Cariprazine in the Treatment of Pediatric Patients With Irritability Associated With Autism Spectrum Disorder: A Randomized Controlled Trial

Objective To evaluate the efficacy and safety of cariprazine in youth with irritability associated with autism spectrum disorder (ASD). Method This 8-week, multicenter, randomized, double-blind, controlled trial compared age- and weight-dependent flexibly-dosed cariprazine (0.75–3 mg/day) versus placebo in youth (5–17y) with ASD and irritability. The primary efficacy endpoint was week 8 change from baseline in caregiver-rated Aberrant Behavior Checklist–Irritability subscale (ABC–I) score. The first key secondary endpoint was the week 8 proportion of participants who were responders for clinician-rated Clinical Global Impressions–Change (CGI–C) in irritability ("much improved" or "very much improved"). Results 155 participants (mean age 10.6y, 70% male participants) received ≥1 study dose; 152 had baseline and ≥1 postbaseline ABC–I or CGI–C scores (n=74 cariprazine, n=78 placebo), with 81% completing the treatment period and 3.9% discontinuing due to treatment-emergent adverse events (TEAEs). The cariprazine group had significantly greater week 8 ABC–I improvement than placebo (least square mean difference [95% CI] = -3.7 [-6.75, -0.57], Cohen's d effect size=0.42, p = 0.0205). A significantly greater percentage of cariprazine-treated participants were CGI–C Irritability responders at week 8 than placebo (68.9% vs. 38.0%, odds ratio [95% CI] = 3.6 [1.7, 7.8], p = 0.0012). Overall, 51% of participants had TEAEs (1.3% had severe TEAEs); most commonly, somnolence and headache. TEAEs, laboratory values, and vital signs were consistent with cariprazine's known adult safety profile. Conclusion Pediatric patients with ASD treated with cariprazine demonstrated significantly greater improvement in irritability than placebo.