Safety and Tolerability Study of Once-weekly Oral Aripiprazole in Children and Adolescents With Tourette's Disorder

Study at a glance

From the registry record, last updated by the sponsor on 7 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title

An Open-Label, Multicenter Study Evaluating the Safety and Tolerability of Once-weekly Oral Aripiprazole in Children and Adolescents With Tourette's Disorder

ClinicalTrials.gov ID

NCT01416441

Acronym / sponsor ID

31-10-274

Conditions

Tourette's Disorder

Keywords

Tourette's Disorder, Tic Disorders

Phase

Phase 3

Study type

Interventional

Recruitment status

Completed

Enrolment

170 participants (actual)

Lead sponsor

Otsuka Pharmaceutical Development & Commercialization, Inc.Industry (pharma, biotech, devices)

Study start

19 Oct 2011 (actual)

Primary completion

13 Mar 2014 (actual)

Study completion

13 Mar 2014 (actual)

First posted

15 Aug 2011 (estimated)

Results

Posted 7 Oct 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose

Treatment

Allocation

Not applicable

Intervention model

Single group

Masking

None (open label)

Number of arms

1

Who may qualify

Ages

7 to 18 years

Sex

All

Healthy volunteers

Not accepted

Age groups

Child, Adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

1. Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Severe TEAEs and TEAEs Leading Treatment Discontinuation

   Time frame: From signing of the informed consent up to 30 days after the last dose (Up to Week 52)

   An Adverse Event (AE) is defined as any untoward medical occurrence in a participant enrolled in a clinical trial and which did not necessarily have a causal relationship with the study medication. Treatment emergent adverse events (TEAE) are adverse events occurring after the onset of study drug administration.

2. Number of Participants With Clinically Significant Changes in Laboratory Parameter Values

   Time frame: Baseline to Week 52

   The laboratory values were one of the parameters to measure the safety and tolerability of individual participants. Participants with potentially clinically significant lab values in serum chemistry, hematology, urinalyses and prolactin tests that were identified based on pre-defined criteria were reported. Any value outside the normal range was flagged for the attention of the investigator who assessed whether or not a flagged value is of clinical significance.

3. Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values

   Time frame: Baseline to Week 52

   Incidence of clinically relevant abnormal ECG values were reported as change from Baseline in heart rate (Tachycardia - ≥15 beats per minute (bpm), Bradycardia ≤15 bpm; Rhythm (Sinus tachycardia ≥15 bpm increase, Sinus bradycardia decrease of ≥15 bpm from Baseline); Presence of - supraventricular premature beat; ventricular premature beat; supraventricular tachycardia; ventricular tachycardia; atrial fibrillation and flutter. Conduction - Presence of primary, secondary or tertiary atrioventricular block, left bundle-branch block, right bundle-branch block, pre-excitation syndrome, other intraventricular conduction blocked QRS ≥0.12 second increase of ≥0.02 second. Acute, subacute or old Infarction, Presence of myocardial ischemia, symmetrical T-wave inversion. Increase in QTc - QTc ≥450 msec ≥10% increase. Any clinically significant change from Baseline assessed by the Investigator are reported.

4. Number of Participants With Emergence of Suicidal Ideation, TEAEs Related to Suicide and Suicidality and Suicide Ideation From the Potential Suicide Events Recorded on the Columbia-Suicide Severity Rating Scale (C-SSRS)

   Time frame: Baseline to Week 52

   Suicidality was defined as reporting at least one occurrence of any suicidal behavior or suicidal ideation. Suicidal behavior was defined as reporting any type of suicidal behaviors (actual attempt, interrupted attempt, aborted attempt, and preparatory acts or behavior). Suicidal ideation was defined as reporting any type of suicidal ideation. The suicidal ideation intensity total score is the sum of intensity scores of 5 items (frequency, duration, controllability, deterrents, and reasons for ideation). The score of each intensity item ranges from 0 (none) to 5 (worst) which leads to the range of the total score from 0 to 25. A missing score of any item resulted in a missing total score. If no suicidal ideation was reported, a score of 0 was given to the intensity scale.

5. Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Score

   Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 32, 40, 52; Last Visit (Week 52 or early termination Visit before Week 52)

   The AIMS Scale is an extrapyramidal symptoms (EPS) rating scale. The AIMS is a 12 item scale. The first 10 items e.g. facial and oral movements (items 1-4), extremity movements (items 5 and 6), trunk movements (item 7), investigators global assessment of dyskinesia (items 8 to 10) are rated from 0 to 4 (0=best, 4=worst). Items 11 and 12, related to dental status, have dichotomous responses, 0=no and 1=yes. The AIMS Total Score is the sum of the ratings for the first seven items. The possible total scores are from 0 to 28. A negative change from Baseline indicates improvement.

6. Mean Change From Baseline in Body Mass Index (BMI)

   Time frame: Baseline and Weeks 12, 24, 52 and Last Visit (Week 52 or early termination Visit before Week 52)

   The BMI kilogram/meter square (i.e. kg/m^2) was calculated from the Baseline height and the weight at the current visit using one of the following formulae, as appropriate: Weight (kg) divided by [Height (meters)]^2.

7. Number of Participants With Clinically Significant Changes in Vital Signs

   Time frame: Baseline to Week 52

   Vital signs assessments included orthostatic (supine and standing) blood pressure (BP) measured as millimeter of mercury [mmHg]), heart rate, (measured in beats per minute [bpm]), body weight (measured in kilograms [kg]) and body temperature. Incidence of clinically relevant abnormal values in heart rate, systolic and diastolic blood pressure and weight were identified based on pre-defined criteria. Orthostatic assessments of blood pressure and heart rate were made after the participant has been supine for at least 5 minutes and again after the participant has been standing for approximately 2 minutes, but not more than 3 minutes.

8. Mean Change From Baseline in Simpson Angus Scale (SAS) Score

   Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 32, 40, 52; Last Visit (Week 52 or early termination Visit before Week 52)

   The SAS is a rating scale used to measure Extrapyramidal symptoms (EPS). The SAS scale consists of a list of 10 symptoms of parkinsonism (gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, head rotation, glabella tap, tremor, salivation, and akathisia), with each item rated from 0 to 4, with 0 being normal and 4 being the worst. The SAS Total score is sum of ratings for all 10 items, with possible Total scores from 0 to 40. A negative change from Baseline indicates improvement.

9. Mean Change From Baseline in Barnes Akathisia Rating Scale (BARS) Score

   Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 32,40, 52; Last Visit (Week 52 or early termination Visit before Week 52)

   The BARS was an EPS rating scale. The BARS was used to assess the presence and severity of akathisia. This scale consists of 4 items. Only the 4th item, the Global Clinical Assessment of Akathisia, was evaluated in this trial. This item is rated on a 6 point scale, with 0 being best (absent) and 5 being worst (severe akathisia). A negative change from Baseline indicates improvement.

10. Mean Change From Baseline in Average Score of Attention-Deficit Disorder/Attention-Deficit Hyperactivity Disorder (ADD/ADHD) Sub-scale of the Swanson, Nolan and Pelham-IV (SNAP-IV)

    Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 32,40, 52; Last Visit (Week 52 or early termination Visit before Week 52)

    The SNAP-IV, ADHD Inattention subscale contains 19 items, items 1 to 9 measure inattention, items 11 to 19 measure hyperactivity/impulsivity, and item 10 for inattention domain that scores the intensity of each item during the last seven days on a 0 to 3 scale (0=not at all, 1=just a little, 2=pretty much, 3=very much). The lowest possible score is 0; highest is 57. The negative change from Baseline indicates improvement.

