Tideglusib vs. Placebo in the Treatment of Adolescents With Autism Spectrum Disorders (TIDE)

A Randomized Placebo-controlled Trial of Tideglusib vs. Placebo in the Treatment of Adolescents With Autism Spectrum Disorders (ASD)

This study will examine the safety and efficacy of tideglusib vs. placebo for the treatment of core symptom domains in adolescents with Autism Spectrum Disorders

Study Overview

• Status: Completed
• Conditions: Autism Spectrum Disorders
• Intervention / Treatment: Drug: Tideglusib; Other: Placebo

Detailed Description

There are no pharmacologic treatments available for social function deficits in individuals with Autism Spectrum Disorders (ASD). The data for pharmacologic treatment of repetitive behaviours in this disorder has also become difficult to interpret given that the last two large multisite trials of selective serotonin re-uptake inhibitors (SSRIs) in autism are reported to be negative for the treatment of repetitive behaviours. Only the associated symptom of irritability has 2 drugs with Food and Drug Administration (FDA) indications, whereas no systematic data exists on the pharmacologic treatment of anxiety in ASD, and response rates to stimulants for hyperactivity are lower than what is seen in Attention Deficit Hyperactivity Disorder (ADHD). In addition, there are no biological markers of treatment response identified in this population at this point. This study will examine the potential efficacy and safety of tideglusib for core and associated symptom domains of autism, and will explore biological markers of safety and treatment response. As there is no juvenile toxicity published in the animal model, we will limit the age range to 12 years of age and older.

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8S 4K1
      • McMaster University, Offord Centre for Child Studies
    • London, Ontario, Canada, N6A 5W9
      • University of Western Ontario, Lawson Health Research Institute
    • Toronto, Ontario, Canada, M4G 1R8
      • Holland Bloorview Kids Rehabilitation Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Outpatients 12-17 years of age inclusive with a mental age equivalent ≥ 18 months at Screening.
2. Weigh a minimum of 30 kg (the 3rd percentile for 12 years of age)
3. Meet Diagnostic and Statistical Manual of Mental Disorders. Diagnostic and Statistical Manual (DSM-5) criteria will be established by a clinician with expertise with individuals with ASD.
4. Have a Clinician's Global Impression-Severity (CGI-S) score ≥ 4 (moderately ill) at Screening.
5. If already receiving stable concomitant medications affecting behaviour, have stable regimens with no changes during the preceding 1 month prior to Screening (with the exception of fluoxetine, where a period of 6 weeks is needed), and will not electively initiate new or modify ongoing medications for the duration of the study
6. If already receiving stable non-pharmacological educational and behavioural interventions, have continuous participation during the preceding 3 months prior to Screening, and not electively initiate new or modify ongoing interventions for the duration of the study
7. Have normal physical examination and laboratory test results at Screening. If abnormal, the finding(s) must be deemed clinically insignificant by the Investigator.
8. Ability to obtain written informed consent from the participant, if developmentally appropriate. If a participant does not have the capacity to consent, ability to obtain assent (if developmentally appropriate), as well as written informed consent from their parent(s)/legal guardian.

Exclusion Criteria:

1. Patients with a primary psychiatric diagnosis other than ASD
2. Pregnant female patients; sexually active female patients on inadequate birth control.
3. Patients with known phosphatase and tensin homolog (PTEN) mutations as they are unlikely to respond to this medication
4. Patients with a serious medical condition that, based on Investigator judgment, might interfere with the conduct of the study, confound interpretation of the study results, or endanger their own well-being. Patients with evidence of any significant hematological, endocrine, cardiovascular (including uncorrected symptomatic congenital heart disease), respiratory, renal, hepatic, or gastrointestinal disease, not including mild common pediatric diseases in these areas that are stable (e.g. mild asthma, constipation, etc.).
5. Patients with unstable epilepsy (i.e. seizures occurring within the last 6 months), or patients with epilepsy who are not on stable doses of antiepileptic medications (i.e. dose changes within the last 3 months).
6. Patients with hypersensitivity to tideglusib or any components of its formulation.
7. Patients unable to tolerate venipuncture procedures for blood sampling.
8. Patients actively enrolled in another intervention study.
9. Patients who have elevated liver enzymes ≥ 3 times the normal amount before the study begins.
10. Patients who have serum creatinine of >150 μmol/L and creatinine clearance ≤60ml/m (according to Cockcroft-Gault formula) at Screening.
11. Patients taking strong CYP3A4 inhibitors (e.g. clarithromycin, telithromycin, ketoconazole, itraconazole, posaconazole, nefazodone, indinavir, ritonavir)
12. Inability to speak and understand English sufficiently enough to allow for the completion of all study assessments (parent; patient, if verbal).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Administered orally after dispersion in approximately 100 ml of water
Active Comparator: Tideglusib	Drug: Tideglusib; Administered orally after dispersion in approximately 100 ml of water at dose levels of 400 to 1000 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of tideglusib vs. placebo on measures of social engagement/withdrawal	This will be measured by the Aberrant Behavior Checklist (ABC) - Lethargy / Social Withdrawal Subscale	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of tideglusib vs. placebo on measures of repetitive behaviours	This will be measured by the Child Yale-Brown Obsessive Compulsive Scale (CY-BOCS)	12 weeks
Efficacy of tideglusib vs. placebo on measures of repetitive behaviours	This will be measured by the Repetitive Behavior Scale (RBS-R)	12 weeks
Efficacy of tideglusib vs. placebo on measures of social function	This will be measured by the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) - Socialization Domain	12 weeks
Safety and tolerability of tideglusib in adolescents with ASD	This will be measured by the Clinical Global Impressions - Improvement Scale - Global (CGI-I-Global)	12 weeks
Safety and tolerability of tideglusib in adolescents with ASD	This will be measured by the Safety Monitoring Uniform Report Form (SMURF)	12 weeks
Pharmacokinetic (PK) parameters in this age group	This will be completed by measuring / calculating Cmax (Peak Plasma Concentration)	12 weeks
Pharmacokinetic (PK) parameters in this age group	This will be completed by measuring / calculating C0-6 (Steady State Plasma Concentration)	12 weeks
Pharmacokinetic (PK) parameters in this age group	This will be completed by measuring / calculating Area Under the Curve (AUC)	12 weeks

Collaborators and Investigators

• Sponsor: Evdokia Anagnostou
• Collaborators: McMaster University; Unity Health Toronto; University of Toronto; University of Western Ontario, Canada; Holland Bloorview Kids Rehabilitation Hospital
• Investigators: Principal Investigator: Evdokia Anagnostou, M.D., Holland Bloorview Kids Rehabilitation Hospital; Principal Investigator: Robert Nicolson, M.D., University of Western Ontario, Lawson Health Research Institute; Principal Investigator: Terry Bennett, M.D., MacMaster University, Offord Centre for Child Studies

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2016
• Primary Completion (Actual): February 25, 2018
• Study Completion (Actual): February 25, 2018

Study Registration Dates

• First Submitted: October 16, 2015
• First Submitted That Met QC Criteria: October 23, 2015
• First Posted (Estimate): October 27, 2015

Study Record Updates

• Last Update Posted (Actual): May 31, 2018
• Last Update Submitted That Met QC Criteria: May 29, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: ASD; Autism
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive
• Other Study ID Numbers: TIDE-06-2015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No