LAUSR

Abstract Background Patients with schizophrenia may exhibit symptoms of hostility. HP-3070, a once-daily asenapine transdermal system, is the first antipsychotic patch approved by the FDA for use in adults with schizophrenia, and its efficacy in this indication has been demonstrated. This post hoc analysis of a phase 3 randomized study investigated the efficacy of HP-3070 in treating hostility in patients with schizophrenia. Methods In the pivotal phase 3 study, adults with schizophrenia were randomized 1:1:1 to once-daily treatment with HP-3070 3.8 mg/24 h, 7.6 mg/24 h, or placebo for 6 weeks. Least-squares mean (LSM) changes in the PANSS hostility item score (P7) and PANSS-Excited Component (PANSS-EC), the sum of items P4 (Excitement), P7 (Hostility), G4 (Tension), G8 (Uncooperativeness), and G14 (Poor impulse control), from baseline to week 6 were assessed post hoc. Efficacy was analyzed with a mixed-effects model for repeated measures (MMRM) adjusted for PANSS-positive symptoms, items P1 (Delusions), P2 (Conceptual disorganization), P3 (Hallucinatory behavior), P5 (Grandiosity), P6 (Suspiciousness/persecution), and G9 (Unusual thought content) and presence of somnolence (including hypersomnia, hypersomnolence, or sedation) or akathisia. Results Among the 369 patients with a baseline PANSS hostility item score >1 and hostility scores collected at both baseline and week 6 (126 HP-3070 7.6 mg/24 h; 123 3.8 mg/24 h; 120 placebo), the week 6 LSM (95% CI) change from baseline in PANSS hostility item score was significantly better with HP-3070 than placebo for 7.6 mg/24 h (−0.4 [−0.6, −0.2]; P < .001) and 3.8 mg/24 h (−0.3 [−0.6, −0.1]; P < .01). Similar results were observed after adjusting for covariates (P < .01 for both doses). The week 6 PANSS-EC LSM change from baseline was also greater for HP-3070 7.6 mg/24 h (−1.1 [−1.9, −0.4]; n = 164; P < .01) and 3.8 mg/24 h (−1.3 [−2.0, −0.6]; n = 168; P < .001) compared with placebo (n = 165). Conclusions In this post hoc analysis, HP-3070 was superior to placebo in reducing hostility in patients with schizophrenia, even after adjusting for covariates, suggesting that these effects are at least partially independent of general antipsychotic effects or of effects on sedation or akathisia. These findings suggest that HP-3070 may have a specific anti-hostility effect in patients with schizophrenia. Funding Noven Pharmaceuticals, Inc., a wholly-owned subsidiary of Hisamitsu Pharmaceutical, Co.