11. Mean Change From Baseline in Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) Total Score

    Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 32,40, 52; Last Visit (Week 52 or early termination Visit before Week 52)

    The CY-BOCS is used to assess characteristics of obsession and compulsion for the week prior to the interview. Nineteen items are rated in the CY-BOCS, but the total score is the sum of only items 1 to 10 (excluding items 1b and 6b). The obsession and compulsion subtotals are the sums of items 1 to 5 (excluding 1b) and 6 to 10 (excluding 6b), respectively. A missing value for any CY-BOCS item scale could result in a missing total score or obsession and compulsion subtotals of which the item scale is a component. At baseline, the full CY-BOCS interview is conducted. At all post-baseline time points, the "Questions on Obsessions" (items 1 to 5) and "Questions on Compulsions" (items 6 to 10) are reviewed and the target symptoms identified at baseline are the primary focus for rating severity. CY-BOCS total score could range from 0 to 40. Higher scores indicate worse outcome. A negative change from Baseline indicates improvement.

12. Mean Change From Baseline in Children's Depression Rating Scale Revised (CDRS-R) Total Score

    Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 32,40, 52; Last Visit (Week 52 or early termination Visit before Week 52)

    The CDRS-R is composed of 17 interviewer-rated symptom areas: impaired schoolwork, difficulty having fun, social withdrawal, appetite disturbance, sleep disturbance, excessive fatigue, physical complaints, irritability, excessive guilt, low self-esteem, depressed feelings, morbid ideas, suicidal ideas, excessive weeping, depressed facial affect, listless speech, and hypoactivity. The CDRS-R total score is the sum of scores for the 17 symptom areas. A missing value for any CDRS-R item scale or a not rated item scale (indicated by the value of 0) could result in a missing total score. The CDRS-R total score is the sum of scores for the 17 symptom areas and could range from 17 to 113 with higher values indicating worse outcome. A negative change from Baseline indicates improvement.

13. Mean Change From Baseline in Pediatric Anxiety Rating Scale (PARS) Total Severity Score

    Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 32,40, 52; Last Visit (Week 52 or early termination Visit before Week 52)

    The PARS has 2 sections: the symptom checklist and the severity items. The symptom checklist is used to determine the child's repertoire of symptoms during the past week. Information is elicited from the child and parent(s) and the rater then combines information from all informants using his/her best judgment. The 7-item severity list is used to determine severity of symptoms and the PARS total score. The time frame for the PARS rating is the past week. Only those symptoms endorsed for the past week are included in the symptom checklist and rated on the severity items. The PARS total severity score is the sum of items 2, 3, 5, 6, and 7. The total severity score ranges from 0 to 25, with 25 being the worst. Codes "8" (Not applicable) and "9" (Does not know) are not included in the summation (ie, equivalent to a score of 0 in the summation). A negative change from Baseline indicates improvement.

14. Mean Change From Baseline in Body Weight

    Time frame: Baseline to Weeks 12, 24, 52 and Last Visit (Week 52 or early termination Visit before Week 52)

15. Mean Change From Baseline in Waist Circumference

    Time frame: Baseline to Weeks 12, 24, 52 and Last Visit (Week 52 or early termination Visit before Week 52)

    Waist circumference was recorded before a participant's meal and at approximately the same time at each visit. Measurement was accomplished by locating the upper hip bone and the top of the right iliac crest and placing the measuring tape in a horizontal plane around the abdomen at the level of the crest. Before reading the tape measure, the assessor assured that the tape was snug, but did not compress the skin, and is parallel to the floor. The measurement was made at the end of a normal exhalation.

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 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.

Related trials for Tourette's Disorder

• Not yet recruiting

  Evaluating and Promoting Resilience in Adolescents With Tourette Syndrome

  Tourette Syndrome, Tic Disorders

• Not yet recruiting

  Transcutaneous Auricular Vagus Nerve Stimulation for Chronic Tic Disorders/Tourette's Syndrome in Children and Adolescents

  Tourette Syndrome, Chronic Tic Disorder

• Recruiting

  Deep Brain Stimulation Therapy in Movement Disorders

  Parkinson's Disease

• Recruiting

  Exploring the Role of Neuroactive Steroids in Tourette Syndrome

  Tourette Syndrome in Children

• Active, not recruiting

  Tourette Deep Brain Stimulation (DBS) Target Detection & Suppression

  Tourette Syndrome

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.

80 sites in 10 countries: see every site and its status.