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LONG-TERM SAFETY AND TOLERABILITY OF CARIPRAZINE IN PEDIATRIC PATIENTS WITH AUTISM SPECTRUM DISORDER, BIPOLAR I DISORDER OR SCHIZOPHRENIA: FINAL RESULTS FROM AN OPEN-LABEL STUDY

Marshall B. Lucas — Diab Almhana2, Jeffery R. Strawn3, Robert Riesenberg4, Elaine Smith5, Amin Shirazi5, Lauren Aronin5, Shane Varughese5, Marc S. Weinberg5 1Family Psychiatry of The Woodlands, 2Quest Therapeutics of Avon Lake, 3University of Cincinnati and Cincinnati Children's Hospital Medical Center, 4Atlanta Center for Medical Research, 5AbbVie

2026 ASCP Annual Meeting

Background

Guidelines recommend atypical antipsychotics (AAs) as a first-line treatment option for early-onset bipolar I disorder (BP-I) and schizophrenia (SCZ). AAs are also used to treat irritability and aggression in children with autism spectrum disorders (ASD). However, fewer AAs are approved for pediatric use than for adults, and children may be more susceptible to antipsychotic-associated side effects (eg, weight gain, sedation, and extrapyramidal symptoms). Cariprazine, a dopamine D3-preferring D3/D2 receptor and serotonin 5-HT1A receptor partial agonist, is approved to treat both depressive and manic/mixed episodes of BP-I as well as SCZ in adults, and more recently approved to treat BP-I manic/mixed episodes and SCZ in children aged 10-17 and 13-17 years, respectively. Although cariprazine has a well-established risk-benefit profile in adults, it has yet to be fully characterized in pediatric patients. This study evaluated the long-term safety and tolerability of cariprazine for pediatric patients with ASD, BP-I or SCZ.

Methods

Patients aged 5-17 years with ASD, 10-17 years with BP-I, or 13-17 years with SCZ were enrolled in a 52-week, multicenter, open-label, flexible-dose phase 3 study (NCT04578756). Dosing was individualized by diagnosis, age, and body weight and ranged from 0.75 to 4.5 mg/d. Safety parameters included adverse events (AEs), extrapyramidal symptom scales (eg, the Barnes Akathisia Rating Scale [BARS] and Simpson–Angus Scale [SAS]), clinical laboratory measures, vital signs, electrocardiogram (ECG), and suicidality measures (via the Columbia-Suicide Severity Rating Scale [C-SSRS]). Data were analyzed using descriptive statistics.

Results

The safety population included 306 patients (ASD, n=139; BP-I, n=146; SCZ, n=21). Of these, 44% discontinued during the open-label treatment period, most commonly due to withdrawal by a parent/guardian (19%); approximately 8% discontinued due to an AE. Treatment-emergent AE (TEAEs) occurred in 67% of patients and were mostly mild or moderate. Serious TEAEs were reported by 4% of patients overall, and 40% of TEAEs were considered treatment-related by the investigator. Common TEAEs (≥5% for any indication) included weight increase (14%), headache (10%), somnolence (10%), nausea (9%), fatigue (7%), vomiting (7%), agitation (5%), akathisia (5%), insomnia (4%), anxiety (4%), salivary hypersecretion (2%) and dysmenorrhoea (2%). No clinically meaningful changes from baseline were observed in laboratory tests, vital signs or ECGs. A small, clinically nonsignificant increase in age-and gender-adjusted body weight was observed (mean z-score change=0.1). No increased suicidality was reported on the C-SSRS.

Conclusions

Long-term cariprazine treatment in pediatric patients was generally well tolerated with no new signals. Safety outcomes were largely similar across indications, supporting generalizability of the data across pediatric populations.