Double Blind Phase: Placebo

PLACEBO COMPARATOR

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

Interventions

Aripiprazole DRUG

Participants received aripiprazole tablets, orally as per the regimen specified in the arm description.

Also known as: OPC-14597

Double Blind Phase: Aripiprazole Full Dose; Double Blind Phase: Aripiprazole Half Dose; Open Label Stabilization Phase: Aripiprazole

Placebo DRUG

Participants received aripiprazole matching-placebo tablets, orally as per the regimen specified in the arm description.

Double Blind Phase: Placebo

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead

Study Sites (42)

Advanced Research Center

Anaheim, California, 92805, United States

Location

CT Trials - Riverside

Riverside, California, 92506, United States

Location

Syrentis Clinical Research

Santa Ana, California, 92705, United States

Location

Comprehensive Research Center

Norwich, Connecticut, 06360, United States

Location

Sarkis Clinical

Gainesville, Florida, 32607, United States

Location

Reliable Clinical Research

Hialeah, Florida, 33012, United States

Location

Eastern Research

Hialeah, Florida, 33013, United States

Location

Quest Pharmaceutical Services - Miami Research Associates

South Miami, Florida, 33143, United States

Location

Rothman Center for Pediatric Neuropsychiatry

St. Petersburg, Florida, 33701, United States

Location

Pediatric and Adolescent Neurodevelopment Associates

Atlanta, Georgia, 30328, United States

Location

Inova Clinical trials and Research Center

Fayetteville, Georgia, 30214, United States

Location

Baber Research Group

Naperville, Illinois, 60563, United States

Location

Neurobehavioral Medicine Group

Bloomfield Hills, Michigan, 48302, United States

Location

Alivation

Lincoln, Nebraska, 68526, United States

Location

The NeuroCognitive Institute

Mount Arlington, New Jersey, 07856, United States

Location

Manhattan Behavioral Medicine

New York, New York, 10036, United States

Location

Mood Disorders Consulting Medicine

New York, New York, 10036, United States

Location

Finger Lakes Clinical Research

Rochester, New York, 14618, United States

Location

New Hope Clinical Research

Charlotte, North Carolina, 28211, United States

Location

Triangle Neuropsychiatry

Durham, North Carolina, 27707, United States

Location

Quest Therapeutics of Avon Lake DBA Haidar Almhana Nieding

Avon Lake, Ohio, 44012, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

Location

Charak Center for Health and Wellness

Garfield Heights, Ohio, 44125, United States

Location

North Star Medical Research

Middleburg Heights, Ohio, 44130, United States

Location

IPS Research

Oklahoma City, Oklahoma, 73103, United States

Location

ClinMed Research Associates, Inc.

Oklahoma City, Oklahoma, 73112, United States

Location

Rivus Wellness and Research Institute

Oklahoma City, Oklahoma, 73112, United States

Location

Sooner Clinical Research

Oklahoma City, Oklahoma, 73112, United States

Location

BioBehavioral Research of Austin

Austin, Texas, 78759, United States

Location

University Hills Clinical Research

Irving, Texas, 75062, United States

Location

Psychiatric Medical Associates

Plano, Texas, 75093, United States

Location

Clinical Trials of Texas

San Antonio, Texas, 78229, United States

Location

Aspen Clinical Research - Orem

Orem, Utah, 84058, United States

Location

University of Virginia School of Medicine

Charlottesville, Virginia, 22903, United States

Location

Clinical Research Partners - Richmond

Petersburg, Virginia, 23805, United States

Location

Core Clinical Research

Everett, Washington, 98201, United States

Location

Palouse Psychiatry & Behavioral Health

Spokane, Washington, 99202, United States

Location

Kids Clinic

Ajax, Ontario, L1Z 0M1, Canada

Location

Jodha Tishon Inc.

Toronto, Ontario, M6J 3S3, Canada

Location

Vadaskert Alaptvany A Gyermekek Lelki Egeszsegeert

Budapest, 1021, Hungary

Location

Semmelweis Egyetem - I. sz. Gyermekgyógyászati Klinika

Budapest, 1083, Hungary

Location

MeSH Terms

Conditions

Tourette Syndrome

Interventions

Aripiprazole

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

This trial was terminated early due to the withdrawal of post-marketing commitment (PMC) to FDA. The planned interim analysis was not conducted either.

Results Point of Contact

• Title: Global Clinical Development
• Organization: Otsuka Pharmaceutical Development & Commercialization, Inc.

clinicaltransparency@otsuka-us.com

1-609-524-6788

Study Officials

• Eva Kohegyi, MD, MS

  Otsuka Pharmaceutical Development & Commercialization, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2018
• First Posted: September 7, 2018
• Study Start: October 13, 2018
• Primary Completion: June 30, 2020
• Study Completion: June 30, 2020
• Last Updated: March 9, 2021
• Results First Posted: January 22, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, 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

Locations

US (38); HU (2); CA (2)