Tourette's Disorder (TD)Phase 4NCT03661983
Trial to Evaluate the Long-term Efficacy of Oral Aripiprazole in the Treatment of Pediatric Participants With Tourette's Disorder
A Phase 4 study testing Aripiprazole in people with Tourette's Disorder (TD), run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 42 sites in 3 countries.
Trial summary
To evaluate the long-term efficacy of oral aripiprazole in pediatric participants for the treatment of Tourette's Disorder (TD). Read more about this study
- Who is it for?
- Ages 6 to 17 years
- Conditions the study is for
- Tourette's Disorder (TD)
- What is being tested?
- Aripiprazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 42 sitesin 3 countries
- Study dates
- 13 Oct 2018to 30 Jun 2020
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 20Show fewer
- 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
Trial locations and contacts
42 sites in 3 countries.
42 sites in 3 countries
United States38 sites
Advanced Research Center
Anaheim, California, 92805
Pediatric and Adolescent Neurodevelopment Associates
Atlanta, Georgia, 30328
BioBehavioral Research of Austin
Austin, Texas, 78759
Quest Therapeutics of Avon Lake DBA Haidar Almhana Nieding
Avon Lake, Ohio, 44012
Neurobehavioral Medicine Group
Bloomfield Hills, Michigan, 48302
New Hope Clinical Research
Charlotte, North Carolina, 28211
University of Virginia School of Medicine
Charlottesville, Virginia, 22903
University of Cincinnati
Cincinnati, Ohio, 45219
University Hospitals Case Medical Center
Cleveland, Ohio, 44106
Triangle Neuropsychiatry
Durham, North Carolina, 27707
Core Clinical Research
Everett, Washington, 98201
Inova Clinical trials and Research Center
Fayetteville, Georgia, 30214
Sarkis Clinical
Gainesville, Florida, 32607
Charak Center for Health and Wellness
Garfield Heights, Ohio, 44125
Reliable Clinical Research
Hialeah, Florida, 33012
Eastern Research
Hialeah, Florida, 33013
University Hills Clinical Research
Irving, Texas, 75062
Alivation
Lincoln, Nebraska, 68526
North Star Medical Research
Middleburg Heights, Ohio, 44130
The NeuroCognitive Institute
Mount Arlington, New Jersey, 07856
Baber Research Group
Naperville, Illinois, 60563
Manhattan Behavioral Medicine
New York, New York, 10036
Mood Disorders Consulting Medicine
New York, New York, 10036
Comprehensive Research Center
Norwich, Connecticut, 06360
IPS Research
Oklahoma City, Oklahoma, 73103
ClinMed Research Associates, Inc.
Oklahoma City, Oklahoma, 73112
Rivus Wellness and Research Institute
Oklahoma City, Oklahoma, 73112
Sooner Clinical Research
Oklahoma City, Oklahoma, 73112
Aspen Clinical Research - Orem
Orem, Utah, 84058
Clinical Research Partners - Richmond
Petersburg, Virginia, 23805
Psychiatric Medical Associates
Plano, Texas, 75093
CT Trials - Riverside
Riverside, California, 92506
Finger Lakes Clinical Research
Rochester, New York, 14618
Clinical Trials of Texas
San Antonio, Texas, 78229
Syrentis Clinical Research
Santa Ana, California, 92705
Quest Pharmaceutical Services - Miami Research Associates
South Miami, Florida, 33143
Palouse Psychiatry & Behavioral Health
Spokane, Washington, 99202
Rothman Center for Pediatric Neuropsychiatry
St. Petersburg, Florida, 33701
Canada2 sites
Kids Clinic
Ajax, Ontario, L1Z 0M1
Jodha Tishon Inc.
Toronto, Ontario, M6J 3S3
Hungary2 sites
Vadaskert Alaptvany A Gyermekek Lelki Egeszsegeert
Budapest, 1021
Semmelweis Egyetem - I. sz. Gyermekgyógyászati Klinika
Budapest, 1083
About this study
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
To evaluate the long-term efficacy of oral aripiprazole in pediatric participants for the treatment of Tourette's Disorder (TD).
Read the 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.
- Conditions
- Tourette's Disorder (TD)
- Being tested
- Aripiprazole, Placebo
- Keywords
- Aripiprazole, Tourette's Disorder, Pediatric
- Medical subject headings
- Tourette Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AripiprazoleDrug
Also called OPC-14597
Participants received aripiprazole tablets, orally as per the regimen specified in the arm description.
PlaceboDrug
Participants received aripiprazole matching-placebo tablets, orally as per the regimen specified in the arm description.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From Randomization up to 12 weeks in Double-blind Randomized Withdrawal Phase
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2018
- Study start13 Oct 2018
- Primary completion30 Jun 2020
- Study completion30 Jun 2020
Why it stopped: Lack of feasibility for completion of the trial within a reasonable time frame.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Tourette's Disorder (TD)Studies of the same condition, open and under way.
- More trials run by Otsuka Pharmaceutical Development & Commercialization, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Eva Kohegyi, MD, MS, Study director, Otsuka Pharmaceutical Development & Commercialization, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03661983
- Sponsor's protocol ID
- 31-14-204
- Other IDs
- 2018-002270-48, 2018
- Status last verified
- Feb 2021
- First submitted
- 5 Sep 2018
- Last updated
- 9 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03661983
- Acronym / sponsor ID
- 31-14-204
- Conditions
- Tourette's Disorder (TD)
- Keywords
- Aripiprazole, Tourette's Disorder, Pediatric
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of feasibility for completion of the trial within a reasonable time frame.
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Otsuka Pharmaceutical Development & Commercialization, Inc.Industry (pharma, biotech, devices)
- Study start
- 13 Oct 2018 (actual)
- Primary completion
- 30 Jun 2020 (actual)
- Study completion
- 30 Jun 2020 (actual)
- First posted
- 7 Sep 2018 (actual)
- Results
- Posted 22 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Open Label Stabilization Phase: Aripiprazole | Experimental | Drug: AripiprazoleParticipants 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. |
| Double Blind Phase: Aripiprazole Full Dose | Experimental | Drug: AripiprazoleParticipants 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. |
| Double Blind Phase: Aripiprazole Half Dose | Experimental | Drug: AripiprazoleParticipants 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. |
| Double Blind Phase: Placebo | Placebo comparator | Drug: PlaceboParticipants who met randomization criteria and randomized to receive aripiprazole matching-placebo tablets, 2 daily, orally, up to 12 weeks in Double-Blind Phase. |
Who may qualify
- Ages
- 6 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AripiprazoleAlso: OPC-14597Participants received aripiprazole tablets, orally as per the regimen specified in the arm description. | Drug | Double Blind Phase: Aripiprazole Full Dose, Double Blind Phase: Aripiprazole Half Dose, Open Label Stabilization Phase: Aripiprazole |
| PlaceboParticipants received aripiprazole matching-placebo tablets, orally as per the regimen specified in the arm description. | Drug | Double Blind Phase: Placebo |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eva Kohegyi, MD, MS study director
Otsuka Pharmaceutical Development & Commercialization, Inc.
42 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Aripiprazole in people with Tourette's Disorder (TD), run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 42 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 42 sites in United States, Canada, Hungary. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2021.