Efficacy of HP-3070, an Asenapine Transdermal System, on Symptoms of Hostility in Adults With Schizophrenia: A Post Hoc Analysis of a 6-Week Phase 3 Study

Leslie Citrome, MD, MPH; Marina Komaroff, DrPH; Brittney Starling, PharmD; Sandeep Byreddy, MS; Takaaki Terahara, PhD; Masami Hasebe, MPharm

J Clin Psychiatry 2022;83(4):21m14355

ABSTRACT

Objective: Patients with schizophrenia may exhibit symptoms of hostility. HP-3070 is the first antipsychotic patch approved by the US Food and Drug Administration (FDA) for adults with schizophrenia. Its efficacy was demonstrated in a phase 3 study. This post hoc analysis assessed the efficacy of HP-3070 in treating hostility in schizophrenia.

Methods: In the pivotal phase 3 study, conducted between August 2016 and November 2017, adults with schizophrenia (per DSM-5 criteria) were randomized to HP-3070 3.8 mg/24 h, HP-3070 7.6 mg/24 h, or placebo. Least-squares mean (LSM) changes in Positive and Negative Syndrome Scale (PANSS) hostility item and PANSS–Excited Component (PANSS-EC) scores from baseline to week 6 were assessed post hoc using a mixed-effects model for repeated measures adjusted for selected PANSS-Positive symptoms and presence of somnolence or akathisia.

Results: Among 442 patients with baseline PANSS hostility item score > 1 (n = 151, HP-3070 7.6 mg/24 h; n = 147, 3.8 mg/24 h; n = 144, placebo), week 6 LSM (95% CI) change from baseline (CFB) in hostility score was superior with HP-3070 versus placebo for 7.6 mg/24 h (−0.4 [−0.6 to −0.2]; P < .001) and 3.8 mg/24 h (−0.3 [−0.6 to −0.1]; P < .01), with similar results for 7.6 mg/24 h after adjusting for covariates (P < .05). For all patients regardless of baseline PANSS hostility item score, PANSS-EC week 6 LSM CFB was greater for HP-3070 7.6 mg/24 h (−1.1 [−1.9 to −0.4]; n = 203; P < .01) and 3.8 mg/24 h (−1.3 [−2.0 to −0.6]; n = 201; P < .001) than for placebo (n = 203), with similar results observed in patients with baseline hostility item score > 1.

Conclusions: In this post hoc analysis, HP-3070 was superior to placebo in reducing schizophrenia-associated hostility, even after adjusting for covariates, suggesting these effects are at least partially independent of general antipsychotic effects or effects on sedation or akathisia. These findings suggest HP-3070 has a specific antihostility effect in patients with schizophrenia.

Clinical Trials Registration: ClinicalTrials.gov identifier: NCT02876900; EudraCT number: 2015–005134-21

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References (22)

