Main LAP01 study: The purpose is to evaluate the long-term pathologic weight changes associated with multi-year risperidone or aripiprazole therapy in 3 - <18-year-old children, who have varying durations of prior antipsychotic drug exposure from the start of study Month 0 (M0). This is critical because children appear to have greater vulnerability to antipsychotic-associated weight gain than adults, and obesity has significant effects on morbidity and mortality.

An additional sub-study (registry sub-study) was added via a protocol amendment. This registry sub-study is optional for participants and only participants who participate in the main study are eligible if they were 6 to less than 18 years of age at the time of the M0 visit. Participants who consent to this registry sub-study will participate in yearly in-person visits and complete monthly assessments remotely over the course of two additional years from the time of their final visit of the main LAP01 study.

Main LAP01 study: Prospective, multi-site, Phase 4, longitudinal observational study designed to systematically collect robust longitudinal post-marketing safety and quality of life data about multi-year pediatric treatment with risperidone or aripiprazole. Screening may occur for up to 37 days prior to enrollment. Assessments will occur at in-person visits planned at months 0, 6, 12, 18 and 24, and at unscheduled, in-person visits that study staff request when the participant switches or stops antipsychotic monotherapy with risperidone or aripiprazole, adds or stops treatment with a weight modifying agent, becomes pregnant, chooses to withdraw from the study prematurely or, has an ongoing Serious Adverse Event (SAE) that requires further assessment. Monthly remote interim contacts occurring between in-person visits will monitor for changes (other than dose related) in antipsychotic therapy or weight modifying treatments, potential SAEs, and potential pregnancy. The participant, his/her parent/guardian, and the participant's personal psychotropic-prescribing medical provider (PPPMP) will make any and all decisions related to antipsychotic medications, any other medications, and the participant's current mental state, developmental/psychiatric condition, and level of risk for potential harm to self or others independent of the study procedures and assessments. Study staff (SS) will share with the participant's PPPMP all lab results and changes in the participant's AEs or clinical presentation, which the study medical clinician (SMC) considers medically concerning based on the participant's assessment during in-person visits. If an emergency safety concern is evident during an in-person visit, the SMC will immediately assess the participant, following medical standard-of-care procedures, to determine whether the participant is safe to leave the clinic or requires additional emergency care. If new or worsening symptoms are reported by the participant or parent/guardian during remote interim contacts, the participant and/or parent/guardian will be instructed to contact the PPPMP directly.

Registry sub-study: Participants who choose to participate will consent via a mobile application (Pattern Health) and will measure their height and weight at home monthly (also collected through the Pattern Health mobile application). One questionnaire will be completed every 6 months via the Pattern Health mobile application. Yearly in-person visits will be conducted to obtain in-clinic height, weight, vital signs and review concomitant medications.

Main Study

Inclusion Criteria:

1. Parent/guardian has provided informed consent

2. Participant has provided assent if developmentally appropriate and as required by the institutional review board (IRB)

3. 3 - <18 years of age inclusive at time of M0 visit

4. Participant, when developmentally appropriate, and parent/guardian are:

   1. Willing to authorize exchange of information between the SS and the participant's PPPMP and/or other significant medical provider
   2. Affirm participant's use at M0 visit of either risperidone or aripiprazole mono-antipsychotic therapy as prescribed by participant's PPPMP

5. Based on their age at the time of M0 visit, participant is receiving aripiprazole or risperidone at the dose and for the diagnoses as listed below:

   1. Participants ages 3 - < 6 years can have any diagnosis and any dose

   2. Participants ages ≥ 6 - <18 years at the doses and for the diagnoses listed below

      Labeled Indications (Closely Related Disorders)

      Aripiprazole 2-30 mg/day

      • Irritability associated with autistic disorder:

      (Irritability in autism spectrum disorder) - Treatment of Tourette's disorder: (Tourette's disorder, persistent (chronic) motor or vocal tic disorder)

      - Bipolar mania/acute treatment of manic and mixed episodes associated with Bipolar l disorder: (Bipolar spectrum disorders including disruptive mood dysregulation disorder)

      - Schizophrenia: (Schizophrenia spectrum disorders including schizoaffective disorder, psychosis not otherwise specified, and delusional disorder)

      Risperidone 0.25-6 mg/day - Irritability associated with autistic disorder: (Irritability in autism spectrum disorder)

      - Bipolar Mania: (Bipolar spectrum disorders including disruptive mood dysregulation disorder)

      - Schizophrenia: (Schizophrenia spectrum disorders including schizoaffective disorder, psychosis not otherwise specified, and delusional disorder)

      • MYCITE® (aripiprazole) and all forms of injectables are not permitted in this study

6. Guardian anticipates risperidone or aripiprazole treatment will continue for ≥6 months

Exclusion Criteria:

1. History of prior or current diagnosis of an eating disorder or meets diagnostic criteria for an eating disorder as described in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and determined by psychiatric exam
2. Pre-existing or suspected major medical, metabolic, or genetic condition that is expected to be associated with weight, cardiovascular, neuromotor, or endocrine problems
3. Known or self-reported pregnancy
4. Taking antipsychotic medication other than either risperidone or aripiprazole at the time of M0 visit
5. Contraindications to participation in the study in the opinion of the SMC
6. Unwilling or unable to provide back-up family contact information

Registry Sub-Study

Inclusion Criteria:

1. Enrolled in LAPS Trial
2. Access to a personal mobile device (with Bluetooth capability and data or internet access) and willing to use it for the purposes of this study
3. Parent/guardian/LAR/participant has provided informed consent
4. Participant has provided assent/consent if developmentally appropriate and as required by the institutional review board (IRB)
5. Participant was part of the 6 to <18 year-old group in the LAPS Trial

Exclusion Criteria:

1. Participant has completed the M24 LAPS Trial Visit

Main Study:

The study population will consist of two groups of children 3 - <18 yrs old at the M0 visit:

• Risperidone group, n=350, including 30 children 3 - <6 yrs old and 320 children 6 - <18 yrs old, ~ 50% - 80% will have <90 days of prior treatment with any antipsychotic.
• Aripiprazole group, n=350, including 30 children 3 - <6 yrs old and 320 children 6 - <18 yrs old., ~ 50% - 80% will have ≤90 days of prior treatment with any antipsychotic.

We will target participants within each treatment group to be distributed across the age range to permit analyses of age effects with:

• ~30 being 3 - <6 years
• ≥35% (n ≥123) being 6 - <12 years
• ≥35% (n ≥123) being 12 - <18 years PK sub group at selected sites includes 24 participates, details in protocol.

Registry Sub-Study Registry participants will be selected exclusively from the population that has enrolled onto the LAPS Trial.

All data collected is uploaded into the National Institute of Health data repository (DASH) at the end of the study (de-identified).

Data will be uploaded to the repository within 2 years of study completion. It will be maintained in the repository indefinitely.

In order to have access, researchers have to complete a Data access request. NICHD will review the request and either approve or deny it. IRB approval must be obtained by the researcher to access the data.

https://dash.nichd.nih.gov/Resource/DataRequestChecklist