Positive results from an international phase 3 trial investigating a novel delivery system of asenapine for the treatment of schizophrenia in adults (ClinicalTrials.gov Identifier: NCT02876900) were announced at Psych Congress 2019, held October 3 to 6 in San Diego, California. Well tolerated, the HP-3070 transdermal asenapine patch represents an efficacious delivery system with a similar systemic safety profile to sublingual asenapine.
The fixed-dose inpatient study included 616 adult patients (373 male) experiencing acute exacerbation of schizophrenia. These eligible patients were adults with screening and a baseline Positive and Negative Syndrome Scale (PANSS) total score of 280 with scores of 24 on at least 2 of 4 predefined PANSS positive subscale items and a Clinical Global Impression-Severity of Illness Scale (CGI-S) score of 24, and who were able to wear a patch for 24 hours. The primary efficacy endpoint was change from baseline (CFB) in PANSS total score at week 6; secondary efficacy endpoint was CFB in CGI-S score at week 6.
At 59 participating centers in the United States, Bulgaria, Russia, Serbia, and Ukraine, patients were randomly assigned to low-dose HP-3070 (n=204), high-dose HP-3070 (n=204), or placebo (n=206). Low-dose and high-dose HP-3070 patches were designed to be equivalent in terms of overall medication exposures to sublingual asenapine 5 and 10 mg twice daily, respectively. A 6-week double-blind treatment period and 30-day follow-up began after the initial screening and washout period of 3 to 14 days. Patients who presented with their first episode of schizophrenia, were known nonresponders to asenapine, or were resistant/refractory to antipsychotic treatment were excluded from the study.
Results demonstrated that both doses of HP-3070 resulted in significantly greater improvements vs placebo (Hochberg adjusted P <.05). For PANSS total scores, significant differences compared with placebo were observed for low-dose HP-3070 (P <.05) beginning at week 2, and for high-dose HP-3070 (P <.05) at weeks 3, 5, and 6.
For CGI-S scores, significant differences compared with placebo were observed for both doses of HP-3070 beginning at week 2 (P <.01 and P <.05, respectively).
Between 52% and 55% of patients reported treatment-emergent adverse events (TEAEs), and most were mild or moderate and occurred at the patch application site. A total of 7 patients (3.4%), 3 patients (1.5%), and 5 patients (2.4%) in the high-dose, low-dose, and placebo groups, respectively, experienced severe TEAEs. Those TEAEs leading to discontinuation included nervous system disorders (eg, akathisia, extrapyramidal disorder), which were more common in patients receiving HP-3070, and psychiatric disorders (eg, schizophrenia, insomnia), which were more common in patients receiving placebo. The most frequently reported TEAEs in patients who received HP-3070 were nervous system disorders, and in patients who received placebo were psychiatric disorders.
The discontinuation rate was 22.5%, 18.6%, and 21.4% for high-dose HP-3070, low-dose HP-3070, and placebo groups, respectively. In addition, at week 6, an increase of at least 7% in body weight was observed in 14.3% and 18.3% of patients receiving high- and low-dose HP-3070, respectively, and in 3.9% of patients receiving placebo.
HP-3070 may provide several advantages over sublingual asenapine, the researchers noted, including “reduced risk of oral hypoesthesia and dysgeusia, lack of food or drink restrictions, and steadier absorption and plasma levels of asenapine.” A number of unmet needs in patients with psychiatric illnesses, such as reduced dosing frequency, effective control of medication plasma concentrations, improved adherence to therapy, reduced potential for drug-drug interactions, improved tolerability (eg, decreased gastrointestinal irritation), ability to check compliance visually, and avoidance of first-pass hepatic metabolism, the investigators wrote, may be filled through use of the HP-3070 transdermal administrator.
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Disclosure: This research was supported by Novan Pharmaceuticals, Inc. Please see the original references for a full list of authors’ disclosures.
Citrome L, Walling D, Zeni C, et al. Efficacy and safety of an asenapine transdermal system (HP-3070) for treatment of adults with schizophrenia: a Phase 3 randomized, placebo-controlled, inpatient study. Presented at: Psych Congress 2019; October 3-6, 2019; San Diego, CA. Poster 122.