Citrome L, Volavka J. Pharmacological management of acute and persistent aggression in forensic psychiatry settings. CNS Drugs. 2011;25(12):1009–1021. PubMed CrossRef
Citrome L, Volavka J. Specific anti-hostility effects of atypical antipsychotics in persons with schizophrenia: from clozapine to cariprazine. Harv Rev Psychiatry. 2021;29(1):20–34. PubMed CrossRef
Volavka J, Citrome L. Pathways to aggression in schizophrenia affect results of treatment. Schizophr Bull. 2011;37(5):921–929. PubMed CrossRef
Citrome L, Volavka J. The psychopharmacology of violence: making sensible decisions. CNS Spectr. 2014;19(5):411–418. PubMed CrossRef
The Joint Commission. R3 report issue 30: workplace violence prevention standards. June 18, 2021. The Joint Commission website. https://www.jointcommission.org/-/media/tjc/documents/standards/r3-reports/wpvp-r3-30_revised_06302021.pdf. Accessed February 11, 2022.
Kay SR, Opler LA, Fiszbein A, et al. Positive and Negative Syndrome Scale (PANSS) - Technical Manual. North Tonawanda, NY: Multi-Health Systems Inc; 2010.
Volavka J, Zito JM, Vitrai J, et al. Clozapine effects on hostility and aggression in schizophrenia. J Clin Psychopharmacol. 1993;13(4):287–289. PubMed CrossRef
Buckley P, Bartell J, Donenwirth K, et al. Violence and schizophrenia: clozapine as a specific antiaggressive agent. Bull Am Acad Psychiatry Law. 1995;23(4):607–611. PubMed
Rabinowitz J, Avnon M, Rosenberg V. Effect of clozapine on physical and verbal aggression. Schizophr Res. 1996;22(3):249–255. PubMed CrossRef
Citrome L, Du Y, Risinger R, et al. Effect of aripiprazole lauroxil on agitation and hostility in patients with schizophrenia. Int Clin Psychopharmacol. 2016;31(2):69–75. PubMed CrossRef
Czobor P, Volavka J, Meibach RC. Effect of risperidone on hostility in schizophrenia. J Clin Psychopharmacol. 1995;15(4):243–249. PubMed CrossRef
Citrome L, Pikalov A, Tocco M, et al. Effects of lurasidone on hostility in patients with an acute exacerbation of schizophrenia: a pooled post hoc analysis of 5 short-term studies. Eur Psychiatry. 2015;30(S1):249. CrossRef
Citrome L, Landbloom R, Wu X, et al. Effect of asenapine on measures of hostility in adults with bipolar I disorder or schizophrenia [poster]. Presented at Annual Meeting of the American Society of Clinical Psychopharmacology (ASCP). May 30–June 3, 2016; Scottsdale, AZ.
Secuado (asenapine) transdermal system [package insert]. Tosu, Japan: Hisamitsu Pharmaceutical Co, Inc; 2019.
Noven Pharmaceuticals, Inc. US FDA approves SECUADO (asenapine) transdermal system, the first-and-only transdermal patch for the treatment of adults with schizophrenia [press release]. October 15, 2019. Noven website. http://www.noven.com/wp-content/uploads/2020/02/PR101519-1.pdf. Accessed October 23, 2019.
Citrome L, Walling DP, Zeni CM, et al. Efficacy and safety of HP-3070, an asenapine transdermal system, in patients with schizophrenia: a phase 3, randomized, placebo-controlled study. J Clin Psychiatry. 2020;82(1):20m13602. PubMed
Lindenmayer JP, Brown E, Baker RW, et al. An excitement subscale of the positive and negative syndrome scale. Schizophr Res. 2004;68(2–3):331–337. PubMed CrossRef
Montoya A, Valladares A, Lizán L, et al. Validation of the Excited Component of the Positive and Negative Syndrome Scale (PANSS-EC) in a naturalistic sample of 278 patients with acute psychosis and agitation in a psychiatric emergency room. Health Qual Life Outcomes. 2011;9(1):18. PubMed CrossRef
Citrome L, Volavka J, Czobor P, et al. Efficacy of ziprasidone against hostility in schizophrenia: post hoc analysis of randomized, open-label study data. J Clin Psychiatry. 2006;67(4):638–642. PubMed CrossRef
Swanson JW, Swartz MS, Van Dorn RA, et al. A national study of violent behavior in persons with schizophrenia. Arch Gen Psychiatry. 2006;63(5):490–499. PubMed CrossRef
Kane JM, Cohen M, Zhao J, et al. Efficacy and safety of asenapine in a placebo- and haloperidol-controlled trial in patients with acute exacerbation of schizophrenia. J Clin Psychopharmacol. 2010;30(2):106–115. PubMed CrossRef
Potkin SG, Cohen M, Panagides J. Efficacy and tolerability of asenapine in acute schizophrenia: a placebo- and risperidone-controlled trial. J Clin Psychiatry. 2007;68(10):1492–1500. PubMed CrossRef