Lumateperone for Irritability in Autism

Recruiting at 29 trial locations

Overseen By ITI Clinical Trials

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Intra-Cellular Therapies, Inc.

Must be taking: ADHD medications

Disqualifiers: Rett syndrome, Fragile X, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

174 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a multicenter, randomized, double-blind, placebo-controlled study in pediatric patients aged 5 to 17 years with a primary diagnosis of irritability associated with Autism Spectrum Disorder (ASD) based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition Text Revision (DSM-5-TR) and confirmed by the Kiddie Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version (K-SADS-PL).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are taking medication for ADHD, you must be on a stable treatment plan for 30 days before the trial and continue it during the study.

How is the drug Lumateperone unique for treating irritability in autism?

Lumateperone is unique because it is being explored specifically for irritability in autism, a condition with limited approved treatments. Unlike other drugs like aripiprazole and risperidone, which are already approved for irritability in autism, Lumateperone may offer a different mechanism of action, potentially providing an alternative option for patients who do not respond well to existing medications. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for children aged 5 to 17 with irritability linked to Autism Spectrum Disorder (ASD), as defined by the DSM-5-TR and confirmed by K-SADS-PL. Specific eligibility details are not provided, but typically include a clear ASD diagnosis and stable health.

Inclusion Criteria

CGI-S score > 4 with respect to irritability associated with ASD at Screening and Baseline

I am between 13 and 17 years old.

All patients must have an LAR (eg, parent or legal guardian) who is willing and able to be responsible for the safety and well-being of the patient, provide information about the patient's condition, and accompany the patient to study visits

Exclusion Criteria

I have a psychiatric condition other than ASD, but ADHD is allowed if my treatment has been stable for 30 days.

History or current diagnosis of Rett syndrome or Fragile X syndrome

Mild and moderate intellectual disability based on Investigator judgment and DSM-5 criteria (severe and profound intellectual disability are excluded)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Double-blind Treatment

Participants are randomized to receive either lumateperone high dose, lumateperone low dose, or placebo once daily for 6 weeks

6 weeks

Safety Follow-up

Participants return to the clinic for a safety follow-up visit approximately 1 week after the last dose of study drug

1 week

Treatment Details

Interventions

• Lumateperone

Trial Overview The study tests Lumateperone at high and low doses against a placebo in pediatric patients. It's randomized, meaning participants are assigned randomly to one of these treatments, and double-blind, so neither the researchers nor participants know who gets what.

Participant Groups

Group I: Lumateperone low dose Experimental Treatment 1 Intervention

Lumateperone 21 mg for patients ages 13-17 years old

Group II: Lumateperone high dose Experimental Treatment 1 Intervention

Lumateperone 42 mg for patients ages 13-17 years old

Group III: Placebo Placebo Group 1 Intervention

Placebo

Lumateperone is already approved in United States for the following indications:

Approved in United States as Caplyta for:

• Schizophrenia
• Bipolar I or II disorder (bipolar depression)

Who Is Running the Clinical Trial?

Intra-Cellular Therapies, Inc.

Lead Sponsor

Trials

42

Recruited

10,700+

Findings from Research

In a study of 45 children and adolescents with autism spectrum disorders, low-dose liquid fluoxetine was found to be more effective than placebo in reducing repetitive behaviors, with a moderate to large effect size.

Liquid fluoxetine did not show significant differences in side effects compared to placebo, indicating it may be a safe option for treating repetitive behaviors in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A placebo controlled crossover trial of liquid fluoxetine on repetitive behaviors in childhood and adolescent autism. Hollander, E., Phillips, A., Chaplin, W., et al.[2022]

Risperidone and aripiprazole are the most supported pharmacological treatments for irritability in autism, with multiple randomized controlled trials (RCTs) showing significant improvements in symptoms.

While several alternative treatments like clonidine and methylphenidate also showed efficacy, they are less established than the FDA-approved antipsychotics, highlighting the need for behavioral therapy alongside medication for optimal management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of the pharmacotherapy of irritability of autism. Elbe, D., Lalani, Z.[2021]

Aripiprazole is one of the few medications approved in the USA for treating irritability in individuals with autism spectrum disorder (ASD), showing clear benefits in multiple studies compared to placebo.

While effective, aripiprazole can have metabolic side effects, highlighting the importance of monitoring and periodic reassessment of treatment needs for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aripiprazole for treating irritability associated with autism spectrum disorders. Bartram, LA., Lozano, J., Coury, DL.[2019]

In a 14-week study involving 25 children and adolescents with PDD-NOS or Asperger's disorder, aripiprazole significantly reduced irritability symptoms, with 88% of participants showing improvement.

Aripiprazole was well tolerated, with only mild side effects reported, and no participants left the study due to drug-related adverse events, suggesting it is a safe option for managing irritability in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aripiprazole in pervasive developmental disorder not otherwise specified and Asperger's disorder: a 14-week, prospective, open-label study. Stigler, KA., Diener, JT., Kohn, AE., et al.[2021]

MPEP, an mGluR5 receptor antagonist, effectively reduced repetitive self-grooming behaviors in BTBR mice, a model for autism, without causing sedation, suggesting its potential as a targeted treatment for such behaviors.

Risperidone also decreased repetitive self-grooming in BTBR mice, but only at sedating doses, indicating that while it may help with certain symptoms, it could also lead to unwanted side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive self-grooming behavior in the BTBR mouse model of autism is blocked by the mGluR5 antagonist MPEP. Silverman, JL., Tolu, SS., Barkan, CL., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

A placebo controlled crossover trial of liquid fluoxetine on repetitive behaviors in childhood and adolescent autism. [2022]

2. Canada pubmed.ncbi.nlm.nih.gov

Review of the pharmacotherapy of irritability of autism. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Aripiprazole for treating irritability associated with autism spectrum disorders. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Aripiprazole in pervasive developmental disorder not otherwise specified and Asperger's disorder: a 14-week, prospective, open-label study. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Repetitive self-grooming behavior in the BTBR mouse model of autism is blocked by the mGluR5 antagonist MPEP. [2022]