Clinical trial NCT02586935: Tideglusib vs. Placebo in the Treatment of Adolescents With Autism Spectrum Disorders
Official title: A Randomized Placebo-controlled Trial of Tideglusib vs. Placebo in the Treatment of Adolescents With Autism Spectrum Disorders (ASD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Autism Spectrum Disorders
Keywords: ASD
Autism
Lead sponsor: Anagnostou, Evdokia, M.D.
Sponsor class: INDIV
Collaborators: name: Holland Bloorview Kids Rehabilitation Hospital
name: McMaster University
name: University of Western Ontario, Canada
name: Unity Health Toronto
name: University of Toronto
First posted: 2015-10-27
Enrollment: 83
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Effect of tideglusib vs. placebo on measures of social engagement/withdrawal
timeFrame: 12 weeks
Secondary outcomes:
measure: Efficacy of tideglusib vs. placebo on measures of repetitive behaviours
timeFrame: 12 weeks
measure: Efficacy of tideglusib vs. placebo on measures of repetitive behaviours
timeFrame: 12 weeks
measure: Efficacy of tideglusib vs. placebo on measures of social function
timeFrame: 12 weeks
measure: Safety and tolerability of tideglusib in adolescents with ASD
timeFrame: 12 weeks
measure: Safety and tolerability of tideglusib in adolescents with ASD
timeFrame: 12 weeks
measure: Pharmacokinetic (PK) parameters in this age group
timeFrame: 12 weeks
measure: Pharmacokinetic (PK) parameters in this age group
timeFrame: 12 weeks
measure: Pharmacokinetic (PK) parameters in this age group
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: McMaster University, Offord Centre for Child Studies
state: Ontario
city: London
country: Canada
facility: University of Western Ontario, Lawson Health Research Institute
state: Ontario
city: Toronto
country: Canada
facility: Holland Bloorview Kids Rehabilitation Hospital
state: Ontario
Study officials:
affiliation: Holland Bloorview Kids Rehabilitation Hospital
name: Evdokia Anagnostou, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: MacMaster University, Offord Centre for Child Studies
name: Terry Bennett, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Western Ontario, Lawson Health Research Institute
name: Robert Nicolson, M.D.
role: PRINCIPAL_INVESTIGATOR
References: